Nitric oxide, like many things in the body, is something that is beneficial to the body in small concentrations but also potentially harmful in larger concentrations. In small concentrations, nitric oxide is neurotransmitter and neuromodulator, and is important in certain signaling pathways in the brain. However, in larger concentration, nitric oxide (NO) is dangerous to the brain, causing cell death within the neurons. NO is found to be a player in “stroke, neurodegenerative disease, demyelination and neuroinflammatory diseases” (Pathologic role of glial nitric oxide in adult and pediatric neuroinflammatory diseases).
Nitric oxide formation is assisted by three enzymes, neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) (https://en.wikipedia.org/wiki/Nitric_oxide_synthase). nNOS is important for NO synthesis in the central and peripheral nervous system. eNOS is crucial to nitric oxide synthesis in the blood vessels, and is a regulator of the vessel’s function. The last enzyme, iNOS is, activated by NF-κB, and cytokines such as TNF-α and IL-1, and the over activation of this particular enzyme by these can lead to negative effects in the body. This activation of iNOS occurs largely in the astrocytes and in microglia, which can then lead to neuronal damage a death. Thus, as we see, when there is more nitric oxide being produced there is more neuronal death by the over activated microglia.
NO overproduction can lead to multiple sclerosis (MS) and neuroinflammatory diseases, which include periventricular leukomalacia (PVL), Krabbe’s disease, and X-linked adrenoleukodystrophy (ALD). MS occurs when the myelin protecting nerve cells in the CNS are damaged. This can lead to mental and physical problems including “autonomic, visual, motor and sensory problems” that “are determined by the locations of the lesions within the nervous system” (https://en.wikipedia.org/wiki/Multiple_sclerosis). PVL is a neuroinflammatory disease is “a form of white-matter brain injury, characterized by the white matter necrosis” or white matter death in the brain (Pathologic role of glial nitric oxide in adult and pediatric neuroinflammatory diseases). Krabbe’s disease is a genetic disease which slowly destroys the white matter in the brain and damages the myelin sheaths in the central nervous system. ALD is also a demyelinating disease, but much quicker and can lead to death within a couple years after onset, or another form will lead to slow axon degeneration and eventually paralysis in the legs.
Nitric oxide is a chemical that requires a very delicate balance within our bodies, as it is important in relation to the microglia and astrocytes, as when they work appropriately are good for the brain, but when over activated can lead to damage to neurons and some of the diseases mentioned above. In today’s world, there is always the fear of trying to stay at an ultra-healthy level, that we will do what it takes to protect ourselves from getting things like cancer or some of these diseases. However, these precautions don’t always make a difference, as it is hard to prevent these NO diseases, as sometimes we are genetically predisposed to them and there is not much we can do to protect ourselves. Sometimes the environment plays a role in contracting the disease, especially exposure to toxins in the NO case, but even then it is hard to ensure avoidance of things that we may encounter on a daily basis. Sometimes, rather than living in fear of contracting these diseases which can come from an array of sources, we just need to hope our bodies will do their best to protect themselves from imbalances.
Nitric Oxide: A Powerful Player in the Brain
