New publication on a novel gene causing depressive-like behaviors

Image by David Mark from Pixabay

We have just published a paper which identified a novel gene Pcsk5 acting on immune reaction in the mouse brain. Chronic stress activated this gene, which led to the subsequent activation of the other genes MMPs causing remodeling of the extracellular matrix. Since immune cell such as monocyte and microglia started to be activated and move more actively upon remodeling of extracellular matrix, Neurons seems to produce Pcsk5 seems to induce neuroinflammation in response to the chronic stress.

Our publication in the Neuropsychopharmacology

Press release from Hiroshima University

Press release from AMED

Interestingly, this protein turned out to be localize to the small area in the brain called habenula. This region attracts a surge of interest according to its role in regulation of central monoaminergic system. Monoamines such as dopamine and serotonin are known to be a basis of pathophysiology of depression and pharmacological action of antidepressant available currently. Since this area is excited when the animal perceives disappointment and punishment, it is proposed that the habenula may act as a negative source of reinforcement signal in the brain to control our behavioral strategy for survival.

Chronic hyper-activation of the habenula via PCSK5-MMP signaling pathway

Taking the current results into consideration, we may begin to understand how the transient activation of the habenula via punishment or disappointment can be chronic via changes in extracellular environment.

#Neurobiology #Hiroshima #Brain #神経 #広島 #脳

Hidenori Aizawa
Hidenori Aizawa

Principal investigator in Neurobiology lab in Hiroshima. His research interests include brain machinery underlying the pathophysiology of psychiatric and neurological disorders.

Hikaru Ito
Hikaru Ito
Associate professor

Dr. Ito worked for the altered glial activity in the limbic area as a basis of depressive-like behaviors in mice. He is currently an associate professor in Kagawa University.

Kanako Nozaki
Kanako Nozaki
Assistant professor

Dr. Nozaki worked for a role of mitochondrial protein TSPO in depressive-like behaviors in mice. She is currently an assitant professor in Yamaguchi University.