Cobbers on the Brain – Student Commentary on the Neurological Sciences

Understanding Schizophrenia: A Complex Interplay of Genetics, Wnt Signaling, and Treatment

Posted on March 26, 2025 by jdeitz1 / 0 Comment

Schizophrenia is a puzzle—a complex and often misunderstood disorder that disrupts lives in profound ways. For decades, scientists have worked to piece together its causes, searching for answers in genetics, brain development, and molecular pathways like Wnt signaling. While progress has been made, effective treatment remains a challenge, leaving researchers to dig deeper into the intricate ways Wnt signaling influences schizophrenia. [1] Could understanding this pathway provide new hope for treatment?

Artstract created by J. Deitz

The Role of Wnt Signaling in the Brain

Imagine the brain as a carefully choreographed symphony, with different pathways ensuring that each instrument plays in harmony. Wnt signaling is one such conductor, orchestrating key aspects of neurodevelopment. It guides the formation of the brain’s anterior-posterior axis, shapes early patterning events like the midbrain and spinal cord development, and maintains neural stem cell populations. Without it, the music falters—cells exit the cycle too soon, leading to stunted neuron development and widespread disruption. [2]

In schizophrenia, disruptions in Wnt signaling have been linked to abnormalities in brain structure and function. The delicate balance of neural communication is thrown off, affecting cognition, perception, and behavior. If Wnt signaling is so vital, could restoring its function alleviate some of the symptoms of schizophrenia? Scientists are eager to find out.

Genetic Factors and Their Influence on Schizophrenia

Genetics tell another part of the story. Certain genes have been identified as potential risk factors, each playing a different role in brain development and function. DISC1, for example, is a key player in neurodevelopment and Wnt signaling, while Akt influences cell survival and neural connectivity. Variants in genes like LRP1, DAB2IP, and PIK3CB have also been linked to schizophrenia, particularly in families with a history of the disorder. [1]

The timing of brain development appears to be just as important as genetic predisposition. Childhood-onset schizophrenia (COS) presents a more severe and genetically influenced form of the disorder, suggesting that early developmental windows may shape symptom severity. Understanding the genetic blueprint of schizophrenia not only helps in predicting the disorder but could also be the key to more targeted treatments. [3]

Wnt Signaling and Schizophrenia Treatment

If Wnt signaling plays a role in schizophrenia, then targeting this pathway could offer new therapeutic possibilities. Some existing treatments already hint at this connection. Antipsychotic drugs primarily target dopamine pathways, but some also interact with Wnt signaling, particularly through D2 receptors. Lithium, a well-known mood stabilizer, is believed to enhance Wnt signaling, offering potential benefits for schizophrenia patients. [1]

Despite these promising connections, treatment responses vary widely. What works for one patient may not work for another, highlighting the urgent need for personalized medicine. By understanding the molecular profiles of individuals with schizophrenia, scientists hope to tailor treatments more effectively, ensuring that each person receives the care best suited to their needs.

Animal Models and Future Research

Studying schizophrenia in humans is complex, so researchers often turn to animal models for clues. While no animal model can fully replicate schizophrenia, certain behaviors and brain changes linked to Wnt signaling provide valuable insights. However, these models have limitations, and findings must be interpreted with caution. Moving forward, refining these models to better mimic human schizophrenia could be a game-changer in research and drug development. [1]

Conclusion

Schizophrenia is not just one disorder—it is a spectrum of experiences shaped by genetics, brain chemistry, and environmental factors. The Wnt signaling pathway, once thought to be a niche area of study, has emerged as a major player in understanding schizophrenia’s complexities. While current treatments mainly focus on dopamine regulation, a deeper understanding of Wnt signaling could open new doors to personalized therapies and better patient outcomes. The puzzle is far from complete, but with continued research, the pieces are slowly coming together.

To read more about schizophrenia and its link to Wnt signaling, click here.

[1] Singh, “An emerging role for Wnt and GSK3 signaling pathways in schizophrenia,” Clinical Genetics, vol. 83, no. 6, pp. 511–517, Jun. 2013, doi: 10.1111/cge.12111.

[2] Noelanders and K. Vleminckx, “How Wnt Signaling Builds the Brain: Bridging Development and Disease,” Neuroscientist, vol. 23, no. 3, pp. 314–329, Jun. 2017, doi: 10.1177/1073858416667270.

[3] Gogtay, N. S. Vyas, R. Testa, S. J. Wood, and C. Pantelis, “Age of Onset of Schizophrenia: Perspectives From Structural Neuroimaging Studies,” Schizophrenia Bulletin, vol. 37, no. 3, pp. 504–513, May 2011, doi: 10.1093/schbul/sbr030.

Uncategorized

Types Of Antipsychotic Medications

Posted on March 26, 2025 by tchilala / 0 Comment

Why Should the Public Care About Antipsychotic Medications?

Antipsychotic medications are a crucial part of psychiatric treatment, helping millions of people manage severe mental health conditions such as schizophrenia and bipolar disorder. Understanding how these drugs work and their impact on brain chemistry is essential for reducing stigma, improving treatment outcomes, and fostering scientific advancements in mental health care. With emerging research linking antipsychotic drugs to complex biochemical pathways like Wnt and GSK3 signaling, the public must stay informed about potential breakthroughs that could lead to more effective and targeted therapies.

Summary of the Science: Wnt and GSK3 Signaling in Schizophrenia

Schizophrenia is a chronic psychiatric disorder that affects brain development and neural connectivity. Despite available treatments, the precise biological mechanisms underlying schizophrenia remain unclear. The article An Emerging Role for Wnt and GSK3 Signaling Pathways in Schizophrenia explores the role of these signaling pathways in the disorder.[1]

Wnt signaling is a crucial pathway in brain development and function. It regulates neural circuit formation, synaptic plasticity, and overall brain health. The research highlights how disruptions in Wnt and glycogen synthase kinase 3 (GSK3) signaling contribute to schizophrenia pathophysiology.

Current antipsychotic drugs, including clozapine and haloperidol, interact with these pathways, affecting dopamine signaling and modulating GSK3 activity. Notably, lithium, a common mood stabilizer, directly inhibits GSK3, potentially stabilizing Wnt signaling and improving psychiatric symptoms.

