Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus

Journal of Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 154(4), P. 236 - 245

Published: Feb. 9, 2024

Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability link different signaling systems exert function the brain through chaperone actions, especially neuropsychiatric disorders. YL-0919, novel σ-1 agonist developed by our institute, shown antidepressive anxiolytic effects variety animal models, but on PPD have not been revealed. In present study, excitatory/inhibitory hippocampus was reflected GABA glutamate their associated excitatory-inhibitory proteins, HPA axis hormones were assessed ELISA. Finally, immunofluorescence for markers newborn neuron undertaken dentate gyri, along with dendritic spine staining arborization tracing. YL-0919 rapidly improves anxiety depressive-like behavior PPD-like mice within one week, normalizing excitation/inhibition as well activity. rescued decrease hippocampal complexity density induced estrogen withdrawal. study results suggest that elicits therapeutic effect mice; therefore, may be promising target treatment future.

Language: Английский

---

Involvement of brain-derived neurotrophic factor signaling in the pathogenesis of stress-related brain diseases

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Sept. 14, 2023

Neurotrophins including brain-derived neurotrophic factor, BDNF, have critical roles in neuronal differentiation, cell survival, and synaptic function the peripheral central nervous system. It is well known that a variety of intracellular signaling stimulated by TrkB, high-affinity receptor for involved physiological pathological aspects via affecting viability, function, neurogenesis, cognitive function. As expected, an alteration BDNF/TrkB system suspected to be one molecular mechanisms underlying decline diseases mental disorders. Recent evidence has also highlighted possible link between TrkB chronic stress. Furthermore, it been demonstrated downregulation stress role pathogenesis Alzheimer’s disease (AD) In this review, we introduce current showing close relationship development cognition impairment stress-related disorders, contribution upregulation therapeutic approach against these brain diseases.

Language: Английский

---

Suvorexant improves mitochondrial dynamics with the regulation of orexinergic and mTOR activation in rats exhibiting PTSD-like symptoms

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 350, P. 24 - 38

Published: Jan. 6, 2024

Language: Английский

---

An insight into crosstalk among multiple signalling pathways contributing to the pathophysiology of PTSD and depressive disorders

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2024, Volume and Issue: 131, P. 110943 - 110943

Published: Jan. 14, 2024

Language: Английский

---

Artemisinin reduces PTSD-like symptoms, improves synaptic plasticity, and inhibits apoptosis in rats subjected to single prolonged stress

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 6, 2024

Post-Traumatic Stress Disorder (PTSD) is a chronic mental disorder characterized by symptoms of panic and anxiety, depression, impaired cognitive functioning, difficulty in social interactions. While the effect traditional Chinese medicine artemisinin (AR) on PTSD unknown, its therapeutic benefits have been demonstrated studies models multiple neurological disorders. This study aimed to extend such findings investigating effects AR administration rat model induced regimen single prolonged stress (SPS). After rats were subjected SPS protocol, was administered impact PTSD-like behaviors evaluated. In present study, multitude behavioral tests evaluate related memory function, The expression hippocampal synaptic plasticity-related proteins detected using Western blot immunofluorescence. ultrastructure synapses observed under transmission electron microscopy. apoptosis neurons examined with blot, TUNEL staining, HE staining. results showed that alleviated phenotypes rats, including behavior indicative deficits, diminished sociability. further improve plasticity inhibit neuronal rats. These suggest administering after onset severe traumatic events may alleviate interaction, plasticity, diminish apoptosis. Hence, provides evidence for AR’s potential as multi-target agent treatment PTSD.

Language: Английский

---

Corticosterone-induced postpartum depression induces depression-like behavior and impairs hippocampal neurogenesis in adolescent offspring via HPA axis and BDNF-mTOR pathway

Neurobiology of Stress, Journal Year: 2025, Volume and Issue: 34, P. 100708 - 100708

