Cobbers on the Brain – Page 133 – Student Commentary on the Neurological Sciences

Autism Spectrum Disorder

Posted on April 26, 2016 by / 1 Comment

Autism spectrum disorder is commonly known for its social impairment, and the symptoms include abnormal social interaction and communication, and stereotyped behaviors with restricted interest. The neural mechanisms responsible for these behavioral symptoms have been intensively investigated by the scientific community in the last 30 years.
Researchers genetically modify rodents in order to better understand how Autism affects the brain. The genetic mutations produce a range of symptoms similar with the symptoms found in humans, but how the genetic mutations lead to behavioral symptoms of Autism is not fully understood.
Between the potential mechanisms underlying Autism are: neuroanatomical abnormalities, and excitatory and inhibitory imbalance. How these mechanisms are related, and how they give rise to autism is still being investigated.
Neuroanatomical abnormalities result from abnormalities in brain development, that can be caused by gene mutations, inappropriate levels of neurotrophines (a family of proteins that induce the survival, development, and function of neurons. They belong to a class of growth factors, secreted proteins that are capable of signaling particular cells to survive, differentiate, or grow), and environmental factors which, together or independently, are affecting brain development and leading to pathological states.
The brain can have excitatory and inhibitory synapses, that together, work in a balance that maintain our normal functioning, filtering main information and inhibiting “noisy” information. To maintain such balance, many proteins and neurotransmitters work together. In autism, the brain displays local over-connectivity and long range or inter-regional under-connectivity, both caused by excitatory and inhibitory imbalance. The imbalance is mainly caused by a flaw in one or more of the proteins responsible for maintaining the proper functioning of synapses. The defects in the proteins can be a result of gene mutations and environmental factors.
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The causes that lead to the onset of autism are still not fully understood, but with the scientific advancement, researchers are getting close to understand how the autistic brain is being affected by gene mutations and how we could target specific proteins in order to treat the disorder.

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What causes Autism?

Posted on April 26, 2016 by / 0 Comment

Autism had dramatically grown in the past fifty years. The US documented that 19 out of 10,000 individuals had autism in 1992. This rose to 1 in 150 in 2002, followed by 1 in 110 in 2006. As it can be seen, the growth in individuals with autism is huge. The reasons why this number has increased so greatly is not well known. One known contributor is the expansion of the autism spectrum, but there has to be more to it. Some people think vaccines are the cause, and others think genetics or even stress. So with the great confusion, my class decided to look deeper into autism and tried to define the true cause of it.
After reading and analyzing our paper for the week, some potential areas were targeted for a likely cause of autism.
As a whole, we discovered that very simplistically, neurally there is too much glutamate, excitatory neurotransmitters, and not enough GABA, inhibitory neurotransmitters, in the brain. This is causing a myriad of problems. Generically abnormal neuron migration and synchronization is occurring.
Looking deeper into the actual signaling pathway, there are numerous problems that could be occurring. One of which is too much protein synthesis, which produces more than necessary mRNA through over activity of FMRP and eIF4E. Another area of concern is the miscommunication between receptors NRX and NLGN, which cannot dimerize properly and is causing the imbalance of excitatory and inhibitory neurotransmitters. SynGAP also can be a part of potentially causing autism by not being shut down because it assists in the production of protein. In individuals with autism, they also see a decreased amount of Reelin and dysfunctions with Shank. The image of the pathways is located in the paper on top of page nine.
As you can see, there are various problems that can occur with autism and there is not one specific area that has been discovered to cause it.
I was specifically interested in environmental factors that could induce or cause autism. From what I found, there is not one environmental factor that causes autism, but rather, there are many different items that can induce autism in individuals with a genetic predisposition.
Some of the factors I found were diet, heavy metals, pesticides, stress during birth, drugs, and medications. Vaccines are a factor many individuals believe is the cause for autism. In many recent findings, each of them said that vaccines do not cause autism and it is much safer to vaccinate children from deadly illnesses than to have fear that they could get autism.
Again, there is not one distinct reason for the cause of autism, but tons of research is being done to see if it can be narrowed down to a specific area of the brain or an environmental factor in order to prevent autism growth in the future.

Community/Disease/Health

Why Are We Only Treating Half of Autism?

