If we think of research like a giant puzzle, it is easy to get excited when new information is discovered, when a few pieces are connected. But this doesn’t erase the fact that many pieces have yet to be found, whether that is underneath the couch, behind the door, or as with many literal research labs, behind more research.
Several adult and pediatric neuroinflammatory diseases are no exception to this analogy.
Nitric Oxide (NO) is a key neurotransmitter and neuromodulator that plays a role in a wide range of neuronal activity throughout the central nervous system. The particular enzymes that help synthesis nitric oxide within the body have three different subtypes (neuronal nitric oxide substrate (nNOS), endothelial nitric oxide substrate (eNOS), and inducible nitric oxide substrate (iNOS)).
Unfortunately with excessive amounts of nitric oxide in the central nervous system, there can be consequences. With normal amounts of nitric oxide involving nNOS, regulation of synaptic signaling and plasticity between neurons occurs. However, with excessive amounts of NO, this can lead to neuronal toxicity, apoptosis and cell death. eNOS acts as a crucial regulator of cardiovascular homeostasis. When NO is synthesized, regulation of the blood vessels occurs, which maintains an anti-proliferative and anti-apoptotic environment. Unfortunately, as with almost all neurotransmitters and neuromodulators, the right amount is key, as excessive or low amounts can cause permanent damage.
The particular substrate of iNOS has been a valuable topic of interest for its potential role in neuroinflammatory diseases in research. iNOS release of NO has a large involvement in regards to immune responses.
Side note: *It is important to know that the role of glial cells (cells that help protect and provide support to neurons), play a very critical role in the development of the brain.
Now to attempt and connect the puzzle pieces…
In regards to three neuroinflammatory diseases, there may be a link between the function of glial cells and their interaction with nitric oxide.
In Periventricular leukomalacia (PVL), this disease is characterized by white matter premature death, which can lead to cerebral palsy and cognitive deficits in premature infants. According to the article our class read, there may be two possible causes: lack of oxygen or blood flow OR damage to the glial cells. Research has shown that nitric oxide damages developing oligodendrocytes (a type of glial cell).
In Krabbe’s disease, a fatal degenerative and neuroinflammatory disorder, is one that impacts the myelin sheath of the nervous system. Observations in research has shown that psychosine (a type of glycosphingolipid), which accumulates in particular in Krabbe’s disease, “under inflammatory conditions leads to the iNOS-mediated NO overproduction, which in turn may play a role in the pathogenesis of this disease.”
With the relationship between NO and glial cells, it is important to keep in mind the whole picture, instead of focusing on a few pieces (even as crucial as those few pieces may be). Researchers know that the “iNOS overexpression is not the only mechanism by which glial cells can affect neuronal function.” There are obviously more pieces to be discovered, but researchers are hopeful that the understanding of the complexities behind the involvement of NO can be a first step.
Nitric Oxide: Another piece of the puzzle?
