Role of Glial Cells in Depression and Drug Addiction DOI Open Access
Yousef Tizabi, Bruk Getachew, Sheketha R. Hauser

et al.

Published: May 3, 2024

Major depressive disorder (MDD) and substance use (SUD) are of immense medical social concerns. Although significant progress on neuronal involvement in mood reward circuitries has been achieved, only relatively recently the role glia these disorders have attracted attention. Detail understanding glial function devastating diseases could offer novel interventions. Here, following a brief review involved regulation perception, specific contribution neurotrophic factors, neuroinflammation gut microbiota to highlighted. In this context, cells (e.g., microglia, astroglia, oligodendrocytes synantocytes) phenotypic manifestation MDD or SUD emphasized. addition, potential knowledge developing therapeutics is touched upon.

Language: Английский

PI3K/AKT signaling pathway: Molecular mechanisms and therapeutic potential in depression DOI Creative Commons
Ningning Guo, Xin Wang,

Muran Xu

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107300 - 107300

Published: July 9, 2024

Depression is a serious global mental disorder. Numerous studies have found that depression may be closely related to decreased neurogenesis, neuroinflammation, neurotransmitter imbalance, and synaptic plasticity dysfunction. The pathogenesis of complex involves multiple signal transduction pathways molecular changes. PI3K/AKT pathway an essential signaling in neurons, which widely expressed emotion-related regions the brain. Therefore, play moderating role mood disorders. However, mechanism not been fully described. This review systematically summarized discussed its potential treatment depression. will help development antidepressants.

Language: Английский

Citations

32
The (neuro)inflammatory system in anxiety disorders and PTSD: Potential treatment targets DOI Creative Commons
Anupam Sah, Nicolas Singewald

Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown, P. 108825 - 108825

Published: Feb. 1, 2025

Language: Английский

Citations

2
Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction DOI Creative Commons
Yousef Tizabi, Bruk Getachew, Sheketha R. Hauser

et al.

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(6), P. 558 - 558

Published: May 30, 2024

Mood disorders and substance use disorder (SUD) are of immense medical social concern. Although significant progress on neuronal involvement in mood reward circuitries has been achieved, it is only relatively recently that the role glia these attracted attention. Detailed understanding glial functions devastating diseases could offer novel interventions. Here, following a brief review involved regulation perception, specific contributions neurotrophic factors, neuroinflammation, gut microbiota to highlighted. In this context, cells (e.g., microglia, astroglia, oligodendrocytes, synantocytes) phenotypic manifestation or SUD emphasized. addition, knowledge potential development therapeutics touched upon.

Language: Английский

Citations

13
SMOC2 promotes microglia activity and neuroinflammation in Alzheimer's disease DOI Creative Commons

Tianchi Wan,

Chunkai Wang

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Background Alzheimer's disease (AD), the leading cause of dementia, is characterized by cognitive decline and accumulation amyloid-β (Aβ). It affects millions, with numbers expected to double 2050. SMOC2, implicated in inflammation fibrosis, may play a role AD pathogenesis, particularly microglial cell function, offering potential therapeutic target. Objective (AD) leads neurodegeneration, affecting cognition, language, personality, underscoring urgency for effective treatments. Our study investigates secreted modular calcium-binding protein 2 (SMOC2) cells its impact on pathology. Methods We introduced SMOC2 overexpression interference vectors into treated Aβ. Activity phagocytosis were assessed using CCK8 flow cytometry. mRNA levels quantified qPCR, TGF-β1, p-NF-κB/NF-κB analyzed western blot. Aβ content was determined ELISA, immunofluorescence detected TNF-α, IL-1β, CD163, CD206. Results treatment inhibited activity phagocytosis, but disruption enhanced these functions (p < 0.05). increased expression levels, while reduced them 0.001). also decreased CD206, p-NF-κB/NF-κB, IL-1β Conclusions plays crucial activity, polarization, potentially through TGF-β1/NF-κB pathway, insights pathogenesis.

Language: Английский

Citations

1
Trends in research on novel antidepressant treatments DOI Creative Commons
Agnieszka Zelek-Molik, Ewa Litwa

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 27, 2025

Mood disorders, such as major depressive disorder and bipolar disorder, are among the most common mental illnesses a leading cause of disability worldwide. Key symptoms these conditions include depressed mood or anhedonia, sleep psychomotor disturbances, changes in appetite weight, fatigue loss energy. Prolonged cognitive disturbances further impair ability to think concentrate often accompanied by persistent feelings worthlessness excessive guilt. Collectively, underscore depression serious, long-term global health issue. In addition, clinical studies indicate growing number patients experiencing difficulties responding treatment, even long term. This phenomenon poses significant challenges for healthcare professionals, families, alike. As result, there is an urgent need therapies that both rapid-acting safe. review aims summarize prevailing trends research on novel antidepressants, emphasizing their diversity multi-directional mechanisms action. The development drugs increasingly focused achieving high efficacy, particularly treatment-resistant depression. Such advances offer potential rapid therapeutic effects without prolonged tedious administration older generation antidepressants. Findings from using animal models continue play crucial role predicting designing new strategies. These remain indispensable understanding physiological newly developed compounds, thereby guiding creation innovative treatments.

Language: Английский

Citations

1
Single-cell sequencing reveals an important role of SPP1 and microglial activation in age-related macular degeneration DOI Creative Commons
Shizhen Lei, Mang Hu,

Zhongtao Wei

et al.