Posted on April 26, 2016 by / 0 Comment

In the United States today, approximately 1 in 68 children are diagnosed with Autism Spectrum Disorder (ASD). ASD is a disorder of the brain that can include, but is not limited to, social interaction difficulties, communication challenges, and a tendency to engage in repetitive behaviors. Autism is often misunderstood both in the public and in the scientific community. A large part of the problem is that it is not understood in the brain.

Autism diagnosed on a very large spectrum and people with the disorder vary on levels of functionality and ability to do things such as communicate, socialize, and control their behaviors. As for genetic factors, there are diverse variations underlying the development of ASD and this limits the development of medication for people living with ASD. Currently, there are only a few FDA-approved medications for ASD including a drug called Risperidone. Risperidone is a dopamine antagonist that acts as an antipsychotic in the brain and is most commonly used to treat schizophrenia and bipolar disorder. The problem with using this medication in ASD is that it doesn’t help with all the symptoms of the disorder. While taking the antipsychotic, there is a reduction in hyperactivity, irritability, and repetitive behaviors that people with ASD tend to experience. When these symptoms are treated, there still are the problems with social withdrawal and communication skills.

With this limited treatment option, the focus in research lies on cause of the social and communication impairments. Likely, the “core” of ASD symptoms can be attributed to problems in excitatory synapse transmission. As the brain was developing in ASD children, The greater the malfunction of excitatory pathways in the brain, the greater deficits. In excitatory pathways of ASD patients, studies have shown that there is improper development in adhesion molecules and scaffolding proteins. When these components are incorrectly developed, the excitatory pathways associated with social skills and communication are impacted negatively.

Unfortunately for ASD patients, the misunderstanding of this pathway malfunction is the reason they cannot be effectively treated. For this disorder, medication may or may not be the answer, but without understand the neuronal pathways affected, the scientific community can never find out. It is possible that behavioral therapy may be the most promising way to treat children with ASD. As research on autistic brains continues, hopefully the thousands of children with the disorder can benefit. Regardless of research outcomes, children with autism are full of light and deserve to be advocated for in any way possible. Advocacy needs to happen in the scientific, medical, and public settings for the 1 in 68 children currently living with ASD.
Fun fact: April is Autism Awareness Month!

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Oxytocin is More than Just a Love Hormone: Could it be the Future for ASD?

Posted on April 26, 2016 by / 0 Comment

It isn’t really possible to narrow autism down to one specific difference or symptom, really it is a combination of many different things. Every single case is unique, which is what makes it so difficult to treat.

In the 70s/80s it was estimated that 1 in every 2,000 kids had autism, the current numbers are 1 in every 150 8 year olds are diagnosed with an autism spectrum disorder (ASD). ASD would include subcategories such as Aspergers and pervasive development disorder. Since autism has been more recognized and diagnosed there was an initial spike in the number of cases, but even now with a pretty standard diagnosis there is gradual rise in ASD cases.

The common denominator of autism symptoms is misfiring of normal neuronal synapses. Many proteins, hormones, and genes that play a role in synapse are not working correctly in autism. It is difficult for them to connect longer synapses and shorter synapses tend to over fire

This is where the overstimulation comes into play. Because there is so much firing going on in one place it is difficult to connect the other synapses correctly. Many autistic people have a sensitivity to outside stimulants such as lights, sound, and movements.

They also have difficulty handling social situations and other people’s emotions. It is found that autistic people have lower levels of oxytocin. Oxytocin is known as the “love” hormone. It is produced during sex, childbirth, and breast feeding. During the first 6 months of a relationship there are elevated levels of oxytocin, this is the honeymoon stage.

Its emotional responses include trust, relaxation, and psychological stability. In response to stress oxytocin acts as an anxiolytic. People with higher levels of oxytocin are more extroverted and are more sensitive to other people’s emotions.

A small study was done on volunteers with mild ASD where they used oxytocin as a treatment. The oxytocin was taken as a nasal spray. The individuals were better able to handle social situations both at home, in public, and in a clinical setting.

After the success of that study they were given a grant to continue this research. Is this the new future for autistic people? Will they be able to change the social behavior of autistic people? How available will it be? Where do we draw the line, will people take oxytocin just to be more extroverted? Should everyone be more extroverted? With more research, who knows where this will lead us.

