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The effects of maternal separation on behaviours under social-housing environments in adult male C57BL/6 mice.

ABSTRACT: Adverse experience in early life can affect the formation of neuronal circuits during postnatal development and exert long-lasting influences on neural functions that can lead to the development of a variety of psychiatric disorders including depression, anxiety disorders, and post-traumatic stress disorder. Many studies have demonstrated that daily repeated maternal separation, an animal model of early-life stress, can induce impairments in emotional behaviours and cognitive function during adolescence and adulthood. However, the behavioural phenotypes of maternally separated mice under long-term group-housing conditions are largely unknown. In this study, we applied our newly developed assay system to investigate the effects of maternal separation on behaviours under group-housing conditions during four days of continuous observations. Using our system, we found that repeated maternal separation resulted in inappropriate social distance from cagemates, altered approach preferences to others, and induced a lower rank in the time spent on the running wheel under group-housing conditions in adult male mice. Focussing on these behavioural abnormalities that appear in an environment with a social context will be important insights to understand the pathogenesis of psychiatric disorders.

SUBMITTER: Endo N

PROVIDER: S-EPMC7804413 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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The effects of maternal separation on behaviours under social-housing environments in adult male C57BL/6 mice.

Endo Nozomi N Makinodan Manabu M Mannari-Sasagawa Takayo T Horii-Hayashi Noriko N Somayama Nami N Komori Takashi T Kishimoto Toshifumi T Nishi Mayumi M

Scientific reports 20210112 1

Adverse experience in early life can affect the formation of neuronal circuits during postnatal development and exert long-lasting influences on neural functions that can lead to the development of a variety of psychiatric disorders including depression, anxiety disorders, and post-traumatic stress disorder. Many studies have demonstrated that daily repeated maternal separation, an animal model of early-life stress, can induce impairments in emotional behaviours and cognitive function during ado ...[more]

PMID: 33436833

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Project description:IntroductionAdolescence is a critical period in cognitive and emotional development, characterized by high levels of social interaction and increases in risk-taking behavior including binge drinking. Adolescent exposure to social stress and binge ethanol have individually been associated with the development of social, emotional, and cognitive deficits, as well as increased risk for alcohol use disorder. Disruption of cortical development by early life social stress and/or binge drinking may partly underlie these enduring emotional, cognitive, and behavioral effects. The study goal is to implement a novel neighbor housing environment to identify the effects of adolescent neighbor housing and/or binge ethanol drinking on (1) a battery of emotional and cognitive tasks (2) adult ethanol drinking behavior, and (3) the nucleus accumbens and prefrontal cortex transcriptome.MethodsAdolescent male and female C57BL/6J mice were single or neighbor housed with or without access to intermittent ethanol. One cohort underwent behavioral testing during adulthood to determine social preference, expression of anxiety-like behavior, cognitive performance, and patterns of ethanol intake. The second cohort was sacrificed in late adolescence and brain tissue was used for transcriptomics analysis.ResultsAs adults, single housed mice displayed decreased social interaction, deficits in the novel object recognition task, and increased anxiety-like behavior, relative to neighbor-housed mice. There was no effect of housing condition on adolescent or adult ethanol consumption. Adolescent ethanol exposure did not alter adult ethanol intake. Transcriptomics analysis revealed that adolescent housing condition and ethanol exposure resulted in differential expression of genes related to synaptic plasticity in the nucleus accumbens and genes related to methylation, the extracellular matrix and inflammation in the prefrontal cortex.DiscussionThe behavioral results indicate that social interaction during adolescence via the neighbor housing model may protect against emotional, social, and cognitive deficits. In addition, the transcriptomics results suggest that these behavioral alterations may be mediated in part by dysregulation of transcription in the frontal cortex or the nucleus accumbens.

