Agonistic analog of growth hormone-releasing hormone promotes neurofunctional recovery and neural regeneration in ischemic stroke.

Abstract

Ischemic stroke can induce neurogenesis. However, most stroke-generated newborn neurons cannot survive. It has been shown that MR-409, a potent synthetic agonistic analog of growth hormone-releasing hormone (GHRH), can protect against some life-threatening pathological conditions by promoting cell proliferation and survival. The present study shows that long-term treatment with MR-409 (5 or 10 μg/mouse/d) by subcutaneous (s.c.) injection significantly reduces the mortality, ischemic insult, and hippocampal atrophy, and improves neurological functional recovery in mice operated on for transient middle cerebral artery occlusion (tMCAO). Besides, MR-409 can stimulate endogenous neurogenesis and improve the tMCAO-induced loss of neuroplasticity. MR-409 also enhances the proliferation and inhibits apoptosis of neural stem cells treated with oxygen and glucose deprivation-reperfusion. The neuroprotective effects of MR-409 are closely related to the activation of AKT/CREB and BDNF/TrkB pathways. In conclusion, the present study demonstrates that GHRH agonist MR-409 has remarkable neuroprotective effects through enhancing endogenous neurogenesis in cerebral ischemic mice.

• Authors: Yueyang Liu, Jingyu Yang, Xiaohang Che, Jianhua Huang, Xianyang Zhang, Xiaoxiao Fu, Jialing Cai, Yang Yao, Haotian Zhang, Ruiping Cai, Xiaomin Su, Qian Xu, Fu Ren, Renzhi Cai, Andrew V Schally, Ming-Sheng Zhou
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 118 Issue 47 (11 23 2021) ISSN: 1091-6490 [Electronic] United States
• PMID: 34782465 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bdnf protein, mouse
• Brain-Derived Neurotrophic Factor
• Creb1 protein, mouse
• Cyclic AMP Response Element-Binding Protein
• Membrane Glycoproteins
• Neuroprotective Agents
• Growth Hormone-Releasing Hormone
• Ntrk2 protein, mouse
• Protein-Tyrosine Kinases

Topics

• Animals
• Apoptosis (drug effects)
• Brain-Derived Neurotrophic Factor (metabolism)
• Cell Proliferation (drug effects)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Growth Hormone-Releasing Hormone (agonists, genetics, metabolism)
• Infarction, Middle Cerebral Artery (metabolism)
• Ischemic Stroke (metabolism)
• Male
• Membrane Glycoproteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Nerve Regeneration (drug effects)
• Neural Stem Cells (metabolism)
• Neurogenesis (drug effects)
• Neuronal Plasticity
• Neuroprotective Agents
• Protein-Tyrosine Kinases (metabolism)
• Recovery of Function (drug effects)