Transient impairment in microglial function causes sex-specific deficits in synaptic maturity and hippocampal function in mice exposed to early adversity

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 122, P. 95 - 109

Published: Aug. 10, 2024

Abnormal development and function of the hippocampus are two most consistent findings in humans rodents exposed to early-life adversity (ELA), with males often being more affected than females. Using limited bedding (LB) paradigm as a rodent model ELA, we found that male adolescent mice had been LB exhibit significant deficits contextual fear conditioning synaptic connectivity hippocampus, which not observed This is linked altered developmental refinement connectivity, severely impairing microglial-mediated pruning female pups on postnatal day 17 (P17), but P33 when levels engulfment by microglia substantially lower. Since undergoes intense during second third weeks life, investigated whether required for behavioral aberrations mice. Indeed, transient ablation from P13-21 normally developing caused sex-specific abnormalities similar those Furthermore, chemogenetic activation same period reversed phagocytic at P17 restored normal Our data support an additional contribution astrocytes effects LB, increased expression membrane receptor MEGF10 enhanced hippocampal 17-day-old females, littermates. These suggest potential compensatory mechanism may explain relative resilience Collectively, our study highlights novel role glial cells mediating mouse ELA.

Language: Английский

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Stress-induced reduction of Na ⁺ /H ⁺ exchanger isoform 1 promotes maladaptation of neuroplasticity and exacerbates depressive behaviors

Science Advances, Journal Year: 2022, Volume and Issue: 8(45)

Published: Nov. 11, 2022

Major depression disorder (MDD) is a neuropsychiatric characterized by abnormal neuronal activity in specific brain regions. A factor that crucial maintaining normal functioning intracellular pH (pHi) homeostasis. In this study, we show chronic stress, which induces depression-like behaviors animal models, down-regulates the expression of hippocampal Na+/H+ exchanger isoform 1, NHE1, major determinant pHi neurons. Knockdown NHE1 CA1 pyramidal neurons leads to acidification, promotes dendritic spine loss, lowers excitatory synaptic transmission, and enhances susceptibility stress exposure rats. Moreover, E3 ubiquitin ligase cullin4A may promote ubiquitination degradation induce these effects an unbalanced on processes. Electrophysiological data further suggest excitability caused maladaptation neuroplasticity be involved pathogenesis disease. These findings elucidate mechanism for homeostasis alteration as related MDD.

Language: Английский

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Site-Specific knockdown of microglia in the locus coeruleus regulates hypervigilant responses to social stress in female rats

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 109, P. 190 - 203

Published: Jan. 20, 2023

Language: Английский

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Association between depression status in adolescents and cognitive performance over the subsequent six years: A longitudinal study

Journal of Affective Disorders, Journal Year: 2023, Volume and Issue: 329, P. 105 - 112

Published: Feb. 17, 2023

Language: Английский

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Topological network properties of resting-state functional connectivity patterns are associated with metal mixture exposure in adolescents

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Feb. 6, 2023

Introduction Adolescent exposure to neurotoxic metals adversely impacts cognitive, motor, and behavioral development. Few studies have addressed the underlying brain mechanisms of these metal–associated developmental outcomes. Furthermore, metal occurs as a mixture, yet previous most often consider each individually. In this cross–sectional study, we investigated relationship between topological metrics in adolescents. Methods 193 participants (53% females, ages: 15–25 years) enrolled Public Health Impact Metals Exposure (PHIME) measured concentrations four (manganese, lead, copper, chromium) multiple biological media (blood, urine, hair, saliva) acquired resting–state functional magnetic resonance imaging scans. Using graph theory metrics, computed global local efficiency (global:GE; local:LE) 111 areas (Harvard Oxford Atlas). We used weighted quantile sum (WQS) regression models examine association mixtures metric (GE or LE), adjusted for sex age. Results observed significant negative associations mixture GE LE [βGE = −0.076, 95% CI (−0.122, −0.031); βLE= −0.051, (−0.095, −0.006)]. Lead chromium blood contributed GE, while hair LE. Discussion Our results suggest that during adolescence reduces integrating information networks at both levels, informing potential neural toxicity metals. further are due combined joint effects different metals, rather than single metal.