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

Published: Jan. 8, 2024

Purpose To investigate the role of senescence-related cytokines (SRCs) in pathophysiology age-related macular degeneration (AMD). Design The whole study is based on single-cell and bulk tissue transcriptomic analysis human neuroretinas with or without AMD. data was obtained from Gene-Expression Omnibus (GEO) database. Methods For analysis, gene expression matrix goes through quality control (QC) filtering, being normalized, scaled integrated for downstream analysis. further analyses were performed using Seurat R package CellChat package. After cell type annotation, phenotype functional markers microglia investigated cell-cell communication performed. GSE29801 dataset contains neuroretina ( n = 118) group AMD patients. SPP1 subtypes compared by Student’s t -test. In addition, classified into SPP1-low SPP1-high groups according to level SPP1. differentially expressed genes between these two subsequently identified pathway enrichment conducted. Results Secreted phosphoprotein 1, as an SRC, revealed be highly SPP1-receptor signaling activated neuroretina. associated pro-inflammatory phagocytic state microglia. elevated late dry wet inflammatory pathways found Conclusion Our findings indicated that microglial activation might play important Therefore, serve a potential therapeutic target More vitro vivo studies are required confirm results effect SPP1-targeting strategy.

Language: Английский

Citations

6
Potential antidepressant effects of Traditional Chinese botanical drug formula Chaihu-Shugan-San and its active ingredients DOI Creative Commons
Ziyi Guo,

Tianjian Long,

Jianping Yao

et al.

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

Published: April 2, 2024

Background: Depression is a severe mental disorder that poses significant threat to both the physical and wellbeing of individuals. Currently, there are various methods for treating depression, including traditional Chinese herbal formulations like Chaihu-Shugan-San (CSS), which have shown effective antidepressant effects in clinical animal research. Objective: This review aims provide comprehensive synthesis evidence related CSS, considering preclinical studies, uncover its potential multi-level, multi-pathway, multi-target mechanisms depression identify active ingredients. Methods: A thorough search was conducted electronic databases, PubMed, MEDLINE, Web Science, Google Scholar, CNKI, Wanfang, using keywords such as “Chaihu Shugan” “depression” retrieve relevant literature on CSS The process adhered PRISMA guidelines. Results: consolidates underlying It emphasizes involvement regulation monoaminergic neurotransmitter systems, synaptic plasticity, hypothalamic-pituitary-adrenal axis, among other aspects. Conclusion: exerts pivotal role through pathways, system, inflammation, brain-derived neurotrophic factor levels, brain-gut axis. facilitates understanding current state research, fostering an in-depth exploration etiological discovery novel drugs.

Language: Английский

Citations

5
Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases DOI Creative Commons

Zarah R. Haniff,

Mariia Bocharova, Tim Mantingh

et al.

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 258, P. 108641 - 108641

Published: April 6, 2024

Major depression is an established risk factor for subsequent dementia, and in late life may also represent a prodromal state of dementia. Considering current challenges the clinical development disease modifying therapies focus research shifting towards prevention modification factors to alter neurodegenerative trajectory. Understanding mechanistic commonalities underlying affective symptoms cognitive decline reveal biomarkers aid early identification those at progressing dementia during preclinical phase disease, thus allowing timely intervention. Adult hippocampal neurogenesis (AHN) phenomenon that describes birth new neurons dentate gyrus throughout it associated with spatial learning, memory mood regulation. Microglia are innate immune system macrophages central nervous carefully regulate AHN via multiple mechanisms. Disruption both major microgliosis hallmark several diseases. Emerging evidence suggests psychedelics promote neuroplasticity, including neurogenesis, be immunomodulatory. In this context, psilocybin, serotonergic agonist rapid-acting antidepressant properties has potential ameliorate intersecting pathophysiological processes relevant narrative review, we on base effects psilocybin adult microglial form function; which suggest modulate mechanisms action, have implications altering progression from risk.

Language: Английский

Citations

5
Sex and Region-Specific Differences in Microglial Morphology and Function Across Development DOI Creative Commons
Indra R. Bishnoi, Evan A. Bordt

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

Citations

0
Schaftoside Reduces Depression- and Anxiogenic-like Behaviors in Mice Depression Models DOI Creative Commons

Hu Yue,

Yaoxue Gan,

Lei Jia

et al.

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(3), P. 238 - 238

Published: Feb. 24, 2025

Background: Major depressive disorder is a common mental health issue characterized by persistently low mood and high morbidity mortality. The major pathophysiology neuroinflammation, as evidenced elevated cytokine levels. Patients often fail to achieve full remission with the use of currently available antidepressants, prompting search for new treatment options. Schaftoside (SS), flavonoid found in traditional Chinese herbs, has both antioxidant anti-inflammatory properties. However, its antidepressant effects are poorly understood. Methods: Male C57BL/6 mice underwent chronic unpredictable mild stress (CUMS) lipopolysaccharide (LPS) induce depression- anxiety-like behaviors. SS was administered at 40, 80, 160 mg/kg 28 days. effect on depression-like behaviors assessed using behavioral assays, ELISA used measure pro-inflammatory cytokines serum hippocampus. Results: significantly decreased immobility forced swim tail suspension tests, increased sucrose preference test, reduced feeding latency novelty-suppressed test. These findings indicate improved depression showed that lowered interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-alpha levels hippocampus CUMS mice. Conclusions: Our study indicates anxiolytic effects, possibly through neuroinflammatory processes, making it promising therapeutic candidate depression, thus deserves further investigation into mechanisms clinical efficacy.

Language: Английский

Citations

0