Disease/Health

Who Done It? When Vaccines Plead Not Guilty to Being the Source of Autism

Posted on April 26, 2016 by / 1 Comment

Autism is on the rise in the United States. The prevalence has increased from 1 in 110 in 2006 to 1 in 68 in 2010. This increase has led to more awareness surrounding the disease, as well as increased hype and concern.
Jenny McCarthy’s infamous campaign against vaccines as the culprit of her child’s autism has gained a lot of attention, and caused a “red scare” on vaccines.
This campaign, however, has been more detrimental to the health of the country than good. Outbreaks of diseases not seen since their vaccine development have caused detrimental consequences to children whose parent’s decided against vaccination.
Vaccines no longer contain the mercury that once was thought to cause autism—but the rate of autism diagnoses still increases. Thus, vaccines are not the culprit—the CDC confirms this. This then begs the question, what is?
Who Done It? Will We Ever Know?

(Won, H., Mah, W., Kim, E., 2013)

As one can observe from this lovely figure taken from this week’s research paper—the culprit lies in a mess of chemical signaling pathways. Not only can we not pinpoint exactly which red blob—the red are highlighted to signify that they are known to malfunction in autistic individuals—is responsible for autism, but this diagram doesn’t even account for all the variables.
There are considerations that need to be done about where in the brain the problem is occurring. The science points to the cerebellum and specifically in the Purkinje cells. However, there are also major differences that occur in autistic brains in various other structures—such as the hippocampus, corpus callosum, and amygdala.
Along with this, there are also environmental factors at play. There is a high metal sensibility in autistic brains—that cannot be traced to vaccines—but must be traced to something.
There are also neonatal concerns. Infection during pregnancy increases the risk of autism development in the child.
With all of these factors, the solution to the crime may never be solved.
What do we Now? The Evidence is Mounting.
Throughout the week we each investigated one of the red blobs. It seems that each plays a significant role in the development of autism, but each plays a different role that connects to other pathways, diseases, and complications.
Some of the more promising leads are pointing to Purkinje cell development in the cerebellum. These cells seem to over develop in the signal receiving end of the neuron—called the dendrite—while under developing in the signal sending regions—the axon.

(photo of Purkinje cell)

This results in loss of correct connections being made. The red blobs likely involved—that are likely to be caught “red handed”—are the neurexin and neurolignin connective proteins as well as the REK protein thought to guide axonal growth.
More evidence points to these culprits as the cerebellum’s functions are discovered. More and more, there are discoveries that link this stereotypical motor center with behavioral and social actions. If this is the case, the cerebellum and its Purkinje cells could be the eyewitnesses needed to point to the autism instigating culprit.
What will the penalty be? Treatment of ASD.
The culprit is on the verge of being caught. While the chemistry and brain functioning is complex, the story is continuously being uncovered. This leaves us with the judicial duty of questioning, what will we do once the culprit is identified?
We need to think critically about what autism is and what it is that is harmful about it. Yes, some behaviors that result from the disease are extremely harmful, and there is a lot to be said about the benefits of improving treatments.
However, there is a question about “odd” behavior and “bad” social skills. Should everyone be the same and have the same ability to interact? What is wrong with someone who doesn’t like to interact with others as much as they like to study art or science, for example?
By uncovering all there is to uncover about autism in the brain we run the risk of discovering what makes certain personalities develop over others. And this is a slippery slope.
Thus, this quest for who done it is one of pointing fingers instead of solving true problems. The autism scare must stop being about the hype, and start being about the science to treat the harmful aspects, while leaving room for individuality.

