TY - JOUR

T1 - Stress early in life leads to cognitive impairments, reduced numbers of CA3 neurons and altered maternal behavior in adult female mice

AU - Reshetnikov, Vasiliy V.

AU - Kovner, Anna V.

AU - Lepeshko, Arina A.

AU - Pavlov, Konstantin S.

AU - Grinkevich, Larisa N.

AU - Bondar, Natalya P.

N1 - Publisher Copyright: © 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/3/1

Y1 - 2020/3/1

N2 - The hippocampus is a crucial part of the limbic system involved both in cognitive processing and in the regulation of responses to stress. Adverse experiences early in life can disrupt hippocampal development and lead to impairment of the hypothalamic-pituitary-adrenal axis response to subsequent stressors. In our study, two types of early-life stress were used: prolonged separation of pups from their mothers (for 3 hours/day, maternal separation, MS) and brief separation (for 15 minutes/day, handling, HD). In the first part of our study, we found that adult female mice (F0) who had experienced MS showed reduced locomotor activity and impairment of long-term spatial and recognition memory. Analysis of various hippocampal regions showed that MS reduced the number of mature neurons in CA3 of females, which is perhaps a crucial hippocampal region for learning and memory; however, neurogenesis remained unchanged. In the second part, we measured maternal care in female mice with a history of early-life stress (F0) as well as the behavior of their adult offspring (F1). Our results indicated that MS reduced the level of maternal care in adult females (F0) toward their own progeny and caused sex-specific changes in the social behavior of adult offspring (F1). In contrast to MS, HD had no influence on female behavior or hippocampal plasticity. Overall, our results suggest that prolonged MS early in life affects the adult behavior of F0 female mice and hippocampal neuronal plasticity, whereas the mothers' previous experience has effects on the behavior of their F1 offspring through disturbances of mother-infant interactions.

AB - The hippocampus is a crucial part of the limbic system involved both in cognitive processing and in the regulation of responses to stress. Adverse experiences early in life can disrupt hippocampal development and lead to impairment of the hypothalamic-pituitary-adrenal axis response to subsequent stressors. In our study, two types of early-life stress were used: prolonged separation of pups from their mothers (for 3 hours/day, maternal separation, MS) and brief separation (for 15 minutes/day, handling, HD). In the first part of our study, we found that adult female mice (F0) who had experienced MS showed reduced locomotor activity and impairment of long-term spatial and recognition memory. Analysis of various hippocampal regions showed that MS reduced the number of mature neurons in CA3 of females, which is perhaps a crucial hippocampal region for learning and memory; however, neurogenesis remained unchanged. In the second part, we measured maternal care in female mice with a history of early-life stress (F0) as well as the behavior of their adult offspring (F1). Our results indicated that MS reduced the level of maternal care in adult females (F0) toward their own progeny and caused sex-specific changes in the social behavior of adult offspring (F1). In contrast to MS, HD had no influence on female behavior or hippocampal plasticity. Overall, our results suggest that prolonged MS early in life affects the adult behavior of F0 female mice and hippocampal neuronal plasticity, whereas the mothers' previous experience has effects on the behavior of their F1 offspring through disturbances of mother-infant interactions.

KW - cognition

KW - early-life stress

KW - handling

KW - hippocampus

KW - learning

KW - maternal care

KW - maternal separation

KW - memory

KW - neurogenesis

KW - neuronal plasticity

KW - CHILDHOOD MALTREATMENT

KW - SOCIAL STRESS

KW - ELEVATED PLUS-MAZE

KW - SYNAPTIC PLASTICITY

KW - CARE

KW - MEDIAL PREOPTIC AREA

KW - MEMORY

KW - SEPARATION

KW - DENTATE GYRUS

KW - HIPPOCAMPAL NEUROGENESIS

UR - http://www.scopus.com/inward/record.url?scp=85059094524&partnerID=8YFLogxK

U2 - 10.1111/gbb.12541

DO - 10.1111/gbb.12541

M3 - Article

C2 - 30488555

AN - SCOPUS:85059094524

VL - 19

JO - Genes, Brain and Behavior

JF - Genes, Brain and Behavior

SN - 1601-1848

IS - 3

M1 - e12541

ER -