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This article, first published by Frontiers Media, is the author's final published version in Frontiers in Neuroanatomy, Volume 17, 2023, Article number 1190291.

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Copyright © 2023 Heng, Zigmond and Smeyne.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.


INTRODUCTION: As social animals, our health depends in part on interactions with other human beings. Yet millions suffer from chronic social isolation, including those in nursing/assisted living facilities, people experiencing chronic loneliness as well as those in enforced isolation within our criminal justice system. While many historical studies have examined the effects of early isolation on the brain, few have examined its effects when this condition begins in adulthood. Here, we developed a model of adult isolation using mice (C57BL/6J) born and raised in an enriched environment.

METHODS: From birth until 4 months of age C57BL/6J mice were raised in an enriched environment and then maintained in that environment or moved to social isolation for 1 or 3 months. We then examined neuronal structure and catecholamine and brain derived neurotrophic factor (BDNF) levels from different regions of the brain, comparing animals from social isolation to enriched environment controls.

RESULTS: We found significant changes in neuronal volume, dendritic length, neuronal complexity, and spine density that were dependent on brain region, sex, and duration of the isolation. Isolation also altered dopamine in the striatum and serotonin levels in the forebrain in a sex-dependent manner, and also reduced levels of BDNF in the motor cortex and hippocampus of male but not female mice.

CONCLUSION: These studies show that isolation that begins in adulthood imparts a significant change on the homeostasis of brain structure and chemistry.

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