Health/Hot topics

Neurochemistry is Cool

Posted on April 25, 2016 by / 0 Comment

Signing up for the neurochemistry class was the best decision I made during registration week of the second semester of my senior year. First, I got my senior capstone credit, which was important at the time. But I was also glad that I had an opportunity to learn more about the brain, something that has always seemed like the most mysterious part of the human body or even all of life. I can’t say that really changed after taking a semester of neurochemistry, but it definitely shed a little light on it. I learned a ton of very interesting facts about the way the brain functions on a general level of neuronal connections and the chemistry involved, but I also learned quite a bit about the overall way that the brain works (what’s the neurochemistry good for without knowing the whole brain right?). The scientific aspect of the course was enjoyable and it has left me feeling like I know more than I really do, but sets me on the path to learn and discover more in the future.
The purely knowledge-based portion of the class was only half the fun. The other half was the communication of the scientific ideas that we discovered on our own or together through research and reading of complicated texts. This has been a great experience for me because it has taught me to communicate my ideas to other people more effective than I had been able to beforehand. There has never been a class that I have taken that has allowed the students to communicate so much and for so little consequence. In fact, we were rewarded grade-wise for talking, which made it even more enjoyable to get involved in the class. The “scientific communication” aspect of the course has instilled in me a greater confidence in my ability to work with other like-minded scientists, something that will undoubtedly, help me in my future career.
A lot of social factors were discussed while we talked about the different neurological disease, such as whether or not they should even be considered a disease of the brain in the first place (obesity and autism). Other things were not even science-related, such as how we can cope with loved ones or even ourselves developing a disease a debilitating and common as Alzheimer’s Disease is in the elderly. Most of us had personal ties with the topics discussed in class, which gave it a whole new level of meaning. This class has given me new awareness and understanding of people suffering from neurological and mental illnesses that I now partially understand from a neurochemical perspective, that that I can bypass and societal stigma attached to the diseases. This has made me an overall more well-rounded person, as we live in a society rampant with mental illnesses.
Overall, this class was fantastic and I would recommend it to anyone interested in science. Although it is small, it would do really well to be offered to everyone who cares about understanding the human body. Learning about the brain gives us a whole new perspective about the world we live in, with so many different and unique people existing around us.

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Autism and Autism Research On the Rise

Posted on April 25, 2016 by / 0 Comment

In the past decade the prevalence of autism has approximately doubled in diagnoses for children. In 2006, 1 in 110 children were diagnosed in the United States, and by 2010 it had increased to 1 in 68. For boys the diagnosis is much more common. The CDC states: “ASD is about 4.5 times more common among boys (1 in 42) than among girls (1 in 189)” (Found here). Experts say this is only partly because of a change in diagnosis criteria, and mostly because of some unknown factors in the way we live, the environment, or possibly something else.
The search for the cause of Autism has been a long and rigorous process, but not without its fruit. The vast amount of research for the developmental disorder has brought about knowledge of the disease that has related it in various ways to a dysfunction in the brain’s neurons from forming synaptic connections, much like schizophrenia. They are similar in that they are both now being considered brain development disorders, but they differ in their typical diagnosis age and symptoms: autism is diagnosed as a child, while schizophrenia symptoms usually develop in a person’s early 20s. The link between autism and schizophrenia include shared genetic risk factors, among other things. This is why it takes time to notice symptoms, because the development of the brain is apparently normal until certain parts of the brain continue to form their connections.
How a synapse is formed is dependent on many different molecules and genetic components that are found in neurons (these are cells in the brain that send electro-chemical signals that are responsible for the ability of the brain’s processing power). A synapse is the point of connection between two neurons that involve many different signal-chemicals (glutamate, dopamine and norepinephrine for example) and regulating-molecules such as GABA and enzymes. However, there are also physical structures that hold the neuronal synapses together, and chemicals that guide the direction of neurons to their proper locations to form new synapses. In autism, the processes involving all three of these factors: the chemical balance of signal and signal reception, the guidance of neurons, and the physical structures holding them together are though to be impaired because of chemical imbalances that exist since birth. During the first three years of life, those with autism have brain “overgrowth,” meaning that the number of neurons forming and neuronal connections it too high in certain areas of the brain.

Abnormal neuronal connections seen in brains of autism.

Knowing what we know about autism so far, it seems like there is a lot of knowledge about how we could treat the brain for healthy development, but treatment is still severely limited. The true underlying cause of autism remains unknown, however certain genetic and environmental risk factors have been identified. There is no evidence that vaccines cause autism, and many studies showing that they do not, as stated by the CDC, and backed up by many studies. Some examples of correlated causes of autism include certain precription drugs while pregnant (valproic acid and thalidomide), being born to older parents, or even stress during a pregnancy. The root cause remains elusive.

