Distinct mechanisms of allopregnanolone and diazepam underlie neuronal oscillations and differential antidepressant effect

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Jan. 8, 2024

The rapid relief of depressive symptoms is a major medical requirement for effective treatments disorder (MDD). A decrease in neuroactive steroids contributes to the pathophysiological mechanisms associated with neurological MDD. Zuranolone (SAGE-217), steroid that acts as positive allosteric modulator synaptic and extrasynaptic δ-subunit-containing GABA receptors, has shown rapid-onset, clinically antidepressant action patients MDD or postpartum depression (PPD). Benzodiazepines, on other hand, act modulators receptors but are not approved treatment It remains unclear how differences molecular contribute alleviation regulation neuronal activity. Focusing antidepressant-like effects activity basolateral amygdala (BLA) medial prefrontal cortex (mPFC), we conducted head-to-head comparison study allopregnanolone benzodiazepine diazepam using mouse social defeat stress (SDS) model. Allopregnanolone exhibited interaction test SDS mice. This effect was abolished receptor δ-subunit knockout mice (δko mice) subjected same protocol. Regarding neurophysiological mechanism these effects, increased theta oscillation BLA increase did occur δko Consistent this, potentiated tonic inhibition interneurons via receptors. Theta mPFC also by diazepam. Finally, frontal electroencephalography recordings naïve Neuronal network alterations showed decreased beta depressed These results demonstrated that, unlike benzodiazepines, through activation this change Our findings support notion distinctive may

Language: Английский

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Perineuronal Net Alterations Following Early-Life Stress: Are Microglia Pulling Some Strings?

Biomolecules, Journal Year: 2024, Volume and Issue: 14(9), P. 1087 - 1087

Published: Aug. 30, 2024

The extracellular matrix plays a key role in synapse formation and the modulation of synaptic function central nervous system. Recent investigations have revealed that microglia, resident immune cells brain, are involved remodeling under both physiological pathological conditions. Moreover, dysregulation innate responses has been documented stress-related psychopathologies as well relation to early-life stress. However, dynamics microglial regulation ECM how it can be impacted by adversity understudied. This brief review provides an overview recent literature on this topic, drawing from animal model human post mortem studies. Direct indirect mechanisms through which microglia may regulate matrix-including perineuronal nets-are presented discussed light interactions with other cell types.

Language: Английский

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Sex- and exposure age-dependent effects of adolescent stress on ventral tegmental area dopamine system and its afferent regulators

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(2), P. 611 - 624

Published: Oct. 12, 2022

Language: Английский

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microRNA-dependent regulation of gene expression in GABAergic interneurons

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

Published: May 5, 2023

Information processing within neuronal circuits relies on their proper development and a balanced interplay between principal local inhibitory interneurons those circuits. Gamma-aminobutyric acid (GABA)ergic are remarkably heterogeneous population, comprising subclasses based morphological, electrophysiological, molecular features, with differential connectivity activity patterns. microRNA (miRNA)-dependent post-transcriptional control of gene expression represents an important regulatory mechanism for plasticity. miRNAs large group small non-coding RNAs (21-24 nucleotides) acting as negative regulators mRNA translation stability. However, while miRNA-dependent regulation in neurons has been described heretofore several studies, understanding the role is only beginning to emerge. Recent research demonstrated that differentially expressed interneuron subclasses, vitally migration, maturation, survival during embryonic crucial cognitive function memory formation. In this review, we discuss recent progress function. We aim shed light onto mechanisms by which GABAergic contribute sculpting circuits, how dysregulation may underlie emergence numerous neurodevelopmental neuropsychiatric disorders.

Language: Английский

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Reorganization of Brain Networks as a Substrate of Resilience: An Analysis of Cytochrome c Oxidase Activity in Rats

Neuroscience, Journal Year: 2023, Volume and Issue: 516, P. 75 - 90

Published: Feb. 16, 2023

The unpredictable chronic mild stress (UCMS) model has been used to induce depressive-like symptoms in animal models, showing adequate predictive validity. Our work aims evaluate the effects of environmental enrichment (EE) on resilience this experimental depression. We also aim assess changes brain connectivity using cytochrome c oxidase histochemistry cerebral regions related cognitive-affective processes associated with depressive disorder: dorsal hippocampus, prefrontal cortex, amygdala, accumbens, and habenula nuclei. Five groups rats were used: UCMS, EE, EE + UCMS (enrichment stress), BG (basal level activity), CONT (behavioral tests only). assessed hedonic responses elicited by sucrose solution a consumption test; anxiety was evaluated elevated zero maze test, unconditioned fear cat odor test. behavioral results showed that protocol induces anhedonia anxiety. But these are attenuated previous exposure EE. Regarding activity, group greater activity compared group. induced functional reorganization activity. different patterns connections between regions. favors could reduce vulnerability disorders such as depression anxiety, modifying metabolic

