Brain facts

Do we have an anxiolytic neuromodulator?

Today I will talk again about the neuromodulators used by the brain (you can find a quick description of what a neuromodulator is here and a description of serotonin, oxytocin, adrenaline and dopamine by clicking on their names) and I will write about the neuropeptide Y (NPY), the most abundant neuropeptide in the brain that, among many other functions, is an extremely potent stimulator of feeding behaviour and acts as an anxiolytic during stressful situations.

As I just mentioned above, NPY is one of the most abundant neuropeptides in the brain and periphery and co-localizes with a variety of neurotransmitters (such as GABA or glutamate). It has an important role in many physiological functions that range over energy homeostasis, food intake, circadian rhythm, stress response and cognition. These many functions of NPY are related to its expression in different brain areas, as for example the hypothalamic arcuate nucleus or the locus coeruleus. NPY is also a marker peptide for a specific class of GABAergic interneurons in the cortex and hippocampus, where NPY-positive interneurons built local circuits that control the activity of principal cells and thereby affect, for example, emotional memory formation.

This neuropeptide is known to be an extremely potent stimulator of feeding behaviour that can be blocked by injections that prevent the NPY action. Moreover, a study in genetically obese rats to demonstrated the role of NPY in eating disorders such as obesity, where chronically elevated levels of NPY can be seen.

NPY is considered to be an anxiolytic endogenous peptide and its levels can be modulated by stress. Indeed, the stress response determines an increase in anxiety that can be reduced via NPY-mediated anxiolysis, as several studies show. Moreover, higher levels of NPY may be associated with resilience (an ability to recover from or adjust easily to misfortune or change, from against and recovery from posttraumatic stress disorder (PTSD, a mental disorder that a person can develop when exposed to a traumatic experience) and with decreasing the fear response, allowing individuals to perform better under extreme stress (see schematic below). Many studies are currently exploring the role of NPY in PTSD, particularly military research centers, as most people who experience a traumatic event do not develop PTSD, however, as we could all imagine, this emotional disorder has an higher incidence among soldiers.

Schematics of possible causes and behavioural manifestations, linked to NPY impaired functions, that can lead to posttraumatic stress disorder (PTSD). Modified from “Neuropeptide Y (NPY) and posttraumatic stress disorder (PTSD): A translational update” by Schmeltzer et al., 2016. DOI: 10.1016/j.expneurol.2016.06.020

Lastly, I would like to briefly mention the involvement of NPY in alcoholism.  A study demonstrated how NPY levels and ethanol intake show an inverse relationship, thus increasing NPY availability could decrease alcohol intake. Indeed, the administration of NPY was found to reduce binge-drinking behaviour. However, as it always happens in research, to better understand the function of gene, protein or hormone, scientists create individuals that do not produce it, in order to verify the differences in behaviour compared to the individuals that have produce it. Therefore, researchers created knock-out mice (a genetically modified mouse in which an existing gene was inactivated –or “knocked down”- by disrupting it with an artificial piece of DNA) and they were able to see a higher voluntary intake of alcohol and a higher resistance to alcohol’s sedating effects, compared to normal mice.

To sum up, due to its variegated effects on behaviour, its many locations in different brain areas and its abundance, more effort and research need to be done in order to pinpoint with a higher degree of confidence the many actions of NPY.

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