Published: Jan. 1, 2025

Postpartum depression (PPD) adversely affects the growth and development of offspring, increasing risk various internalizing behaviorsduring adolescence. Studies have shown that corticosterone (CORT)-induced PPD neurogenesis in which is closely related to onset depression. However, underlying mechanisms these changes offspring mothers remain unexplored. In this study, we demonstrated postpartum mice treated with high CORT experienced activation hypothalamic-pituitary-adrenal (HPA) axis, induced depressive-like behavior impaired maternal caring behavior. Furthermore, adolescent exhibited depression-like behavior, learning memory deficits. These also showed diminished levels DCX+, decreased synaptic proteins, reduced dendritic spine density length hippocampus. Additionally, detected increased serum stressed hormones hippocampal glucocorticoid receptor (GR) protein level offspring. We found expression brain-derived neurotrophic factor (BDNF) phosphorylation tyrosine kinase B (TrkB), (AKT), mammalian target rapamycin (mTOR) proteins results indicated behavioral deficits neuronal damage observed may be HPA axis dysfunction inhibition BDNF-mTOR pathway. conclusion, our findings confirm induces impairs mice, turn their offspring's emotion cognitive This impact characterized by

Language: Английский

---

Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD

Psychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Abstract Rationale Existing studies predominantly focus on the molecular and neurobiological mechanisms underlying Ketamine’s acute treatment effects post-traumatic stress disorder (PTSD). This emphasis has largely overlooked its sustained therapeutic effects, which hold significant potential for development of targeted interventions. Objectives systematic review examines pharmacokinetic pharmacodynamic ketamine PTSD, differentiating between immediate effects. Method A comprehensive search across databases (Web Science, Scopus, Global Health, PubMed) grey literature yielded 317 articles, where 29 met inclusion criteria. These included preclinical models clinical trials, through neurotransmitter regulation, gene expression, synaptic plasticity, neural pathways (PROSPERO ID: CRD42024582874). Results We found accumulating evidence that ketamine, involve changes in GABA, glutamate, glutamine levels, trigger re-regulation BDNF, enhancing plasticity via such as TrkB PSD-95. Other influences also include c-Fos, GSK-3, HDAC, HCN1, modulation hormones like CHR ACTH, alongside immune responses (IL-6, IL-1β, TNF-α). Sustained arise from remodulations prolonged expression. mTOR-mediated BDNF alterations GSK-3β, FkBP5, GFAP, ERK phosphorylation, epigenetic modifications (DNMT3, MeCP2, H3K27me3, mir-132, mir-206, HDAC). Conclusion promote long-term stability key brain regions, contributing to benefits. Understanding behind ketamine’s is critical developing safe effective personalised treatments, potentially leading more recovery.

Language: Английский

---

Psychedelic Drugs in Mental Disorders: Current Clinical Scope and Deep Learning‐Based Advanced Perspectives

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Mental disorders are a representative type of brain disorder, including anxiety, major depressive depression (MDD), and autism spectrum disorder (ASD), that caused by multiple etiologies, genetic heterogeneity, epigenetic dysregulation, aberrant morphological biochemical conditions. Psychedelic drugs such as psilocybin lysergic acid diethylamide (LSD) have been renewed fascinating treatment options gradually demonstrated potential therapeutic effects in mental disorders. However, the multifaceted conditions psychiatric resulting from individuality, complex interplay, intricate neural circuits impact systemic pharmacology psychedelics, which disturbs integration mechanisms may result dissimilar medicinal efficiency. The precise prescription psychedelic remains unclear, advanced approaches needed to optimize drug development. Here, recent studies demonstrating diverse pharmacological psychedelics reviewed, emerging perspectives on structural function, microbiota-gut-brain axis, transcriptome discussed. Moreover, applicability deep learning is highlighted for development basis big data. These provide insight into interindividual factors enhance discovery precision medicine.

Language: Английский

---

(2 R, 6 R)-hydroxynorketamine ameliorates PTSD-like behaviors during the reconsolidation phase of fear memory in rats by modulating the VGF/BDNF/GluA1 signaling pathway in the hippocampus

Behavioural Brain Research, Journal Year: 2024, Volume and Issue: 476, P. 115273 - 115273

Published: Sept. 24, 2024

Language: Английский

---

(2R,6R)-hydroxynorketamine alleviates PTSD-like endophenotypes by regulating the PI3K/AKT signaling pathway in rats

Pharmacology Biochemistry and Behavior, Journal Year: 2024, Volume and Issue: unknown, P. 173891 - 173891

Published: Oct. 1, 2024

Language: Английский

---