Melatonin-Induced Postconditioning Suppresses NMDAR through Opening of the mPTP via Melatonin Receptor in Mouse Neurons

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09489
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Nara Medical University
• Principal Investigator: Nakagawa Ichiro 奈良県立医科大学, 医学部, 病院教授 (20550825)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: Meratonin / Postconditioning / patchclamp method

Outline of Final Research Achievements

Melatonin is a hormone that regulates circadian rhythms, but its neuroprotective effects have also attracted attention in recent years.
In this study, we investigated the effects of melatonin-induced PostC in mouse hippocampal pyramidal cells. Mice were used to compare control, melatonin-induced drug-induced PostC (melatonin group), melatonin receptor (MT) agonist, melatonin + MT inhibitor, and MT agonist + permission transition pore (mPTP) inhibitor groups.
Results showed that the melatonin group suppressed the rapid increase in sEPSC, and NMDA receptor currents were reduced in the melatonin and MT agonist groups, but not in the MT inhibitor combination group or the mPTP inhibitor combination group. Mitochondrial membrane potentials showed significantly higher rates of change in fluorescence ratios in the melatonin and MT agonist groups, indicating that melatonin reduces NMDA receptor activity through an MT-mediated mechanism, resulting in neuroprotective effects.

Free Research Field

神経虚血耐性

Academic Significance and Societal Importance of the Research Achievements

虚血耐性現象(PostC)は、致死的な虚血負荷の後に間欠的な虚血負荷を加え、再灌流後障害を抑制する現象である。メラトニンは概日リズムを調節するホルモンだが、その神経保護効果も近年注目されている。今回、マウスの海馬錐体細胞でメラトニン誘発性PostCの効果について検討した。本研究の結果メラトニンはsEPSCやNMDA誘導電流の増加、細胞質内Ca2+濃度上昇等を抑制して神経保護をもたらすことが分かった。さらにその機序がMT受容体やmPTPを介したものであり、ミトコンドリア膜電位の変化も関与していることが分かった。よってメラトニンはMTを介して神経保護効果をもたらすことが示された。