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Breaking down Autism

Posted on April 25, 2016 by / 0 Comment

Introduction to Autism
Autism spectrum disorder (ASD) is a group of various developmental disabilities defined by impaired social interaction and communication, characterized by subjects with narrow interests. However, biological mechanisms were not recognized with Autism until the 1980s, when studies demonstrated the high heritability of ASD and its connection with other genetic conditions. This provided compelling evidence for the role of genetics with Autism, and fueled research up to today on the neurologic causation of this disorder.
Diagnosis
Diagnosis of Autism spectrum disorder is based on the presence of two major symptoms: social-communication deficits and limited and repetitive interests/behaviors. These symptoms must be exhibited in early childhood, but additional symptoms include sensory and motor deficiencies, sleep disturbance, epilepsy, attention deficit/hyperactivity disorder, intellectual disability, anxiety and aggression. Autism prevalence has grown year to year for decades, with a prevalence of 1% worldwide today.
Genetics
It is widely understood ASD contains a huge genetic component. The concordance rates of autism are approximately 90% in monozygotic twins and 10% in dizygotic twins. However, Autism is rarely defined by a single genetic mutation, as these instances only account for 1-2% of Autism cases. Therefore, autism research has focused on genome-wide association studies, accounting for a wide range of genes and how multiple mutations can predispose Autism. Many recent discoveries relating to autism have been titled de novo mutations in genes that encode synaptic proteins and neuroligins. Additionally, several mutations of ASD are indicators for other psychological disorders such as intellectual disability, schizophrenia, childhood absence epilepsy, ADHD and depression.
Neuroanatomical Abnormalities
A common alteration in brain anatomy seen in about 20% of autistic children is macrocephaly, or overgrowth of the brain. Localized overgrowth and over-dendritic development has been identified in the frontrol lobe, parieto-temporal lobe, cerebellum, and subcortical limbic structures. Most notably, the cerebellum has is a main focus of neuroanatomical abnormalities in autistic subjects. Magnetic resonance imaging (MRI) have suggested hypoplasia throughout the cerebellum and most notably a reduction in Purkinje cells. Purkinje cell fibers have a very significant role in regulation of motor movements, helping the fluidity of all physical movement. Therefore, many autistic patients have sensory and motor dysfunctions. It has also been found that cerebellar activation is significantly reduced during selective attention tasks, whereas it is enhanced during a simple motor task in autistic individuals. Cerebellum dysfunction has also been shown to be associated with core symptoms of autism. Recent research has suggested Purkinje cells play a role in social functioning, and neurotransmitter communication throughout the brain. By finding this Purkinje cell role, the mechanism of autism spectrum disorder has further been clarified.
Neurotransmitter Abnormalities
Defects in excitatory/inhibitory balance throughout the brain occurs in patients with autism. Common defects in synaptic proteins in ASD leads to defective transmission in excitatory and inhibitory synapses, damaging the E-I balance throughout structures of the brain. Reduced levels of glutamate, an excitatory neurotransmitter, were observed in the plasma of autistic children, also indicated in post-mortem brains of autistic patients. Decreased levels of rate-limiting enzyme for synthesis of GABA was also observed in autistic brains, suggesting an excess of this inhibitory neurotransmitters.
Serotonin is a neurotransmitter known to play a role in regulating E-I balance. Increased levels of serotonin (5-HT) were observed in blood and urine of autistic individuals. Various genes encoding for serotonergic signaling are linked to autism, like the gene encoding for the serotonin transporter 5-HTT.
Lastly, proteins vital for pre-synaptic release are altered in autistic patients. Neurexins and neuroligins also regulate various aspects of both excitatory and inhibitory synaptic development and function. Many mutations in genes encoding neurexins and neuroligins have been associated with Autistic Spectrum disorder.
Overall, many complex neurological complications are present in autism, often stemming from genetic origin. By better understanding the factors in play in autism, one can better discern the nature of this condition, and become aware of psychological conditions.

Disease/Health

Autism Spectrum Disorder

Posted on April 25, 2016 by / 0 Comment

In a study between the years of 2006-2008, it was determined that 1 in 6 American children had a developmental disability ranging from the mild to more severe. These disabilities included anything from speech and language deficits to more serious disabilities like autism. Autism spectrum disorder is a developmental disorder characterized by difficulties in social interactions, communication, repetitive behaviors, motor coordination, and attentiveness.
While approximately 1 in 68 children are diagnosed with some form of autism spectrum disorder, it still isn’t known exactly what is underlying this condition. Recent research has attempted to compile the best theories on autism spectrum disorder in order to more fully explain how it directly impacts developing brains.