Fig. 1. Wnt signaling pathways. There are three main Wnt signaling pathways: (a) canonical Wnt signaling, (b) Wnt-calcium signaling and (c) non-canonical Wnt/planar cell polarity signaling.

Fig. 2. Psychiatric disease pathways impinge upon glycogen synthase kinase 3 signaling networks. Diagram illustrating how human genetic findings, pharmacological drug treatments directly or indirectly influence canonical and non-canonical Wnt signaling pathways.

Bridging Antipsychotics and Advanced Research

One of the most compelling aspects of this research is the intersection between dopamine and Wnt signaling. Dopamine dysregulation has long been associated with schizophrenia, and emerging findings suggest that Wnt-related mechanisms may further modulate these effects. Studies indicate that D2 dopamine receptor antagonists, a class of antipsychotics, inhibit GSK3, thereby stabilizing β-catenin, a key component in Wnt signaling (Figure 2). This interaction offers a deeper understanding of how psychiatric medications function beyond dopamine receptor blockade.[3]

Medication	Usage	Benefits	Side Effects

Haloperidol (Haldol)

Used to treat schizophrenia, acute psychosis, and severe agitation. Also used for Tourette syndrome and nausea in some cases.

– Rapid control of acute psychotic symptoms.
– Effective in managing severe agitation and hallucinations.
– Available in oral, injectable, and long-acting forms.

– Extrapyramidal symptoms (EPS) such as dystonia, akathisia, and parkinsonism.
– Tardive dyskinesia with long-term use.
– Increased risk of neuroleptic malignant syndrome (NMS).
– Sedation and low blood pressure.

Clozapine

Used for treatment-resistant schizophrenia and to reduce suicidal behavior in schizophrenia and schizoaffective disorder.

– Effective for treatment-resistant cases where other antipsychotics fail.
– Lower risk of extrapyramidal side effects compared to typical antipsychotics.
– Reduces suicidal tendencies in schizophrenia patients.

– Risk of agranulocytosis (severe drop in white blood cells requiring regular monitoring).
– Weight gain and metabolic issues (diabetes, increased cholesterol).
– Sedation and excessive drooling.
– Risk of seizures at higher doses.

Figure 3: A phenyl-piperidinyl-butyrophenone that is used primarily to treat schizophrenia and other psychoses . It is also used in schizoaffective disorder, delusional disorders, ballism, and tourette syndrome (a drug of choice) and occasionally as adjunctive therapy in intellectual disability and the chorea of huntington’s disease. It is a potent antiemetic and is used in the treatment of intractable hiccups. (From AMA Drug Evaluations Annual, 1994, p279)

Figure 4: A tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.

Genetic Insights and Future Directions

Recent genetic studies have identified several schizophrenia risk genes involved in Wnt signaling. For example, DISC1, a gene linked to brain development, directly interacts with Wnt signaling proteins, influencing neuronal function.[4] Additionally, AKT1, another schizophrenia risk gene, modulates GSK3 activity, further tying together genetic predisposition and molecular pathways in the disorder.[5]

Understanding these connections could pave the way for new treatment options that go beyond traditional dopamine-targeting antipsychotics. Novel drugs designed to fine-tune Wnt signaling could offer more precise and effective treatments with fewer side effects.[6]

Why This Matters

The public should be aware of these developments because they impact how we approach mental health treatment. By staying informed, we can support scientific research, advocate for improved therapies, and reduce the stigma surrounding psychiatric disorders. Additionally, recognizing that mental illnesses have a biological basis reinforces the importance of medical treatment and continued innovation in drug development.

As research into Wnt and GSK3 signaling progresses, we may witness the advent of next-generation antipsychotics that are more effective, personalized, and capable of addressing the underlying causes of psychiatric disorders rather than just their symptoms. This is an exciting time in neuroscience, and the more we understand, the better we can support those affected by schizophrenia and related conditions.

References:

Singh KK. “An emerging role for Wnt and GSK3 signaling pathways in schizophrenia.” Clinical Genetics, 2013. DOI: 10.1111/cge.12111
Clevers H, Nusse R. “Wnt/β-catenin signaling and disease.” Cell, 2012. DOI: 10.1016/j.cell.2012.05.012
Beaulieu JM, Gainetdinov RR, Caron MG. “Akt/GSK3 signaling in the action of psychotropic drugs.” Annual Review of Pharmacology and Toxicology, 2009. DOI: 10.1146/annurev.pharmtox.011009.081849
Mao Y, Ge X, Frank CL et al. “Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3β/β-catenin signaling.” Cell, 2009. DOI: 10.1016/j.cell.2009.03.033
Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA. “Convergent evidence for impaired AKT1-GSK3β signaling in schizophrenia.” Nature Genetics, 2004. DOI: 10.1038/ng1296
Ripke S, Sanders AR, Kendler KS et al. “Genome-wide association study identifies five new schizophrenia loci.” Nature Genetics, 2011. DOI: 10.1038/ng.940

Uncategorized

Unlocking Schizophrenia’s Mysteries: The Role of Wit and GSK3 Signaling Pathways

Posted on March 26, 2025 by ealslebe / 0 Comment

Schizophrenia is a complex, debilitating psychiatric disorder that affects millions worldwide. It manifests through hallucinations, delusions, cognitive impairments, and social withdrawal, significantly diminishing quality of life. Despite extensive research, the biological roots of schizophrenia remain elusive, limiting treatment options to managing symptoms rather than addressing underlying causes. Recent advances, however, highlights the importance of Wnt signaling and Glycogen Synthase Kinase 3 (GSK3) pathways, providing new insights that could revolutionize our understanding of schizophrenia and open doors for novel treatments. [1]

Why Should You Care About Wnt and GSK3?

Schizophrenia’s global burden is immense, ranking among the top causes of disability. Treatments currently available – primarily antipsychotics – focus on alleviating positive symptoms like hallucinations but fail to tackle cognitive deficits and the disease’s biological roots. Exploring Wnt and GSK3 pathways not only deepens our understanding of schizophrenia but may also pave the way for targeted therapies that improve long-term outcomes. [1]

Beyond schizophrenia, these signaling pathways are implicated in other conditions like bipolar disorder, autism, and neurodegenerative diseases. Advances in this research may have far-reaching implications for mental health and brain development disorders as a whole. [1]

What’s the Wnt/GSK3 Pathway, and How Does it Connect to Schizophrenia?