Language: Английский

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1-Methyltryptophan treatment ameliorates high-fat diet-induced depression in mice through reversing changes in perineuronal nets

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: May 30, 2024

Depression and obesity are prevalent disorders with significant public health implications. In this study, we used a high-fat diet (HFD)-induced obese mouse model to investigate the mechanism underlying HFD-induced depression-like behaviors. mice exhibited behaviors reduction in hippocampus volume, which were reversed by treatment an indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyltryptophan (1-MT). Interestingly, no changes IDO levels observed post-1-MT treatment, suggesting that other mechanisms may be involved anti-depressive effect of 1-MT. We further conducted RNA sequencing analysis clarify potential 1-MT depressive found enrichment shared differential genes extracellular matrix (ECM) organization pathway between 1-MT-treated untreated mice. Therefore, hypothesized ECM play crucial role To end, investigated perineuronal nets (PNNs), assemblies preferentially ensheath parvalbumin (PV)-positive interneurons many abnormalities. HFD is associated excessive accumulation PV-positive neurons upregulation PNNs, affecting synaptic transmission leading glutamate-gamma-aminobutyric acid imbalances hippocampus. The effectively these changes, highlighting PNN-related exerts its effect.

Language: Английский

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Hippocampal parvalbumin and perineuronal nets: Possible involvement in anxiety‐like behavior in rats

Hippocampus, Journal Year: 2023, Volume and Issue: 34(3), P. 156 - 165

Published: Dec. 15, 2023

Abstract The excitatory‐inhibitory imbalance has been considered an important mechanism underlying stress‐related psychiatric disorders. In the present study, rats were exposed to 6 days of inescapable foot shock (IFS) induce stress. open field test and elevated plus maze showed that IFS‐exposed exhibited increased anxiety‐like behavior. Immunofluorescence IFS had a decreased density GAD67‐immunoreactive interneurons in dorsal hippocampal CA1 region, while no significant change CaMKIIα‐immunoreactive glutamatergic neurons was seen. We investigated expression different interneuron subtype markers, including parvalbumin (PV), somatostatin (SST), calretinin (CR), noted marked decline PV‐immunoreactive region rats. perineuronal net (PNN) is specialized extracellular matrix structure primarily around PV interneurons. used Wisteria floribunda agglutinin lectin label PNNs observed proportion PNN‐coated PV‐positive CA1. number PSD95‐positive excitatory synaptic puncta on soma PNN‐free significantly higher than Our findings suggest effect GABAergic could be cell‐type‐specific. Loss phenotype may contribute anxiety dysregulated PV‐PNN relationship after traumatic stress exposure might represent one neurobiological correlates

Language: Английский

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Scoping review on environmental enrichment: Are critical periods and sex differences adequately studied?

Pharmacology Biochemistry and Behavior, Journal Year: 2022, Volume and Issue: 218, P. 173420 - 173420

Published: June 16, 2022

Language: Английский

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Early life adversity drives sex-dependent changes in 5-mC DNA methylation of parvalbumin cells in the prefrontal cortex in rats

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

Published: Feb. 1, 2024

Early life adversity (ELA) can result in increased risk for developing affective disorders, such as anxiety or depression, later life, with women showing risk. Interactions between an organism's genes and their environment play key roles producing, well mitigating, neuropathology. Our current understanding of the underlying epigenomic drivers ELA associated depression are limited, this stems part from complexity biochemical processes how early experiences shapes behavior. Epigenetic alterations, experience-driven modifications to DNA, be leveraged understand interplay environment. The present study characterized DNA methylation patterning, assessed via evaluation 5-methylcytosine (5-mC), following a Sprague Dawley rat model induced by caregiver deprivation. This utilized maternal separation investigate sex- age-specific outcomes on epigenetic patterning parvalbumin (PV)-containing interneurons prefrontal cortex (PFC), subpopulation inhibitory neurons which dysfunction. While global analysis 5-mC CpG site specific pyrosequencing PV promoter, Pvalb, showed no obvious effects ELA, when analyses were restricted assessing intensity colocalized cells, there significant sex age dependent effects. We found that leads sex-specific changes cell counts, counts predicted intensity, males females distinct patterns outcomes. also produced corticosterone reactivity, juvenile blunted stress hormone response compared controls. Overall, led developmental shift profile, is comparable profiles seen at timepoint, may mediated alterations driven altered methylation.

Language: Английский

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A TrkB cleavage fragment in hippocampus promotes Depressive-Like behavior in mice

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 119, P. 56 - 83

Published: March 29, 2024

Language: Английский

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