Адам ағзасындағы Neuropeptide Y және оның қызметтері

Mammalian protein found in Homo sapiens

Neuropeptide Y (NPY) is a 36 amino acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. It is secreted alongside other neurotransmitters such as GABA and glutamate. In the autonomic system it is produced mainly by neurons of the sympathetic nervous system and serves as a strong vasoconstrictor and also causes growth of fat tissue. In the brain, it is produced in various locations including the hypothalamus, and is thought to have several functions, including: increasing food intake and storage of energy as fat, reducing anxiety and stress, reducing pain perception, affecting the circadian rhythm, reducing voluntary alcohol intake, lowering blood pressure, and controlling epileptic seizures.

Neuropeptide Y has been identified as being synthesized in GABAergic neurons and to act as a neurotransmitter during cellular communication. Neuropeptide Y is expressed in interneurons. NPY exerts most of its effects through Neuropeptide Y receptors, mainly Y1, Y2, Y4, and Y6. Subtypes Y1 and Y5 have known roles in the stimulation of feeding while Y2 and Y4 seem to have roles in appetite inhibition (satiety). Some of these receptors are among the most highly conserved neuropeptide receptors. High concentrations of neuropeptide Y synthesis and action have been found in the hypothalamus and hippocampus, specifically in the arcuate nucleus (ARC) and dentate gyrus. The arcuate nucleus has been found to have one of the highest concentrations of NPY. This allows NPY to regulate neuroendocrine release of various hypothalamic hormones such as luteinizing hormone. Neuropeptide Y1 receptors have been found in highest density in the dentate gyrus along with a variety of other brain areas. NPY is able to modulate the mitochondrial network by affecting the expression of many genes involved in mitochondrial functions and dynamics. It has been found that in breast muscle, ATP production genes (uncoupling protein, UCP; nuclear factor erythroid 2 like 2, NFE2L2) and a dynamics gene (mitofusin 1, MFN1) were upregulated (P < 0.05) at a low dose of NPY, while a high dose decreased (P < 0.05) markers of mitochondrial dynamics (mitofusin 2, MFN2; OPA1 mitochondrial dynamin like GTPase, OPA1) and increased (P < 0.05) genes involved in mitochondrial biogenesis (D loop, peroxisome proliferator activated receptor gamma, PPARG).

Neuropeptide Y has been indicated as playing an important role in neurogenesis in various parts of the brain. Two particular brain areas where NPY affects neurogenesis are the sub ventricular zone and the dentate gyrus of the hippocampus. These areas are where cell growth and proliferation occur into adulthood.

The dentate gyrus is significantly involved in cell proliferation, a process modulated by various internal factors including neuropeptide Y. Reduction or elimination of NPY released by interneurons decreased cell growth in this brain area. NPY affects neurogenesis by interacting with ERK kinase signaling pathways. Additionally, NPY acting on and stimulating Y1 receptors present on progenitor cell membranes in order to increase cell proliferation.

It was found that after blocking NPY expression in mouse olfactory epithelium, the amount of olfactory precursor cells decreased by half. This in turn caused the mice to develop a lower amount of olfactory cells overall. This study exemplified NPY's influence on precursor cells.

Following the isolation of neuropeptide Y (NPY) from the porcine hypothalamus in 1982, researchers began to speculate about the involvement of NPY in hypothalamic mediated functions. In a 1983 study, NPY ergic axon terminals were located in the paraventricular nucleus (PVN) of the hypothalamus, and the highest levels of NPY immunoreactivity was found within the PVN of the hypothalamus. Six years later, in 1989, Morris et al. homed in on the location of NPYergic nuclei in the brain. Furthermore, in situ hybridization results from the study showed the highest cellular levels of NPY mRNA in the arcuate nucleus (ARC) of the hypothalamus. In 1989, Haas & George reported that local injection of NPY into the PVN resulted in an acute release of corticotropin releasing hormone (CRH) in the rat brain, proving that NPYergic activity directly stimulates the release and synthesis of CRH. The latter became a hallmark paper in NPY studies. A significant amount of work had already been done in the 1970s on CRH and its involvement in stress and eating disorders such as obesity. These studies, collectively, marked the beginning for understanding the role of NPY in orexigenesis or food intake.

The role of neuropeptide Y has gained substantial attention for its involvement with alcoholism due to its diverse range of physiological effects. NPY neurons have been shown to interact with dopaminergic reward and emotion pathways in the nucleus accumbens and amygdala, respectively. NPY expression levels and alcohol preference have been shown to exhibit an inverse relationship. Expression levels are dependent on the brain area of interest. This indicates that baseline NPY levels could possibly influence innate alcohol preferences. As stated before, NPY levels and ethanol intake show an inverse relationship, therefore, increasing NPY availability could decrease alcohol intake. By creating a chemical antagonist for a Y2 receptor that would indirectly act as an agonist and stimulate Y1 receptors, alcohol consumption was successfully decreased in rats. Although, it has been shown that NPY gene expression, mRNA or neuropeptide levels are not influenced by long term alcohol consumption, but changes do occur during withdrawal from alcohol. These findings show that neuropeptide Y has varying effects on alcohol consumption. the common fruit fly has a neuropeptide that is similar to NPY, known as neuropeptide F. The levels of neuropeptide F are lowered in sexually frustrated male flies, and this causes the flies to increase their voluntary intake of alcohol.

Neuropeptide Y is considered to be an anxiolytic endogenous peptide and its levels can be modulated by stress. NPY has connections to the HPA axis and is believed to be necessary for stress modulation. It has been shown that higher levels of the Y1 and Y5 receptors in the amygdala result in reduced level of anxiety. Additionally, the Y1 receptor has been linked to anxiolytic effects in the forebrain while Y2 has been associated with the pons. and with dampening the fear response, allowing individuals to perform better under extreme stress. Studies of mice and monkeys show that repeated stress—and a high fat, high sugar diet—stimulate the release of neuropeptide Y, causing fat to build up in the abdomen. Researchers believe that by manipulating levels of NPY, they could eliminate fat from areas where it was not desired and accumulate at sites where it is needed.