Think of Wnt as the brain’s construction supervisor. It helps build the brain during development and keeps neurons communicating properly throughout life. When Wet signaling works, it keeps things in balance by regulating a protein called β-catenin, which helps turn on genes critical for healthy brain function. [1]

Here’s where GSK3 comes in. When Wnt is off, GSK3 tags β-catenin for destruction. But when Wnt is on, it blocks GSK3, saving β-catenin and allowing important genes to do their job (see figure 1).

Figure 1: Wnt signaling pathways—showing how GSK3 controls β-catenin levels [2]

In people with schizophrenia, scientists suspect that Wnt signaling is disrupted. That disruption might affect how the brain develops and connects, contributing to symptoms like memory issues and impaired thinking. [1]

Medications Already Target Wnt and GSK3 – Without Us Realizing It

Here’s the kicker: many common psychiatric drugs may already work by influencing this pathway – we just didn’t know it until recently.

For Example (refer to figure 2):

Antipsychotics like clozapine and haloperidol not only block dopamine (the usual target) but also alter GSK3 activity, changing β-catenin levels. [3]
Lithium, a go-to treatment for bipolar disorder, directly inhibits GSK3 and boosts Wnt signaling, which might explain its mood-stabilizing effects. [1]
Newer drugs targeting glutamate receptors (mGlu3/3) also seem to activate Wnt pathways, offering fresh hope for better treatments. [4]

Figure 2: How antipsychotics, lithium, and glutamate drugs influence Wnt/GSK3 pathways [5]

The Genetic Connection: Are Some People Born with Wnt Pathway Risks?

Recent genetic studies show that some schizophrenia risk genes directly affect Wnt signaling:

DISC1 was first discovered in a Scottish family with a history of schizophrenia. DISC1 interacts with GSK3, regulating β-catenin and impacting brain development.
AKT1, another gene involved in blocking GSK3, is often found at low levels in schizophrenia patients. [6]
Researchers have also found mutations and copy number variations (CNVs) in Wnt-related genes like BCL9, which can alter brain size and connectivity.

This genetic evidence strengthens the case that Wnt signaling isn’t just involved – but may be central to how schizophrenia develops. [1]

Animal Studies Back it Up

Mice engineered to have defects in Wnt signaling – like knocking out the Dvl1 gene – show schizophrenia-like behaviors, such as social withdrawal and memory problems. Other mouse models confirm that too much or too little GSK3 activity can trigger hyperactivity, cognitive issues, and mood swings – mirroring what we see inhuman patients. [7]

Where Do We Go From Here?

Research into Wnt and GSK3 is giving scientists a whole new roadmap to understanding schizophrenia. Instead of just treating the symptoms, future therapies might target these pathways to protect the brain, improve cognition, and possibly even prevent the illness from progressing.

And because Wnt and GSK3 are involved in so many brain functions, this research could also unlock treatments for conditions like autism, bipolar disorder, and dementia. The more we understand these pathways, the closer we get to helping those living with these conditions.

References

[1] Singh, K. (2013). An emerging role for Wnt and gsk3 signaling pathways in schizophrenia. Clinical Genetics, 83(6), 511–517. https://doi.org/10.1111/cge.12111

[2] McCubrey, J. A., Steelman, L. S., Bertrand, F. E., Davis, N. M., Abrams, S. L., Montalto, G., D’Assoro, A. B., Libra, M., Nicoletti, F., Maestro, R., Basecke, J., Cocco, L., Cervello, M., & Martelli, A. M. (2013, June 19). Multifaceted roles of GSK-3 and Wnt/β-catenin in hematopoiesis and leukemogenesis: Opportunities for Therapeutic Intervention. Nature News. https://www.nature.com/articles/leu2013184

[3] Freyberg, Z., Ferrando, S. J., & Javitch, J. A. (2010). Roles of the AKT/GSK-3 and Wnt signaling pathways in schizophrenia and antipsychotic drug action. American Journal of Psychiatry, 167(4), 388–396. https://doi.org/10.1176/appi.ajp.2009.08121873

[4] Dogra, S., Stansley, B. J., Xiang, Z., Qian, W., Gogliotti, R. G., Nicoletti, F., Lindsley, C. W., Niswender, C. M., Joffe, M. E., & Conn, P. J. (2021). Activating mglu3 metabotropic glutamate receptors rescues schizophrenia-like cognitive deficits through metaplastic adaptations within the Hippocampus. Biological Psychiatry, 90(6), 385–398. https://doi.org/10.1016/j.biopsych.2021.02.970

[5] Vallée, A., Vallée, J.-N., & Lecarpentier, Y. (2021, April 26). Lithium and atypical antipsychotics: The possible Wnt/? pathway target in glaucoma. MDPI. https://www.mdpi.com/2227-9059/9/5/473

[6] Thiselton, D. L., Maher, B. S., Webb, B. T., Bigdeli, T. B., O’Neill, F. A., Walsh, D., Kendler, K. S., & Riley, B. P. (2009). Association analysis of the pip4k2a gene on chromosome 10p12 and schizophrenia in the Irish study of high density schizophrenia families (ISHDSF) and the Irish case–Control Study of schizophrenia (ICCSS). American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 153B(1), 323–331. https://doi.org/10.1002/ajmg.b.30982

[7] Powell, C. M., & Miyakawa, T. (2006). Schizophrenia-relevant behavioral testing in rodent models: A uniquely human disorder? Biological Psychiatry, 59(12), 1198–1207. https://doi.org/10.1016/j.biopsych.2006.05.008

Uncategorized

Wnt and GSK3 Signaling: The Overlooked Keys to Schizophrenia?

Posted on March 26, 2025 by adebleye / 0 Comment

Schizophrenia has long been one of psychiatry’s most puzzling disorders. We’ve treated its symptoms for decades with antipsychotics that blunt hallucinations but fail to address the root cause. But what if the real story begins not with neurotransmitters, but with developmental pathways that shape the brain itself? Emerging research suggests that two cellular signaling systems—Wnt and GSK3—might hold critical answers.

