Pathophysiology underlying depressive-like behaviors and sleep disturbance

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430008
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Hiroshima University (2015-2016); Tokyo Medical and Dental University (2014)
• Principal Investigator: Aizawa Hidenori 広島大学, 医歯薬保健学研究院(医), 教授 (80391837)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: うつ病 / 睡眠 / モノアミン / 手綱核

Outline of Final Research Achievements

We examined the activity of neurons in habenular pathways and performed behavioral and sleep analyses in mice with pharmacological and genetic inhibition of the activity of the glial glutamate transporter GLT-1 in the LHb. The habenula-specific inhibition of GLT-1 increased the neuronal firing rate and the level of c-Fos expression in the LHb. Mice with reduced GLT-1 activity in the habenula exhibited a depressive-like phenotype in the tail suspension and novelty-suppressed feeding tests. These animals also displayed increased susceptibility to chronic stress, displaying more frequent avoidant behavior without affecting locomotor activity in the open-field test. Intriguingly, the mice showed disinhibition of rapid eye movement sleep, which is a characteristic sleep pattern in patients with depression. These results provide evidence that disrupting glutamate clearance in habenular astrocytes increases neuronal excitability and depressive-like phenotypes in behaviors and sleep.

Free Research Field

神経解剖学、神経生理学