Activation of Neuropeptide Y2 Receptor Can Inhibit Global Cerebral Ischemia-Induced Brain Injury.

Abstract

Cardiopulmonary arrest (CA) can greatly impact a patient's life, causing long-term disability and death. Although multi-faceted treatment strategies against CA have improved survival rates, the prognosis of CA remains poor. We previously reported asphyxial cardiac arrest (ACA) can cause excessive activation of the sympathetic nervous system (SNS) in the brain, which contributes to cerebral blood flow (CBF) derangements such as hypoperfusion and, consequently, neurological deficits. Here, we report excessive activation of the SNS can cause enhanced neuropeptide Y levels. In fact, mRNA and protein levels of neuropeptide Y (NPY, a 36-amino acid neuropeptide) in the hippocampus were elevated after ACA-induced SNS activation, resulting in a reduced blood supply to the brain. Post-treatment with peptide YY3-36 (PYY3-36), a pre-synaptic NPY2 receptor agonist, after ACA inhibited NPY release and restored brain circulation. Moreover, PYY3-36 decreased neuroinflammatory cytokines, alleviated mitochondrial dysfunction, and improved neuronal survival and neurological outcomes. Overall, NPY is detrimental during/after ACA, but attenuation of NPY release via PYY3-36 affords neuroprotection. The consequences of PYY3-36 inhibit ACA-induced 1) hypoperfusion, 2) neuroinflammation, 3) mitochondrial dysfunction, 4) neuronal cell death, and 5) neurological deficits. The present study provides novel insights to further our understanding of NPY's role in ischemic brain injury.

• Authors: Reggie Hui-Chao Lee, Celeste Yin-Chieh Wu, Cristiane T Citadin, Alexandre Couto E Silva, Harlee E Possoit, Garrett A Clemons, Christina H Acosta, Victoria A de la Llama, Jake T Neumann, Hung Wen Lin
• Journal: Neuromolecular medicine (Neuromolecular Med) Vol. 24 Issue 2 Pg. 97-112 (06 2022) ISSN: 1559-1174 [Electronic] United States
• PMID: 34019239 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Neuropeptide Y
• Receptors, Neuropeptide Y
• neuropeptide Y2 receptor

Topics

• Animals
• Brain Injuries (etiology)
• Brain Ischemia (complications)
• Heart Arrest (complications, metabolism)
• Neuropeptide Y (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Neuropeptide Y (agonists, genetics)