Schizophrenia as a Neurodevelopmental Disorder

The old view of schizophrenia as simply a “chemical imbalance” is giving way to a more nuanced understanding: this may fundamentally be a disorder of brain development. Epidemiological studies show that prenatal infections, birth complications, and early cognitive delays all increase schizophrenia risk. Brain imaging reveals subtle structural differences in neural connectivity. Together, this paints a picture of a brain wired differently from the start.

This shift in perspective matters because it changes where we look for solutions. If schizophrenia stems from developmental miscues, then the pathways guiding brain construction—like Wnt signaling—become prime suspects.

Wnt Signaling: The Brain’s Blueprint

The Wnt pathway is a cornerstone of embryonic development, governing everything from stem cell proliferation to synapse formation. It operates through three main branches:

The Canonical (β-Catenin) Pathway – Regulates gene expression critical for neuronal survival and growth.
Planar Cell Polarity (PCP) Pathway – Directs the migration and positioning of neurons.
Wnt/Calcium Pathway – Fine-tunes synaptic communication.

When Wnt signaling falters, the brain’s architecture can veer off course. And intriguingly, several schizophrenia-linked genes, like DISC1 and Akt1, intersect directly with this pathway.

GSK3: The Lithium Connection

Glycogen synthase kinase 3 (GSK3) acts as a key regulator of Wnt signaling by controlling the stability of β-catenin. Normally, GSK3 keeps β-catenin in check, ensuring cells don’t overgrow. But when GSK3 is overactive, it can disrupt neural development and function.

Here’s where things get fascinating: lithium, one of psychiatry’s oldest drugs, works by inhibiting GSK3. This not only stabilizes mood in bipolar disorder but also suggests that GSK3 dysregulation might play a role in schizophrenia. Some antipsychotics, like haloperidol, appear to indirectly modulate this same pathway, hinting that their therapeutic effects might partly stem from Wnt/GSK3 interactions.

Genetic Clues Pointing to Wnt and GSK3

Several schizophrenia risk genes converge on these pathways:

DISC1 – Mutations in this gene disrupt GSK3 regulation, leading to abnormal Wnt signaling. Remarkably, lithium’s effects mimic what happens when DISC1 functions properly.
Akt1 – Reduced Akt1 activity, common in schizophrenia patients, fails to rein in GSK3, leaving β-catenin unstable.
BCL9 – Found within a schizophrenia-linked chromosomal deletion, this gene helps β-catenin regulate brain size. Errors here could alter early brain development.

Animal Models Reinforce the Link

Mouse studies further support this connection. Animals with disruptions in Wnt-related genes (like Dvl1 knockouts) exhibit behaviors resembling schizophrenia, including social deficits and sensory processing abnormalities. Conversely, boosting β-catenin produces effects similar to lithium treatment—calmer, more resilient behavior. These findings suggest that tweaking Wnt/GSK3 signaling could one day yield more precise treatments.

Why This Matters for the Future

Better Treatments – Current antipsychotics are crude tools, often causing debilitating side effects. Targeting Wnt/GSK3 could lead to therapies that correct underlying developmental errors rather than just masking symptoms.
Early Intervention – If we can identify at-risk individuals through genetic or biomarker screening, we might intervene before psychosis ever emerges.
Broader Implications – Since Wnt and GSK3 are also implicated in autism, bipolar disorder, and Alzheimer’s, understanding their role in schizophrenia could shed light on multiple conditions.

The Road Ahead

The next steps are clear but challenging:

Develop safer, more specific GSK3 inhibitors to replace lithium’s blunt approach.
Use stem cell models to study how Wnt signaling goes awry in schizophrenia patients.
Explore whether early-life interventions—perhaps even prenatal treatments—could prevent the disorder altogether.

Final Thoughts

Schizophrenia has resisted simple explanations for too long. But by shifting focus to the pathways that build the brain—Wnt and GSK3—we might finally be closing in on its origins. This isn’t just about biochemistry; it’s about how the brain assembles itself, and how slight missteps in that process can have lifelong consequences.

For anyone affected by schizophrenia, or anyone who cares about mental health research, this is a story worth following. Because if we’re right about Wnt and GSK3, we’re not just treating a disorder—we’re rewriting how we understand it.

Uncategorized

Wnt and GSK3 Signaling: The Overlooked Keys to Schizophrenia?

Posted on March 26, 2025 by adebleye / 0 Comment

Uncategorized

Mental Illness

Posted on March 26, 2025 by rhurley1 / 0 Comment

The article we have covered in a previous week, “An emerging role for Wnt and GSK3 signaling pathways in schizophrenia” by Jacques L. Michaud was an article about the basics on schizophrenia disorder and how it may be connected to Wnt (pronounced “went”) and GSK3 pathways. Basically, it works as following; we commonly think of schizophrenia as a disorder in perception and many other domains throughout common society. However, the article points out a fascinating new and notable consistent pattern where Wnt and GSK are decreased and increased in the body respectively within a case of schizophrenia.^1 The topic today is why people should care about this topic and what the people must know, so without further ado let’s get reading!

The article informs us that some of the distinguishable characteristics of schizophrenia disorder are connected to Wnt and GSK. Though, the article specifically focuses mainly on how poking at these two pathways are done to treat schizophrenia. As a result of this connection, we can now classify an immeasurably correlation here.

Figure two from the article mentioned above is especially excellent at explaining this where it was needed (excellently timed, or in other words placed well). That piece is simultaneously even a diagram which shows even a seemingly full diagram of the Wnt pathway used in pharmaceutical intervention. Although, one slight problem could be that it could feel a tad bit overwhelming if you’re not too familiar with the applied terms of figure two in the Neuroscience field. This was an excellent piece to me for it is maximized simplicity because, for clear reasons, that kind of thing strongly helps. The figure may also benefit people uninvolved in Neuroscience as well because figure two works similarly like speech bubbles in comic books with all the brief, yet descriptive, labeling, and I find that effective myself in general because it’s easy on the eyes to track or logicate.

