Stress induced microglial activation contributes to depression

Pharmacological Research, Journal Year: 2022, Volume and Issue: 179, P. 106145 - 106145

Published: Feb. 24, 2022

Language: Английский

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The role of neuroinflammation in PV interneuron impairments in brain networks; implications for cognitive disorders

Reviews in the Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Fast spiking parvalbumin (PV) interneuron is an inhibitory gamma-aminobutyric acid (GABA)ergic diffused in different brain networks, including the cortex and hippocampus. As a key component of PV interneurons collaborate fundamental functions such as learning memory by regulating excitation inhibition (E/I) balance generating gamma oscillations. The unique characteristics interneurons, like their high metabolic demands long branching axons, make them too vulnerable to stressors. Neuroinflammation one most significant stressors that have adverse, long-lasting impact on interneurons. affects through specialized inflammatory pathways triggered cytokines tumor necrosis factor (TNF) interleukin 6 (IL-6). crucial cells neuroinflammation, microglia, also play role. destructive effect inflammation can comprehensive effects cause neurological disorders schizophrenia, Alzheimer’s disease (AD), autism spectrum disorder (ASD), bipolar disorder. In this article, we provide review mechanisms which neuroinflammation leads hypofunction these diseases. integrated knowledge about role cognitive networks involved impairment pathology diseases help us with better therapeutic interventions.

Language: Английский

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Parvalbumin interneuron mGlu5 receptors govern sex differences in prefrontal cortex physiology and binge drinking

Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 49(12), P. 1861 - 1871

Published: May 21, 2024

Language: Английский

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Gene Expression has Distinct Associations with Brain Structure and Function in Major Depressive Disorder

Advanced Science, Journal Year: 2023, Volume and Issue: 10(7)

Published: Jan. 13, 2023

Major depressive disorder (MDD) is associated with structural and functional brain abnormalities. MDD as well anatomy function are influenced by genetic factors, but the role of gene expression remains unclear. Here, this work investigates how cortical contributes to abnormalities in MDD. This compares gray matter volume resting-state measures a Chinese sample 848 patients 749 healthy controls, these case-control differences then variation expression. While whole positively abnormalities, it negatively observes relationships levels for individual genes, found that transcriptional correlates structure show opposite relations dysregulation postmortem tissue from patients. further identifies genes or related The MDD-related enriched tissue, cells, biological pathways. These findings suggest distinct mechanisms underlie MDD, highlight importance development

Language: Английский

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Neurogenesis-independent mechanisms of MRI-detectable hippocampal volume increase following electroconvulsive stimulation

Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 49(8), P. 1236 - 1245

Published: Jan. 9, 2024

Abstract Electroconvulsive therapy (ECT) is one of the most effective psychiatric treatments but underlying mechanisms are still unclear. In vivo human magnetic resonance imaging (MRI) studies have consistently reported ECT-induced transient hippocampal volume increases, and an animal model ECT (electroconvulsive stimulation: ECS) was shown to increase neurogenesis. However, a causal relationship between neurogenesis MRI-detectable increases following has not been verified. this study, mice were randomly allocated into four groups, each undergoing different number ECS sessions (e.g., 0, 3, 6, 9). T2-weighted images acquired using 11.7-tesla MRI. A whole brain voxel-based morphometry analysis conducted identify any ECS-induced changes. Additionally, histological examination with super-resolution microscopy investigate microstructural changes in regions that showed ECS. Furthermore, parallel experiments performed on X-ray-irradiated ECS-related As result, we revealed for first time induced MRI-detectable, dose-dependent mice. increased volumes seen even lacking neurogenesis, suggesting required increase. The comprehensive analyses identified excitatory synaptic density ventral CA1 as major contributor observed Our findings demonstrate modification structures rather than may be biological mechanism ECT/ECS-induced

Language: Английский

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Neurobiological mechanisms of electroconvulsive therapy for depression: Insights into hippocampal volumetric increases from clinical and preclinical studies