A network of cerebral proteins and substrates that might play a role in the development of autism spectrum disorder (Won et al.)
The most recent theory concerns a problem occurring along the connections between nerves called synapses. In brains of patients with autism spectrum disorder, it was shown that there is over-connectivity of neurons locally with less neurons that stretch between brain regions to aid in communication within the brain. It is hypothesized that an imbalance of excitement and inhibition nerve impulses in the brain could be preventing correct synapse formation leading to autism spectrum disorder.

Dopamine hyperactivity in the synapse could contribute to problems in autism spectrum disorder
Regardless of its cause, genetic or environmental, autism spectrum disorder is becoming more and more common and one thing that can be done is to raise awareness and support for those who are are suffering. Until more is discovered about autism spectrum disorder, the best we can do is offer to help support families and the search for a cure.

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Obesity and the Brain

Posted on April 17, 2016 by / 0 Comment

Hypothalamus
It has been recently discovered that unlike inflammation in the in the peripheral tissues, inflammation in the brain due to high fat intake occurs as soon as 1-3 days. In this time following a large fat intake, neuron damage is identified, and inflammatory symptoms spring throughout the hypothalamus. While most alterations are initially reversible, continued fat intake cause permanent damage to many structures like the mediobasal hypothalamus.
While weight gain is delayed, brain damage occurs immediately, shedding light on emerging studies today that portray obesity as a brain disease. Acutely inflamed hypothalamus due to short term over-nutrition or chronic obesity can become dysfunctional. This brain structure, responsible for regulating diet and caloric intake, might disrupt the precise coupling between energy intake and energy expenditure, fostering overeating and further weight gain.
Hippocampus
Recent articles have revealed conditions stemming from obesity-related conditions such as diabetes, hypertension, and cardiovascular disease are proven to adversely influence hippocampal size. High-fat diets induce pro-apoptotic (inflammatory) signaling such as expression of caspase-3 and gliosis throughout structures of the hippocampus. This local signaling of inflammation and cell death ultimately leads to hippocampal tissue loss. The hippocampus, responsible for countless cognitive functions, becomes severely impaired. Studies have shown both obesity and a high BMI in midlife are strong indicators of hippocampal degeneration in late life. Furthermore, factors such as high blood glucose levels have been linked to 10% volume change of the hippocampus within 1 year, regardless of factors such as age, sex, alcohol, and smoking.
Cognitive Decline
Obesity is associated with cognitive decline across the human life span. Often, these cognitive impairments are evident during child or adolescence, where deficits are seen in executive functioning, attention, and decreased intelligence quotient. Many studies have explored the possibility that deficient executive functioning leads to increased appetite, due to a loss of cognitive control of actions such as unhealthy eating.
Even healthy obese people show cognitive deficits in learning, memory, and executive function in contrast to non-obese individuals, which reflects the impacts of obesity. Cognitive performance declines with decreased physical activity and aerobic exercise, which are often linked to increased weight. These cognitive declines occur not only at the rudimentary or elementary level. Scholastic performance at collegiate and graduate levels have decline in response to obesity.
Not all cognitive losses are irreversible, however. Weight loss may result in rapid improvement in some cognitive functions. Studies have revealed improved memory following subjects undergoing bariatric surgery. Weight loss influences many variables, such as blood pressure, arterial flow, sleep quality and nutrition composition which all ultimately contribute to cognitive inclines.
Early Life
Exposure to excessive nutrition during vulnerable pre- and postnatal periods can impair the brain cognitively and disrupt brain-governed feeding behavior. Environments of over-nutrition are mediated many functional alterations which can lead to obesity, dysmetabolism and cognitive disadvantages throughout life.
Although caloric restriction can later reduce body weight gain, early life hypothalamic disposition to hyperphagia is irreversible. Maintaining a healthy diet accompanied by exercise for pregnant mothers is crucial for lifetime eating habits, as this period where feeding behavior is imprinted into the nucleus of the hypothalamus.