Now, at this point, one, such as yourself, may wonder why people really should care about all the above information. Well, let’s answer with essential basics to answer ourselves by quickly asking ourselves something simpler first; what really is schizophrenia disorder? Well, schizophrenia is not the nicest experience one can have. According to Mayo Clinic, schizophrenia is known to be a, “serious mental health condition that affects how people think, feel and behave”^2 that in some cases can turn into medical emergencies (suicide attempts, concernable behavior, or inaccessiblities to core needs. Considering that we know that our core senses to be most essential, it’s no shock to pretty much anyone that such a scenario can turn serious fast. Let us put this into perspective with some real world folks.

Lionel Aldridge, for example, experienced symptoms along the lines of paranoia, irritation, social struggles. In life, he was a sport athlete with a winner of 3 world sports championships and many NFL games throughout his career as defense. He experienced a myriad of challenges partly due to schizophrenia such as his journey to recovery from the disease (which was a success), homelessness where he lost a superbowl ring during, etc.

Sources:
1: An emerging role for Wnt and GSK3 signaling pathways in schizophrenia” by Jacques L. Michaud
2: https://www.mayoclinic.org/diseases-conditions/schizophrenia/symptoms-causes/syc-20354443

Health/Uncategorized

From Wnt to Wonder; The Neuroscience Behind Schizophrenia

Posted on March 26, 2025 by jcopiske / 0 Comment

From Wnt to Wonder → The Neuroscience Behind Schizophrenia

Schizophrenia is a complex and misunderstood disorder that affects emotional and physical behavior. Even though this disorder affects millions, it remains a poorly understood developmental disorder. The stigma that co-occurs with Schizophrenia leads to oversimplified symptomology.

However, emerging research reveals Schizophrenia is strongly linked to the Wnt pathway, which is a network of proteins that work together in brain developement, communications, and homeostasis. Research suggests that dysregulation of the Wnt pathway could be the root of Schizophrenia, leading to the importance of understanding what Schizophrenia is and how it manifests.

What is Schizophrenia?

This disorder is multifaceted; affecting thought processes, emotions, and behaviors. There are many misunderstandings and stigmas surrounding Schizophrenia. Characteristics in symptomology lead to discrimmination which overshadows the biological and developmental beginnings of the disorder.

There are five different subtypes of Schizophrenia. The symptoms for each subtype vary, and understanding these subtypes could be helpful in recognizing the symptomology and how it connects to the biology beneath the surface.

Paranoid: Most common form: consists of hallucinations and/or delusions, speech and emotions may not be affected, develops later in life.

Disorganized/Hebephrenic: Develops 15-25 years, disorganized behavior, and thoughts, short lasting hallucinations/delusions, may have diagnosed speech patterns and others may find it difficult to understand you.

Catatonic: Move from being very active to very still, may not talk much, can mimic others speech and movement.

4. Undifferentiated– some signs of each

5. Residual -history of psychosis, only negative symptoms, slow movement, poor memory, lack of concentration, and poor hygiene

What is the Wnt Pathway?

One pathway has emerged as a critical path in Schizophrenia: the Wnt pathway. This is a network of proteins that communicate signals through cellular processes and facilitate regulation and communication throughout the brain. Methods have uncovered that dysregulation of the Wnt pathway is linked to multiple developmental disorders, contributing to cognitive deficits, structural brain changes, and symptomology. Structural brain changes cause alterations in neural connectivity that contribute to cognitive deficits and emotional dysregulation.

The Wnt pathway is used in a range of biological processes such as cell development, homeostasis, and differentiation which is why the pathway is so critical in psychiatric disorders. All processes stimulate each other, the Wnt pathway can be evalutated to understand why symptoms occur in Schizophrenia and ways to prevent them.

Think of the Wnt pathway as a series of relay runners passing a baton (signals) to regulate brain processes. When something disrupts the relay, its like dropping the baton- leading to the changes, neurological and behavioral, that we see associated with Schizophrenia.

The Science of the Wnt Pathway

The Wnt pathway is essentially a network of Wnt proteins, which are a family of secreted glycoproteins that bind to receptors on the surface of cells which in turn initiates a cascade of signaling events. Frizzled (Fz) receptors are the primary receptors for Wnt proteins. When Wnt binds to Fz receptors, intracellular signaling cascades are activated and trigger various cellular responses. Two pathways that can be trigged are a canonical pathway and a noncanonical pathway. Beta catenin is involved when a canonical pathway is trigged by an intracellular signaling cascade. On the other hand, when a noncanonical pathway is triggered, beta catenin is not involved in the process.

Fig. 2 Causation for psychotic symptoms; processes stimulate one another

How it works: Beta Catenin

β-Catenin is a central component of the canonical Wnt signaling pathway, which regulates a wide variety of cellular processes such as cell differentiation, proliferation, migration, and synaptic plasticity. It acts as a transcriptional co-activator that, in the presence of Wnt signaling, translocates to the nucleus and binds to T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors to initiate gene expression.

Altered β-catenin signaling during critical periods of brain development, especially in the formation and maintenance of neural circuits, may contribute to cognitive deficits and impaired synaptic plasticity seen in Schizophrenia. β-Catenin’s role in regulating synaptic function might be disrupted in individuals with Schizophrenia, affecting neuronal connectivity and circuit formation.

Two Important Pathways

The Wnt pathway is critical for optimal brain health. By understanding the relationship between the Wnt pathway and Schizophrenia we can see a potential future of treatment possibilities. Research proposes that interventions of the Wnt pathway could improve life quality for those with Schizophrenia.

Fig 3. When the Wnt pathway is in charge of self renewal, differentiation, microenvironment, quiescence, senescence, and cancer stem cells

Canonical

The canonical pathway produces beta catenin. This pathway is initiated when Wnt ligands bind to receptors on the cell membrane, primarily a Fz family receptor with low-density lipoprotein receptor-related proteins. The pairing of these two molecules sets off a chain reaction inside the cell.

Without Wnt signaling (when it’s turned off), beta catenin is broken down by the destruction complex, which is a group of proteins involving, GSK3β, Axin, APC, and CK1α. This group of proteins stays assembled when Wnt signaling is off. If Wnt ligands are binding to their receptors (Wnt signaling is on) the complex is disassembled. Therefore, beta catenin is accumulated in the cytoplasm and moves to the cell nucleus. Beta catenin then has the ability to interact with co-factors like TCF/LEF to initiate the transcription of Wnt-dependent target genes.