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 18, 2024

Abstract Depression is a highly prevalent and disabling psychiatric disorder. The hippocampus, which plays central role in mood regulation memory, has received considerable attention depression research. Electroconvulsive therapy (ECT) the most effective treatment for severe pharmacotherapy‐resistant depression. Although working mechanism of ECT remains unclear, recent magnetic resonance imaging (MRI) studies have consistently reported increased hippocampal volumes following ECT. clinical implications these volumetric increases specific cellular molecular significance are not yet fully understood. This narrative review brings together evidence from animal models human to provide detailed examination In particular, our preclinical MRI research using mouse model consistent with findings, demonstrating marked increase volume Notable changes were observed ventral CA1 region, including dendritic growth synaptic density at excitatory synapses. Interestingly, inhibition neurogenesis did affect ECT‐related detected on MRI. However, it unclear whether histological would be correlated effect Hence, future relationships between changes, brain antidepressant could benefit bidirectional translational approach that integrates models. Such may important insights into mechanisms potential biomarkers associated ECT‐induced thereby advancing understanding

Language: Английский

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Gephyrin phosphorylation facilitates sexually dimorphic development and function of parvalbumin interneurons in the mouse hippocampus

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(8), P. 2510 - 2526

Published: March 19, 2024

The precise function of specialized GABAergic interneuron subtypes is required to provide appropriate synaptic inhibition for regulating principal neuron excitability and synchronization within brain circuits. Of these, parvalbumin-type (PV neuron) dysfunction a feature several sex-biased psychiatric disorders, although, the underlying developmental mechanisms are unclear. While transcriptional action sex hormones generates sexual dimorphism during development, whether kinase signaling contributes differences in PV remains unexplored. In hippocampus, we report that gephyrin, main inhibitory post-synaptic scaffolding protein, phosphorylated at serine S268 S270 developmentally-dependent manner both males females. When examining Gphn

Language: Английский

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Impact of stress on inhibitory neuronal circuits, our tribute to Bruce McEwen

Neurobiology of Stress, Journal Year: 2022, Volume and Issue: 19, P. 100460 - 100460

Published: May 13, 2022

This manuscript is dedicated to the memory of Bruce S. McEwen, commemorate impact he had on how we understand stress and neuronal plasticity, profound influence exerted our scientific careers. The focus this review stressors inhibitory circuits, particularly those limbic system, but also consider other regions affected by these adverse experiences. We revise effects acute chronic during different stages development lifespan, taking into account sex animals. first physiology neurons expression molecules related directly GABAergic neurotransmission, then specific interneuron subpopulations, parvalbumin somatostatin expressing cells. Then analyze structures plasticity neurons: polysialylated form neural cell adhesion molecule perineuronal nets. Finally, potential antidepressants or environmental manipulations revert circuits.

Language: Английский

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Repeated stress gradually impairs auditory processing and perception

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(2), P. e3003012 - e3003012

Published: Feb. 11, 2025

Repetitive stress, a common feature of modern life, is major risk factor for psychiatric and sensory disorders. Despite the prevalence perceptual abnormalities in these disorders, little known about how repetitive stress affects processing perception. Here, we combine mice, longitudinal measurement cortical activity, auditory-guided behaviors to test if sound perception neutral sounds adults are modulated by stress. We found that alters processing, increasing spontaneous activity while dampening sound-evoked responses pyramidal PV cells heightening SST cells. These alterations auditory culminated shifts, particularly reduction loudness Additionally, our work reveals impact on evolves gradually as stressor persists over time, emphasizing dynamic evolving nature this mechanism. Our findings provide insight into possible mechanism which behavior, challenging idea primarily modulates emotionally charged stimuli.

Language: Английский

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Molecular neurobiology of loss: a role for basolateral amygdala extracellular matrix

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(11), P. 4729 - 4741

Published: Aug. 29, 2023

Abstract Psychological loss is a common experience that erodes well-being and negatively impacts quality of life. The molecular underpinnings are poorly understood. Here, we investigate the mechanisms using an environmental enrichment removal (ER) paradigm in male rats. basolateral amygdala (BLA) was identified as region interest, demonstrating differential Fos responsivity to ER having established role stress processing adaptation. A comprehensive multi-omics investigation BLA, spanning multiple cohorts, platforms, analyses, revealed alterations microglia extracellular matrix (ECM). Follow-up studies indicated decreased size, complexity, phagocytosis, suggesting reduced immune surveillance. Loss also substantially increased ECM coverage, specifically targeting perineuronal nets surrounding parvalbumin interneurons, plasticity inhibition within BLA following loss. Behavioral analyses suggest these effects linked impaired salience evaluation, leading mismatch between stimulus reaction intensity. These loss-like behaviors could be rescued by depleting during period, helping us understand underlying revealing novel targets ameliorate its impact.

Language: Английский

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