TY - JOUR
T1 - The estrous cycle modulates early-life adversity effects on mouse avoidance behavior through progesterone signaling
AU - Laham, Blake J.
AU - Murthy, Sahana S.
AU - Hanani, Monica
AU - Clappier, Mona
AU - Boyer, Sydney
AU - Vasquez, Betsy
AU - Gould, Elizabeth
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Early-life adversity (ELA) increases the likelihood of neuropsychiatric diagnoses, which are more prevalent in women than men. Since changes in reproductive hormone levels can also increase the probability of anxiety disorders in women, we examined the effects of ELA on adult female mice across the estrous cycle. We found that during diestrus, when progesterone levels are relatively high, ELA mice exhibit increased avoidance behavior and increased theta oscillation power in the ventral hippocampus (vHIP). We also found that diestrus ELA mice had higher levels of progesterone and lower levels of allopregnanolone, a neurosteroid metabolite of progesterone, in the vHIP compared with control-reared mice. Progesterone receptor antagonism normalized avoidance behavior in ELA mice, while treatment with a negative allosteric modulator of allopregnanolone promoted avoidance behavior in control mice. These results suggest that altered vHIP progesterone and allopregnanolone signaling during diestrus increases avoidance behavior in ELA mice.
AB - Early-life adversity (ELA) increases the likelihood of neuropsychiatric diagnoses, which are more prevalent in women than men. Since changes in reproductive hormone levels can also increase the probability of anxiety disorders in women, we examined the effects of ELA on adult female mice across the estrous cycle. We found that during diestrus, when progesterone levels are relatively high, ELA mice exhibit increased avoidance behavior and increased theta oscillation power in the ventral hippocampus (vHIP). We also found that diestrus ELA mice had higher levels of progesterone and lower levels of allopregnanolone, a neurosteroid metabolite of progesterone, in the vHIP compared with control-reared mice. Progesterone receptor antagonism normalized avoidance behavior in ELA mice, while treatment with a negative allosteric modulator of allopregnanolone promoted avoidance behavior in control mice. These results suggest that altered vHIP progesterone and allopregnanolone signaling during diestrus increases avoidance behavior in ELA mice.
UR - http://www.scopus.com/inward/record.url?scp=85143535874&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85143535874&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-35068-w
DO - 10.1038/s41467-022-35068-w
M3 - Article
C2 - 36476469
AN - SCOPUS:85143535874
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 7537
ER -