Low-Dose Ketamine Improved Brain Network Integrity Among Patients With Treatment-Resistant Depression and Suicidal Ideation

Psychiatry Research, Journal Year: 2025, Volume and Issue: unknown, P. 116377 - 116377

Published: Jan. 1, 2025

Language: Английский

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Maternal immune activation followed by peripubertal stress combinedly produce reactive microglia and confine cerebellar cognition

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 3, 2025

The functional alteration of microglia arises in brains exposed to external stress during early development. Pathophysiological findings neurodevelopmental disorders such as schizophrenia and autism spectrum disorder suggest cerebellar deficits. However, the link between stress-induced reactivity dysfunction is missing. Here, we investigate developmental immune environment translational mouse models that combine two risk factors: maternal infection repeated social defeat (2HIT). We find synergy inflammatory insults, leading microglial increase specifically cerebellum both sexes. Microglial turnover correlates with Purkinje neuron loss 2HIT mice. Highly multiplexed imaging-mass-cytometry identifies a cell transition TREM2(+) stress-associated cerebellum. Single-cell-proteomic clustering reveals IL-6- TGFβ-signaling association transitions. Reduced excitability remaining cells, cerebellum-involved brain-wide dysconnectivity, behavioral abnormalities indicate cognitive dysfunctions animals, which are ameliorated by systemic cerebellum-specific replacement. Early alters function, linked autism. In model, increased its turnover, causing dysfunction, was improved

Language: Английский

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Repurposing Ketamine in the Therapy of Depression and Depression-Related Disorders: Recent Advances and Future Potential

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2024

Depression represents a prevalent and enduring mental disorder of significant concern within the clinical domain. Extensive research indicates that depression is very complex, with many interconnected pathways involved. Most related to focuses on monoamines, neurotrophic factors, hypothalamic-pituitary-adrenal axis, tryptophan metabolism, energy mitochondrial function, gut-brain glial cell-mediated inflammation, myelination, homeostasis, brain neural networks. However, recently, Ketamine, an ionotropic N-methyl-D-aspartate (NMDA) receptor antagonist, has been discovered have rapid antidepressant effects in patients, leading novel successful treatment approaches for mood disorders. This review aims summarize latest findings insights into various signaling systems observed patients animal models, providing more comprehensive view neurobiology anxious-depressive-like behavior. Specifically, it highlights key mechanisms ketamine as rapid-acting antidepressant, aiming enhance neuropsychiatric Moreover, we discuss potential prophylactic or therapeutic intervention stress-related psychiatric

Language: Английский

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Identification of differentially expressed genes in the medial prefrontal cortex of rats subjected to chronic unpredictable mild stress and treated with electroacupuncture

Genomics, Journal Year: 2024, Volume and Issue: 116(5), P. 110901 - 110901

Published: July 22, 2024

Major depressive disorder is a chronic mental health condition that seriously impacts afflicted individuals. Although electroacupuncture has proven to be an effective therapy for depression, its underlying biological mechanism remains largely unknown. In this study, we aimed investigate the effects of on depression-like behavior and identify potential target genes related those effects. To achieve this, subjected rats unpredictable mild stress (CUMS) used sucrose preference, forced swimming, open-field tests determine their in absence or after receipt treatment. RNA sequencing technology was then reveal differentially expressed associated with depression treatment medial prefrontal cortex (mPFC). Repeated treatments at Baihui (GV20) Taichong (LR3) acupoints significantly alleviated behavioral defects animals. Genomic revealed several significant changes mPFC transcriptome received Through differential gene expression analysis, found reversed CUMS-induced downregulation 46 upregulation 13 genes. Among genes, Casr, Bdkrb2, Gnb3, Ccl1 were conclusion, verified antidepressant effect, involves multiple systems targets.

Language: Английский

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Maternal immune activation and peripubertal stress synergistically produce reactive microglia and confine cerebellar cognitive function.

Published: May 9, 2024

The functional alteration of microglia emerges in the brains exposed to extrinsic stress insults during early development. Pathophysiological findings psychiatric disorders such as schizophrenia and autism implied a localized deficit cerebellum. However, link between reactivity cerebellar dysfunction is missing. Here, we investigated developmental immune environment translational mouse models that combine two risk factors: maternal infection repeated social defeat (i.e., 2HIT). We found synergy inflammatory produced reactive microglia, specifically cerebellum both sexes. microglial proliferation correlated with Purkinje neuron loss 2HIT mice. Highly multiplexed imaging-mass-cytometry demonstrated TREM2-positive population stress-associated Single-cell-proteomic clustering revealed IL-6- TGFβ-signaling association cell transition. cells reduced excitability, cerebellum-involved brain-wide dysconnectivity, behavioral anomalies underpin cognitive dysfunctions animals, ameliorated by cerebellum-specific replacement.

Language: Английский

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Innovative Ketamine Formulations: Enhancing Therapeutic Efficacy and Safety

ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(8), P. 1188 - 1190

Published: July 25, 2024

Ketamine, originally developed as an anesthetic, has shown significant potential for treating depression, chronic pain, and other conditions. However, its conventional formulations often result in side effects such hallucinations dizziness due to rapid spikes blood concentration. This article explores recent patents that optimize ketamine delivery efficacy: subcutaneous injectable compositions, conjugates with various molecules, dual-release combining aspirin. These innovations promise improve ketamine-based treatments' pharmacokinetic profiles, therapeutic outcomes, safety.

Language: Английский

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Sex-differential markers of psychiatric risk and treatment response based on premature aging of functional brain network dynamics and peripheral physiology

Biological Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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