4.4 Article

Inhibition of adult neurogenesis reduces avoidance behavior in male, but not female, mice subjected to early life adversity

Journal

NEUROBIOLOGY OF STRESS
Volume 17, Issue -, Pages -

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.ynstr.2022.100436

Keywords

Adult neurogenesis; Dentate gyrus; Hippocampus; Stress; Early life adversity; Anxiety

Categories

Funding

  1. NIMH [R01MH117459-01]
  2. NSF GRFP [2021318039]

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Early life adversity increases the risk of developing neuropsychiatric illnesses, and adult neurogenesis may play a role in buffering against the detrimental stress-induced outcomes. This study suggests that there may be sex differences in the role of adult-born neurons in regulating behavior changes induced by early life adversity.
Early life adversity (ELA) increases the risk of developing neuropsychiatric illnesses such as anxiety disorders. However, the mechanisms connecting these negative early life experiences to illness later in life remain unclear. In rodents, plasticity mechanisms, specifically adult neurogenesis in the ventral hippocampus, have been shown to be altered by ELA and important for buffering against detrimental stress-induced outcomes. The current study sought to explore whether adult neurogenesis contributes to ELA-induced changes in avoidance behavior. Using the GFAP-TK transgenic model, which allows for the inhibition of adult neurogenesis, and CD1 littermate controls, we subjected mice to an ELA paradigm of maternal separation and early weaning (MSEW) or control rearing. We found that mice with intact adult neurogenesis showed no behavioral changes in response to MSEW. After reducing adult neurogenesis, however, male mice previously subjected to MSEW had an unexpected decrease in avoidance behavior. This finding was not observed in female mice, suggesting that a sex difference exists in the role of adult-born neurons in buffering against ELA-induced changes in behavior. Taken together with the existing literature on ELA and avoidance behavior, this work suggests that strain differences exist in susceptibility to ELA and that adult-born neurons may play a role in regulating adaptive behavior.

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