Two Weeks of Variable Stress Increases Gamma-H2AX Levels in the Mouse Bed Nucleus of the Stria Terminalis

Publication date: 1 March 2018 Source:Neuroscience, Volume 373 Author(s): Brendan D. Hare, Tina M. Thornton, Mercedes Rincon, Borivoj Golijanin, S. Bradley King, Diane M. Jaworski, William A. Falls Recent reports demonstrate that DNA damage is induced, and rapidly repaired, in circuits activated by experience. Moreover, stress hormones are known to slow DNA repair, suggesting that prolonged stress may result in persistent DNA damage. Prolonged stress is known to negatively impact physical and mental health; however, DNA damage as a factor in stress pathology has only begun to be explored. Histone H2A-X phosphorylated at serine 139 (γH2AX) is a marker of DNA double-strand breaks (DSB), a type of damage that may lead to cell death if unrepaired. We hypothesized that a 14-day period of variable stress exposure sufficient to alter anxiety-like behavior in male C57BL/6J mice would produce an increase in γH2AX levels in the bed nucleus of the stria terminalis (BNST), a region implicated in anxiety and stress regulation. We observed that 14 days of variable stress, but not a single stress exposure, was associated with increased levels of γH2AX 24 h after termination of the stress paradigm. Further investigation found that phosphorylation levels of a pair of kinases associated with the DNA damage response, glycogen synthase kinase 3 β (GSK3β) and p38 mitogen-activated protein kinase (MAPK) were also elevated following variable stress. Our results suggest that unrepa...

Source: Neuroscience - February 6, 2018 Category: Neuroscience Source Type: research