PINK1 deficiency is associated with increased deficits of adult hippocampal neurogenesis and lowers the threshold for stress-induced depression in mice.

PINK1 deficiency is associated with increased deficits of adult hippocampal neurogenesis and lowers the threshold for stress-induced depression in mice.
Behav Brain Res. 2019 Feb 05;:
Authors: Agnihotri SK, Sun L, Yee BK, Shen R, Akundi RS, Zhi L, Duncan MJ, Cass WA, Büeler H
Abstract
Parkinson's disease (PD) is characterized by motor impairments and several non-motor features, including frequent depression and anxiety. Stress-induced deficits of adult hippocampal neurogenesis (AHN) have been linked with abnormal affective behavior in animals. It has been speculated that AHN defects may contribute to affective symptoms in PD, but this hypothesis remains insufficiently tested in animal models. Mice that lack the PD-linked kinase PINK1 show impaired differentiation of adult-born neurons in the hippocampus. Here, we examined the relationship between AHN deficits and affective behavior in PINK1-/- mice under basal (no stress) conditions and after exposure to chronic stress. PINK1 loss and corticosterone negatively and jointly affected AHN, leading to lower numbers of neural stem cells and newborn neurons in the dentate gyrus of corticosterone-treated PINK1-/- mice. Despite increased basal AHN deficits, PINK1-/- mice showed normal affective behavior. However, lack of PINK1 sensitized mice to corticosterone-induced behavioral despair in the tail suspension test at a dose where wildtype mice were unaffected. Moreover, after two weeks of ch...

Source: Behavioural Brain Research - February 5, 2019 Category: Neurology Authors: Agnihotri SK, Sun L, Yee BK, Shen R, Akundi RS, Zhi L, Duncan MJ, Cass WA, Büeler H Tags: Behav Brain Res Source Type: research