Fig. 4 Comparison of Wnt signaling off/on

Noncanonical

Does not involve β-catenin-mediated transcription
Two pathways are the planar cell polarity (PCP) and Wnt/calcium pathways
- PCP signaling involves Wnt signaling through Fz receptors and G proteins
  - Rho and Rac proteins are activated to regulate the cytoskeleton
The Wnt/calcium pathway is triggered by Fz activation
- Increases intracellular Ca2+ levels
  - Leads to the activation of protein kinase C (PKC), affecting a broad range of cellular functions
    - Particularly in the central nervous system (CNS) which influences neural circuit formation and synaptic plasticity

What’s the big whoop?

Schizophrenia is a complex psychiatric disorder with significant neurodevelopmental and genetic groundwork. By understanding the inner-workings of Wnt signaling, research can open new innovative therapies that potentially could change the lives of individuals with Schizophrenia.

Recent research has highlighted the critical role of the Wnt signaling pathway, particularly β-catenin, in the development and progression of Schizophrenia. β-Catenin is a key player in the canonical Wnt pathway.

β-Catenin and the Wnt signaling pathway play a significant role in brain development, synaptic function, and cognitive processes. Dysregulation of this pathway, particularly through altered β-catenin signaling, is emerging as an important factor in the development of Schizophrenia. As research continues, understanding the precise role of β-catenin could open new doors for targeted therapies, offering hope for better treatment strategies for this complex and debilitating disorder.

By exploring the intersection of genetic, molecular, and pharmacological factors in Wnt signaling, we move closer to understanding the biological basis of Schizophrenia and developing more effective treatments.

References

KK;, S. (n.d.). An emerging role for Wnt and GSK3 signaling pathways in Schizophrenia. Clinical genetics. https://pubmed.ncbi.nlm.nih.gov/23379509/

Liu, J., Xiao, Q., Xiao, J., Niu, C., Li, Y., Zhang, X., Zhou, Z., Shu, G., & Yin, G. (2022, January 3). Wnt/β-catenin signalling: Function, biological mechanisms, and therapeutic opportunities. Nature News. https://www.nature.com/articles/s41392-021-00762-6

MacDonald, B. T., Tamai, K., & He, X. (2009). Wnt/beta-catenin signaling: components, mechanisms, and diseases. Developmental cell, 17(1), 9–26. https://doi.org/10.1016/j.devcel.2009.06.016

Uncategorized

Brain Traffic Control: How Akt Keeps Your Neural Highways Running Smoothly

Posted on March 26, 2025 by Nessa Angau / 0 Comment

Traffic Management & Traffic Control Solutions | Digi International

Imagine your brain as a bustling city. Neurons are the citizens, busily transmitting signals and information. To keep the city running smoothly, there’s a complex network of roads and traffic lights—this is your Wnt signaling pathway. Now, meet Akt, the traffic controller who makes sure everything flows without chaos.

What is Akt, and Why Should You Care?

Akt, short for protein kinase B (PKB), is like a supervisor in your brain. It manages cell growth, survival, and even how cells talk to one another. But one of its most fascinating jobs is regulating the Wnt signaling pathway, which controls how neurons grow and connect. When the system works well, it’s like green lights at every intersection. When it doesn’t, things get jammed up—and that can contribute to brain disorders like schizophrenia.

How Akt and Wnt Work Together

According to research on in the canonical Wnt pathway in schizophrenia (the main road in our city analogy), a protein called GSK3β is like a demolition crew. It breaks down a protein named β-catenin, which is essential for turning on brain-friendly genes [1]. But here’s where Akt steps in: it hits the brakes on GSK3β, preventing it from destroying too much β-catenin. This means those beneficial genes can activate, supporting brain development and maintenance.

Lithium, a medication often used to treat mood disorders, also stops GSK3β. But research suggests lithium works best when Akt is already on the job. Without Akt’s help, lithium’s effect would be like a malfunctioning traffic light—not as effective [2].

When Things Go Wrong

The possible role of the Akt signaling pathway in schizophrenia - ScienceDirect — Figure 1. The signaling pathway of Akt in schizophrenia [1]

In schizophrenia, Akt sometimes goes offline, leaving GSK3β unchecked (Singh, 2013). This means less β-catenin reaches its destination, leading to problems in brain connectivity and communication. Think of it like broken traffic signals causing congestion and confusion.

This disruption doesn’t just impact thinking and memory; it also affects emotional regulation and perception. Low Akt activity may contribute to the hallucinations, delusions, and cognitive deficits that characterize schizophrenia. Research has also shown reduced Akt1 expression in the brains of people with schizophrenia, further underscoring its importance [3].

Moreover, genetic mutations or variations that reduce Akt’s effectiveness can make individuals more susceptible to developing schizophrenia. In some cases, environmental factors like stress or substance abuse can further impair Akt signaling.

Fortunately, some antipsychotic medications give Akt a boost. By restoring its activity, they help get Wnt signaling back on track, reducing symptoms and improving cognitive function. Lithium, for example, indirectly enhances Akt function by inhibiting GSK3β, providing a double layer of protection against disrupted Wnt signaling.

Emerging research is also exploring the use of Akt activators or other drugs that directly target this pathway. These new approaches could offer more effective treatment options with fewer side effects in the future.

The Potential of Akt-Targeted Therapies

Targeting PI3K/Akt signal transduction for cancer therapy | Signal Transduction and Targeted Therapy.https://media.springernature.com/lw685/springer-static/image/art%3A10.1038%2Fs41392-021-00828-5/MediaObjects/41392_2021_828_Fig3_HTML.png — Figure 2. Diagram showing targeting on PI3K/AKT Pathway for cancer therapy [4]

While Akt’s role in schizophrenia is well-studied, its influence extends to other neurological and psychiatric disorders. Dysregulation of the Akt pathway has been linked to bipolar disorder, depression, and even Alzheimer’s disease. Researchers are investigating how therapies that target Akt could help manage these conditions by restoring proper signaling pathways.

Studying Akt in animal models and human stem cell systems is also helping scientists understand how it influences brain function. Advanced imaging and molecular techniques are providing new insights into how Akt and Wnt signaling networks operate in real-time. This research is essential for developing better interventions for brain health.

