A Balancing Act: How Nitric Oxide Can Keep Your Neurons Happy
The saying “you can’t have too much of a good thing” might hold true when you want to convince yourself to have another slice of cake and watch “just one more” episode of Love is Blind on Netflix or stay up for “just a few more minutes” to scroll through social media; but before you know it, it’s three o’clock in the morning, you have a stomach-ache from too much sugar, and have to wake up at 6 am for work. Clearly, the opposite is true, and you can have too much of a good thing, which is also true for some molecular processes within the human body.
Many molecular processes function to maintain a delicate balance within the body, which is called homeostasis. Too much or too little of a protein, hormone, or by-product from metabolism can cause an imbalance in the body, which needs to be compensated to ensure that cellular processes continue to function appropriately. In the brain, some of these functions include the production of chemicals called neurotransmitters that turn neuronal activity on or turn off. One specific neurotransmitter called glutamate is the main neurotransmitter in the brain that causes neurons to turn on and become active. Although glutamate is necessary to stimulate neuronal activity, too much glutamate – much like eating too much cake, can make neurons sick and contribute to the development of neurodegenerative diseases.
Figure. Gracing the cover of the journal Glia volume 70 issue 5 is a microscopy image taken by Dr. Vasiliki Tellios, of Bergman glia (green), one of the types of supporting cells in the cerebellum, wrapping around the fine branches of Purkinje neurons (magenta), which are the primary neurons in the cerebellum. Within the cerebellum, nitric oxide is an important molecule that helps Bergmann glia properly support Purkinje neurons.
Specifically, cerebellar ataxias are a type of neurological disorder that affects the part of the brain involved in movement control – the cerebellum – and is characterized by an inability to coordinate fine motor movements that can lead to slurred speech, poor hand-eye coordination, shuffled gate while walking, as well as balance issues. Cerebellar ataxias can occur from acquired brain injuries or inherited from genetics with a prevalence of roughly one to four individuals for every 100,000 people worldwide. Specifically, the beloved 90’s TV personality and science educator – Bill Nye the Science Guy is a carrier of a hereditary form of ataxia, which runs in the Nye family. Importantly, some cerebellar ataxias are characterised by elevated levels of glutamate, which contributes to the disease symptoms.
Research from the University of Western Ontario conducted by Dr. Vasiliki Tellios examined how supporting cells within the brain – called glia – regulate the amount of glutamate that is available to activate neurons within the cerebellum. Specifically, Dr. Tellios studied the function and activity of a subtype of glia called Bergmann glia, which is a type of supporting cell that exists only in the cerebellum. The experiments performed by Dr. Tellios examined how these cells regulate the amount of glutamate that is available to activate the main type of neurons in the cerebellum – called Purkinje Neurons.
This research study, published in the journal Glia demonstrated that a gaseous molecule called nitric oxide – which is produced by Bergman glia – helps these supporting cells remove excess glutamate from surrounding Purkinje neurons in order to maintain proper Purkinje neuron function and activity. Importantly, Dr Tellios determined that when the ability to produce nitric oxide is removed from Bergmann glia, these cells are not as efficient at removing excessive glutamate from surrounding Purkinje neurons. Additionally, when Dr. Tellios and her team inspected slices of cerebellar brain tissue under a microscope, they observed that when Bergman glia were able to produce nitric oxide, the surrounding Purkinje neurons looked like large trees with many healthy articulating branches, while when Bergmann glia were unable to produce nitric oxide, the surrounding Purkinje neurons appeared like sickly bushes with thick and stubby branches. Clearly, having too much of a good thing – like glutamate – can in fact be bad. You can think of Bergmann glia as that internal dialogue you have when you are contemplating on eating another slice of cake. When nitric oxide is present, that inner dialogue is successful at convincing you to put away that extra slice of cake and prevents you from having a stomach-ache; much like that extra slice of cake, when Bergman glia successfully remove glutamate from the environment, the Purkinje neurons remain healthy and undamaged.
Understanding the intricacies of how neurons and supporting cells communicate and function together is important to understand the inner workings of the brain. Research that focuses on the supporting cells of the brain, such as this study by Dr. Tellios, is crucial to fully understand the cause of cerebellar ataxias, which could later contribute to the development of therapeutic targets that improve abnormal interactions between neurons and these supporting cells.
Original article Link: Tellios, V., Maksoud, M.J.E, Lu, W.Y. The expression and function of glutamate aspartate transporters in Bergmann glia are decreased in neuronal nitric oxide synthase-knockout mice during postnatal development. Glia. (2022) 1-17.