TY - JOUR

T1 - Sex-specific behavioral and structural alterations caused by early-life stress in C57BL/6 and BTBR mice

AU - Reshetnikov, Vasiliy V.

AU - Ayriyants, Kseniya A.

AU - Ryabushkina, Yulia A.

AU - Sozonov, Nikita G.

AU - Bondar, Natalya P.

N1 - Funding Information: We are grateful to Nikita Khotskin and Oleg Shevelev for technical support during the processing of behavioral test data and during the MRI. This study was supported by State Budget Projects (Russia) # 0259-2021-0013 and Basic Russian Science Program АААА-А19-119100290012-8 . Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/9/24

Y1 - 2021/9/24

N2 - Lately, the development of various mental illnesses, such as depression, personality disorders, and autism spectrum disorders, is often associated with traumatic events in childhood. Nonetheless, the mechanism giving rise to this predisposition is still unknown. Because the development of a disease often depends on a combination of a genetic background and environment, we decided to evaluate the effect of early-life stress on BTBR mice, which have behavioral, neuroanatomical, and physiological features of autism spectrum disorders. As early-life stress, we used prolonged separation of pups from their mothers in the first 2 weeks of life (3 h once a day). We assessed effects of the early-life stress on juvenile (postnatal day 23) and adolescent (postnatal days 37–38) male and female mice of strains C57BL/6 (B6) and BTBR. We found that in both strains, the early-life stress did not lead to changes in the level of social behavior, which is an important characteristic of autism-related behavior. Nonetheless, the early-life stress resulted in increased locomotor activity in juvenile BTBR mice. In adolescent mice, the stress early in life caused a low level of anxiety in B6 males and BTBR females and increased exploratory activity in adolescent BTBR males and females. In addition, adolescent B6 male and female mice with a history of the early-life stress tended to have a thinner motor cortex as assessed by magnetic resonance imaging. As compared to B6 mice, BTBR mice showed reduced levels of social behavior and exploratory activity but their level of locomotor activity was higher. BTBR mice had smaller whole-brain, cortical, and dorsal hippocampal volumes; decreased motor cortex thickness; and increased ventral-hippocampus volume as compared to B6 mice, and these parameters correlated with the level of exploratory behavior of BTBR mice. Overall, the effects of early postnatal stress are sex- and strain-dependent.

AB - Lately, the development of various mental illnesses, such as depression, personality disorders, and autism spectrum disorders, is often associated with traumatic events in childhood. Nonetheless, the mechanism giving rise to this predisposition is still unknown. Because the development of a disease often depends on a combination of a genetic background and environment, we decided to evaluate the effect of early-life stress on BTBR mice, which have behavioral, neuroanatomical, and physiological features of autism spectrum disorders. As early-life stress, we used prolonged separation of pups from their mothers in the first 2 weeks of life (3 h once a day). We assessed effects of the early-life stress on juvenile (postnatal day 23) and adolescent (postnatal days 37–38) male and female mice of strains C57BL/6 (B6) and BTBR. We found that in both strains, the early-life stress did not lead to changes in the level of social behavior, which is an important characteristic of autism-related behavior. Nonetheless, the early-life stress resulted in increased locomotor activity in juvenile BTBR mice. In adolescent mice, the stress early in life caused a low level of anxiety in B6 males and BTBR females and increased exploratory activity in adolescent BTBR males and females. In addition, adolescent B6 male and female mice with a history of the early-life stress tended to have a thinner motor cortex as assessed by magnetic resonance imaging. As compared to B6 mice, BTBR mice showed reduced levels of social behavior and exploratory activity but their level of locomotor activity was higher. BTBR mice had smaller whole-brain, cortical, and dorsal hippocampal volumes; decreased motor cortex thickness; and increased ventral-hippocampus volume as compared to B6 mice, and these parameters correlated with the level of exploratory behavior of BTBR mice. Overall, the effects of early postnatal stress are sex- and strain-dependent.

KW - Adolescent mice

KW - BTBR

KW - C57Bl/6

KW - Early-life stress

KW - Juvenile mice

KW - Sex-specific effects

KW - Strain-specific effects

UR - http://www.scopus.com/inward/record.url?scp=85111305929&partnerID=8YFLogxK

U2 - 10.1016/j.bbr.2021.113489

DO - 10.1016/j.bbr.2021.113489

M3 - Article

C2 - 34303728

AN - SCOPUS:85111305929

VL - 414

SP - 113489

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

M1 - 113489

ER -