Final Thoughts

AKT FORMATION | Road Signaller Services | 450 661-6470

Akt may not be a household name, but its influence in your brain is undeniable. From preventing neurological roadblocks to ensuring essential signals get through, it’s the ultimate traffic controller of your mental metropolis. Understanding and supporting Akt’s function could open doors to better treatments for brain disorders in the future.

Moreover, lifestyle factors like regular exercise, a balanced diet, and stress management may support healthy Akt function. Maintaining overall brain health can be a proactive way to ensure this critical signaling pathway remains balanced.

As science advances, personalized medicine approaches are expected to further refine Akt-targeted therapies. By tailoring treatments to individual genetic and biochemical profiles, healthcare providers may achieve more effective and lasting outcomes.

Next time you hear about brain health, remember to thank Akt—your brain’s reliable traffic marshal!

Resources:

[1] Singh, K. (2013). An emerging role for Wnt and GSK3 signaling pathways in schizophrenia. Clinical Genetics, 83(6), 511–517. https://doi.org/10.1111/cge.12111

[2] Chokhawala, K., Saadabadi, A., & Lee, S. (2024, January 14). Lithium. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK519062/

[3] Chang, C.-Y., Chen, Y.-W., Wang, T.-W., & Lai, W.-S. (2016). Akting up in the GABA hypothesis of schizophrenia: Akt1 deficiency modulates GABAergic functions and hippocampus-dependent functions. Scientific Reports, 6(1). https://doi.org/10.1038/srep33095

[4] He, Y., Sun, M. M., Zhang, G. G., Yang, J., Chen, K. S., Xu, W. W., & Li, B. (2021). Targeting PI3K/Akt signal transduction for cancer therapy. Signal Transduction and Targeted Therapy, 6(1), 1–17. https://doi.org/10.1038/s41392-021-00828-5

Health

The Brain’s Hidden Modulator: How Cannabinoid Receptors Shape Neurological Health

Posted on March 25, 2025 by smohame4 / 0 Comment

Why Cannabinoid Receptors in the Brain Matter More Than You Think

The brain is an intricate network of neurons and chemical signals, constantly adapting and responding to the world around us. But did you know that the brain has its own cannabis-like system? Scientists have discovered that the endocannabinoid system (ECS) plays a crucial role in regulating mood, memory, pain, and even neuroprotection. However, despite its importance, many people remain unaware of how this system functions and its potential impact on human health.

Our understanding of the ECS has grown tremendously, and researchers now recognize that its dysfunction is linked to various neurological conditions. Scientists have found that cannabinoid receptors, particularly CB1 and CB2, are essential in modulating brain activity and protecting against neurodegeneration. But there’s still much to learn, and unlocking the full potential of this system could revolutionize medicine.

Therefore, by studying cannabinoid receptors, we may uncover groundbreaking treatments for conditions such as Alzheimer’s, multiple sclerosis, and traumatic brain injuries. The future of neuroscience and medicine may lie in harnessing the power of cannabinoids, making this an area of research that deserves our attention.

The Science Behind Cannabinoid Receptors

The article “Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease” explores how CB1 and CB2 receptors influence brain function and disease[1]. CB1 receptors are abundant in the brain, particularly in regions associated with cognition, movement, and emotion, such as the hippocampus, neocortex, and basal ganglia. They regulate neurotransmitter release, affecting everything from anxiety to learning ability. Meanwhile, CB2 receptors, though primarily found in immune cells, have been discovered in the brain as well, where they play a role in inflammation and neuroprotection[2].

Figure 1. This figure highlights the pathways activated by cannabinoid receptors, showing how they modulate synaptic plasticity and neuronal signaling[3].

What Are CB1 Agonists?

CB1 agonists are substances that mimic the action of endocannabinoids, such as anandamide and 2-arachidonoylglycerol (2-AG), by binding to CB1 receptors and triggering a biological response. These agonists can be natural, like tetrahydrocannabinol (THC) from cannabis, or synthetic, such as certain pharmaceutical drugs designed to target the ECS.

Mechanism of Action

CB1 receptors are G-protein-coupled receptors (GPCRs), which means they influence intracellular signaling pathways when activated. When a CB1 agonist binds to the receptor, it triggers a cascade of biochemical reactions:

Inhibition of Adenylyl Cyclase – This reduces cyclic AMP (cAMP) levels, leading to decreased activation of protein kinase A (PKA), which ultimately affects neurotransmitter release.
Modulation of Ion Channels – CB1 activation leads to the inhibition of voltage-gated calcium channels and activation of potassium channels, reducing neuronal excitability and neurotransmitter release.
Neurotransmitter Regulation – By inhibiting the release of neurotransmitters like glutamate, dopamine, and GABA, CB1 agonists can influence mood, pain perception, and cognitive function.

Effects of CB1 Agonists

The physiological and psychological effects of CB1 agonists depend on the dosage and specific compound used. Some of the key effects include:

Euphoria and Relaxation – Common with THC, which activates CB1 receptors in the brain’s reward pathways.
Pain Relief – By modulating pain signaling in the central nervous system.
Appetite Stimulation – Often referred to as the “munchies,” this effect is commonly observed with THC.
Cognitive and Motor Impairment – Excessive CB1 activation can impair memory and coordination.
Anxiolytic or Anxiogenic Effects – Depending on the individual and dose, CB1 agonists may reduce or increase anxiety.

Current Applications of CB1 Agonists

CB1 agonists have shown promise in treating several conditions. Click here to learn more about their use.

Pain Management: Synthetic CB1 agonists such as dronabinol and nabilone are used to alleviate chronic pain in cancer and neuropathic disorders[4].
Appetite Stimulation: These compounds have been prescribed to counteract weight loss in patients undergoing chemotherapy or suffering from HIV/AIDS[5].
Neuroprotection: Research suggests that CB1 activation can protect against neurodegenerative diseases such as Alzheimer’s and Parkinson’s by reducing excitotoxicity and inflammation[6].
Mental Health: While THC can induce psychoactive effects, regulated CB1 agonists may have potential in treating anxiety and PTSD[7].