Language: Английский

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Association between gut permeability, brain volume, and cognition in healthy participants and patients with schizophrenia spectrum disorder

Brain and Behavior, Journal Year: 2023, Volume and Issue: 13(6)

Published: April 24, 2023

Abstract Introduction The barrier function of the gut is important for many organs and systems, including brain. If permeability increases, bacterial fragments may enter circulation, giving rise to increased systemic inflammation. Increases in translocation are reflected higher values blood markers, lipopolysaccharide binding protein (LBP) soluble cluster differentiation 14 (sCD14). Some pioneer studies showed a negative association between markers brain volumes, but this remains scarcely investigated. We investigate effect on volumes cognition both healthy controls patients with schizophrenia spectrum disorder (SSD). Materials methods Healthy ( n = 39) SSD 72) underwent an MRI‐scan, venipuncture assessments. investigated associations LBP sCD14 (intracranial volume, total hippocampal volume) using linear regression. then associated cognitive mediation analysis, intracranial volume as mediator. Results b –0.11, p .04), –0.25, .07). Both were indirectly lower functioning (LBP: –0.071, .028; sCD14: –0.213, .052), mediated by low volume. In patients, these markedly less present. Conclusion These findings extend earlier suggesting that negatively affect which impacts cognition, even young group. replicated, finding stresses importance development optimal Absence group indicate other factors such allostatic load, chronic medication use interrupted educational carrier had larger impact attenuated relative contribution translocation.

Language: Английский

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Sex Differences in Response-Contingent Cannabis Vapor Administration During Adolescence Mediate Enduring Effects on Behavioral Flexibility and Prefrontal Microglia Activation in Rats

Cannabis and Cannabinoid Research, Journal Year: 2024, Volume and Issue: 9(4), P. e1184 - e1196

Published: Jan. 8, 2024

Cannabis is the most used illicit drug in United States. With many states passing legislation to permit its recreational use, there concern that cannabis use among adolescents could increase dramatically coming years. Historically, it has been difficult model real-world investigate causal relationship between adolescence and behavioral neurobiological effects adulthood.

Language: Английский

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Transient Impairment in Microglial Function Causes Sex-Specific Deficits in Synaptic and Hippocampal Function in Mice Exposed to Early Adversity

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 15, 2024

Abnormal development and function of the hippocampus are two most consistent findings in humans rodents exposed to early life adversity, with males often being more affected than females. Using limited bedding (LB) paradigm as a rodent model we found that male adolescent mice had been LB exhibit significant deficits contextual fear conditioning synaptic connectivity hippocampus, which not observed This is linked altered developmental refinement connectivity, severely impairing microglial-mediated pruning female pups on postnatal day 17 (P17), but P33 when levels engulfment by microglia substantially lower. Since undergoes intense during second third weeks life, investigated whether required for behavioral aberrations mice. Indeed, transient ablation from P13-21, normally developing caused sex-specific abnormalities similar those Furthermore, chemogenetic activation same period reversed phagocytic at P17 restored normal Our data support an additional contribution astrocytes effects LB, increased expression membrane receptor MEGF10 enhanced hippocampal 17-day-old females, littermates. finding suggests potential compensatory mechanism may explain relative resilience Collectively, these studies highlight novel role glial cells mediating mouse early-life adversity.

Language: Английский

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Apoptosis-induced decline in hippocampal microglia mediates the development of depression-like behaviors in adult mice triggered by unpredictable stress during adolescence

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 978, P. 176763 - 176763

Published: June 20, 2024

Language: Английский

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Sex and Region-Specific Differences in Microglial Morphology and Function Across Development

Neuroglia, Journal Year: 2025, Volume and Issue: 6(1), P. 2 - 2

Published: Jan. 4, 2025

Microglia are exceptionally dynamic resident innate immune cells within the central nervous system, existing on a continuum of morphologies and functions throughout their lifespan. They play vital roles in response to injuries infections, clearing cellular debris, maintaining neural homeostasis development. Emerging research suggests that microglia strongly influenced by biological factors, including sex, developmental stage, local environment. This review synthesizes findings sex differences microglial morphology function key brain regions, frontal cortex, hippocampus, amygdala, hypothalamus, basal ganglia, cerebellum, across Where available, we examine how gonadal hormones influence these characteristics. Additionally, highlight limitations relying solely infer underscore need for comprehensive, multimodal approaches guide future research. Ultimately, this aims advance dialogue spatiotemporally heterogeneous implications vulnerability neurological psychiatric disorders.

Language: Английский

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