Project description:Adolescence is a critical period in cognitive and emotional development, characterized by high levels of social interaction and increases in risk-taking behavior including binge drinking. Adolescent exposure to social stress and binge ethanol have individually been associated with the development of social, emotional, and cognitive deficits, as well as increased risk for alcohol use disorder. Disruption of cortical development by early life social stress and/or binge drinking may partly underlie these enduring emotional, cognitive, and behavioral effects. The study goal is to implement a novel neighbor housing environment to identify the effects of adolescent neighbor housing and/or binge ethanol drinking on (1) a battery of emotional and cognitive tasks (2) adult ethanol drinking behavior, and (3) the nucleus accumbens and prefrontal cortex transcriptome. Adolescent male and female C57BL/6J mice were single or neighbor housed with or without access to intermittent ethanol. One cohort underwent behavioral testing during adulthood to determine social preference, expression of anxiety-like behavior, cognitive performance, and patterns of ethanol intake. The second cohort was sacrificed in late adolescence and brain tissue was used for transcriptomics analysis. As adults, single housed mice displayed decreased social interaction, deficits in the novel object recognition task, and increased anxiety-like behavior, relative to neighbor-housed mice. There was no effect of housing condition on adolescent or adult ethanol consumption. Adolescent ethanol exposure did not alter adult ethanol intake. Transcriptomics analysis revealed that adolescent housing condition and ethanol exposure resulted in differential expression of genes related to synaptic plasticity in the nucleus accumbens and genes related to methylation, the extracellular matrix and inflammation in the prefrontal cortex. The behavioral results indicate that social interaction during adolescence via the neighbor housing model may protect against emotional, social, and cognitive deficits. In addition, the transcriptomics results suggest that these behavioral alterations may be mediated in part by dysregulation of transcription in the frontal cortex or the nucleus accumbens

Project description:This study explores the effects of maternal separation as a chronic early life stress (ELS) on pancreatic islets insulin content and secretion, and their potential relationship with the hippocampus insulin content and spatial memory in young adulthood. Male rat offspring were divided into two groups: stress (STR) and non-stress (non-STR) groups. The animals of the STR group were separated from their mothers during postnatal days (PND) 1 to 21. During the weaning time, that is, PND-0 to PND-21, the body weight and length of the pups were measured. Blood samples were collected on PND-1, 21, 29 and 34 and during young adulthood (53±2 days) to determine plasma corticosterone and insulin levels. The young adult animals were also tested for spatial memory. One day after the memory test, the animals were decapitated and their pancreases were removed to measure the islets insulin content and secretion. Finally, the animals' hippocampi were isolated to determine their insulin content and insulin receptor protein amounts. During the period of weaning, the body weight and length of pups belonging to the STR group were significantly lower as compared to those in the non-STR group. Maternal separation did not change the plasma levels of insulin but increased plasma corticosterone levels from PND-21 to young adulthood and also reduced the islets insulin content but did not affect insulin secretion and the hippocampus insulin content and insulin receptor protein amount. Although, at the end of the memory tests, rats of the STR group reached the escape box at almost the same time and distance and with the same errors as rats of the non-STR group, the distance traveled to reach the escape box showed a steep reduction in the non-STR group as compared to the STR group after the first trial. Moreover, as compared to the STR group, the non-STR group showed an increasing trend for direct strategy to find the escape box. The islets insulin content and secretion, and the plasma insulin concentration were not significantly correlated with the hippocampus insulin content. From the results of the present study, it appears that the main behavioral effect of the maternal separation stress in the spatial memory task was to impair the strategy used by the animals to reach the escape box. This may indicate that maternal separation stress affects brain regions other than the hippocampus. Moreover, due to the reduction of the body weight and length of offspring belonging to the STR group, it should be further considered that both maternal separation and early life malnutrition are directly (and mechanistically) linked to cognitive alterations later in life in ways that are not dependent on peripheral and hippocampal insulin content.

Dataset Information

The effects of maternal separation on behaviours under social-housing environments in adult male C57BL/6 mice.

Publications

The effects of maternal separation on behaviours under social-housing environments in adult male C57BL/6 mice.

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