Risks and Considerations

While CB1 agonists offer potential therapeutic benefits, excessive or prolonged activation of CB1 receptors can lead to:

Cognitive Impairment
Dependency and Tolerance
Increased Risk of Psychosis in Susceptible Individuals
Cardiovascular Effects, Such as Increased Heart Rate

Figure 2 . This figure shows the interaction of CB1 agonsit with receptor to enhance pain management.

A Future of Possibilities

Despite its immense potential, cannabinoid research faces hurdles, particularly due to legal and regulatory challenges surrounding cannabis. While THC—the psychoactive component of marijuana—activates CB1 receptors, leading to its well-known effects, research is focusing on developing therapies that harness the benefits of the ECS without unwanted side effects.

Understanding cannabinoid receptors isn’t just about cannabis—it’s about unlocking new treatments for some of the most challenging neurological diseases. As research progresses, the potential for cannabinoid-based medicine continues to grow. The more we explore this system, the closer we get to innovative therapies that could transform lives.

So, the next time you hear about cannabinoids, remember—they’re not just about recreational use. They’re part of a sophisticated system that could hold the key to better brain health.

Footnotes

[1] Abrams, D. I., et al. (2003). Cannabis in painful HIV-associated sensory neuropathy. Neurology.

[2] Aso, E., & Ferrer, I. (2014). Cannabinoids for treatment of Alzheimer’s disease: Moving toward the clinic. Frontiers in Pharmacology.

[3] Blessing, E. M., et al. (2015). Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics.

[4]Kendall, D. A., & Yudowski, G. A. (2017). Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease. Frontiers in Cellular Neuroscience.

[5] Laprairie, R. B., et al. (2016). Biased CB1 cannabinoid receptor signaling in Huntington’s Disease. Molecular Pharmacology.

[6] Mechoulam, R., & Parker, L. A. (2013). The endocannabinoid system and the brain. Annual Review of Psychology.

[7] Mechoulam, R., & Shohami, E. (2007). Endocannabinoids and traumatic brain injury. Molecular Neurobiology.

[8] Otero-Romero, S., et al. (2016). The role of cannabinoids in multiple sclerosis treatment. Multiple Sclerosis Journal.

[9] Pertwee, R. G. (2010). Targeting the endocannabinoid system with cannabinoid receptor agonists. Philosophical Transactions of the Royal Society B.

Health/Hot topics

Unlocking the Mind: How Wnt Pathways Shape Brain Development and Schizophrenia Risk

Posted on March 25, 2025 by smohame4 / 0 Comment

Schizophrenia is a complicated brain health condition that affects millions of people worldwide. But even though we know a lot about it, we still don’t fully understand what causes it. That being said, recent research has zeroed in on the Wnt signaling pathway and its connection to Glycogen Synthase Kinase 3 (GSK3) as key players in brain development and schizophrenia. Understanding how these pathways work doesn’t just help us understand the science behind schizophrenia, it also opens doors for new treatment options.

The Role of Wnt in Building a Healthy Brain

The Wnt signaling pathway is kind of like a traffic control system for brain development. It helps guide important processes like cell differentiation, neuron formation, and survival. There are two main branches:

The canonical pathway, which controls gene expression through β-catenin.
The non-canonical pathways, which regulate things like cell movement and calcium signaling.

Normally, when Wnt isn’t around, GSK3β tags β-catenin for destruction before it can activate any genes. But when Wnt binds to its receptors (Frizzled and LRP5/6), β-catenin is protected from being broken down. This allows it to reach the nucleus, where it turns on genes crucial for brain function.

Figure 1. This shows the wnt signaling pathway, specifically the canonical signalng where Wnt binds Frizzled (FZ) and LRP5/6, activating Disheveled (DVL) and inhibiting β-catenin degradation. Stabilized β-catenin enters the nucleus, activating gene expression.

How the Environment Affects Wnt and Schizophrenia

It’s not just genetics that shape brain health. Environmental factors can mess with Wnt signaling too, especially before birth. Things like prenatal infections, malnutrition, and toxin exposure can alter Wnt-related gene expression, which can rewire the brain in ways that increase schizophrenia risk.

For example, if a pregnant person gets an infection, their immune response can disrupt Wnt/GSK3 signaling in the developing brain, leading to changes similar to what we see in schizophrenia patients[1]. And it’s not just infections—pollutants like heavy metals and endocrine disruptors have been found to impact the epigenetic regulation of Wnt genes, which could contribute to the disorder later in life[2].

Figure. 2. this demostrates how schizophrenia arises from genetic factors (e.g., DRD2, DISC1, GRM3), epigenetic modifications, and environmental influences (e.g., stress, diet, substance use) affecting the gut, immune, and brain systems. Dysregulation of dopamine, serotonin, GABA, and glutamate contributes to symptoms.

Can We Lower the Risk of Schizophrenia?

While genetics play a role, research shows that lifestyle and environmental choices might help lower the risk. Some key strategies include:

Prenatal Care: Getting proper medical care during pregnancy, including vaccines and good nutrition, may help protect fetal brain development.
Reducing Toxin Exposure: Avoiding harmful chemicals like lead and pesticides could help keep Wnt signaling on track.
Dietary Support: Nutrients like omega-3s, folate, and vitamin D have been linked to healthy Wnt activity and brain growth[3].
Early Intervention: Spotting early signs of schizophrenia risk could lead to targeted treatments, like cognitive training or medications that support Wnt signaling[4].

Schizophrenia is still full of unknowns, but the more we learn about the Wnt and GSK3 pathways, the closer we get to better treatments and even prevention strategies. Understanding brain health on a molecular level is the first step toward changing the way we see and treat mental illness.

Footnotes

[1] Singh KK. An emerging role for Wnt and GSK3 signaling pathways in schizophrenia. Clin Genet. 2013; 83(6): 511-517.

[2] De Ferrari GV, Moon RT. The ups and downs of Wnt signaling in prevalent neurological disorders. Oncogene. 2006; 25(57): 7545–7553.

[3] Chenn A, Walsh CA. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science. 2002; 297(5580): 365–369.

[4] Gould TD, Einat H. β-catenin overexpression in the mouse brain phenocopies lithium-sensitive behaviors. Neuropsychopharmacology. 2007; 32(10): 2173–2183.