Dentate Gyrus Microstructure Is Associated With Resilience After Exposure to Maternal Stress Across Two Human Cohorts

Dijk, Milenna T. van; Talati, Ardesheer; Kashyap, Pratik; Desai, Karan; Kelsall, Nora; Gameroff, Marc J.; Aw, Natalie; Abraham, Eyal; Cullen, Breda; Cha, Jiook; Anacker, Christoph; Weissman, Myrna M.; Posner, Jonathan

doi:10.1016/j.biopsych.2023.06.026

Cited by 4 publications

(2 citation statements)

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“…25–31 Abnormalities in hippocampal microstructure and volume are also found in human subjects at high familial risk for depression 32,33 and in children with a history of ELA. 31,34–36 Hippocampal impairments resulting from ELA, including reduced neurogenesis, may thus predispose to heightened vulnerability for developing psychiatric disorders later in life.…”

Section: Introductionmentioning

confidence: 99%

“…23,24 ELA causes several alterations in the structure and cellular composition of the rodent DG, including decreases in dendritic arborization, neurogenesis, granule cell numbers, and overall DG volume. 25–31 Abnormalities in hippocampal microstructure and volume are also found in human subjects at high familial risk for depression 32,33 and in children with a history of ELA. 31,34–36 Hippocampal impairments resulting from ELA, including reduced neurogenesis, may thus predispose to heightened vulnerability for developing psychiatric disorders later in life.…”

Section: Introductionmentioning

confidence: 99%

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Resilience to Early Life Adversity Effects on Stress Reactivity by Postnatal Knockdown of 5-HT_1AAutoreceptors

Dixon,

Malave,

Thompson

et al. 2024

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Early Life Adversity (ELA) predisposes to stress hypersensitivity in adulthood, but neurobiological mechanisms that can protect from long-lasting effects of ELA are poorly understood. Serotonin 1A (5HT1A) autoreceptors in the raphé nuclei regulate adult stress vulnerability, but if 5HT1Acould be targeted to prevent ELA effects on susceptibility to future stressors is unknown. Here, we exposed mice with postnatal knockdown of 5HT1Aautoreceptors to the limited bedding and nesting model of ELA from postnatal day (P)3-10. We then tested behavioral, neuroendocrine, neurogenic, and neuroinflammatory responses to an acute swim stress in male and female mice in adolescence (P35) and in adulthood (P56). In ELA-exposed females, adult swim stress exposure increased passive coping and despair-like behavior, corticosterone levels at baseline and after stress, and neuronal activity and corticotropin releasing hormone levels in the paraventricular nucleus of the hypothalamus. ELA also reduced neurogenesis and increased microglia activation in the ventral dentate gyrus (DG) of the hippocampus – an important mediator of individual differences in stress susceptibility. These effects of ELA were specific to females, but not males, and manifested predominantly in adulthood, but not earlier on in adolescence. Postnatal 5HT1Aautoreceptor knockdown prevented ELA effects on stress reactivity and on neurogenesis and neuroinflammation in the DG, indicating that reducing 5HT1Aautoreceptors confers resilience to ELA. Our findings demonstrate that ELA induces long-lasting and sex-specific impairments in stress reactivity and ventral DG function across development, and identify 5HT1Aautoreceptors as potential targets to prevent these persistent effects of ELA.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Resilience to Early Life Adversity Effects on Stress Reactivity by Postnatal Knockdown of 5-HT_1AAutoreceptors

Dixon,

Malave,

Thompson

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

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Maternal Stress and Vulnerability in Offspring: Hippocampal Mechanisms of Resilience

van Rooij,

Powers

2024

Biological Psychiatry

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Through a teratological lens: A narrative review of exposure to stress and drugs of abuse during pregnancy on neurodevelopment

Willford,

Kaufman

2024

Neurotoxicology and Teratology

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Dentate Gyrus Microstructure Is Associated With Resilience After Exposure to Maternal Stress Across Two Human Cohorts

Cited by 4 publications

References 102 publications

Resilience to Early Life Adversity Effects on Stress Reactivity by Postnatal Knockdown of 5-HT_1AAutoreceptors

Resilience to Early Life Adversity Effects on Stress Reactivity by Postnatal Knockdown of 5-HT_1AAutoreceptors

Maternal Stress and Vulnerability in Offspring: Hippocampal Mechanisms of Resilience

Through a teratological lens: A narrative review of exposure to stress and drugs of abuse during pregnancy on neurodevelopment

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Dentate Gyrus Microstructure Is Associated With Resilience After Exposure to Maternal Stress Across Two Human Cohorts

Cited by 4 publications

References 102 publications

Resilience to Early Life Adversity Effects on Stress Reactivity by Postnatal Knockdown of 5-HT1AAutoreceptors

Resilience to Early Life Adversity Effects on Stress Reactivity by Postnatal Knockdown of 5-HT1AAutoreceptors

Maternal Stress and Vulnerability in Offspring: Hippocampal Mechanisms of Resilience

Through a teratological lens: A narrative review of exposure to stress and drugs of abuse during pregnancy on neurodevelopment

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Product

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Resilience to Early Life Adversity Effects on Stress Reactivity by Postnatal Knockdown of 5-HT_1AAutoreceptors

Resilience to Early Life Adversity Effects on Stress Reactivity by Postnatal Knockdown of 5-HT_1AAutoreceptors