Immunity, Journal Year: 2023, Volume and Issue: 56(9), P. 1983 - 1985
Published: Sept. 1, 2023
Language: Английский
Revista Brasileira de Enfermagem, Journal Year: 2025, Volume and Issue: 78(suppl 2)
Published: Jan. 1, 2025
RESUMO Objetivos: identificar a ocorrência de experiências adversas na infância entre crianças alto risco ao nascer. Métodos: rstudo quantitativo, transversal e descritivo, realizado em um Consórcio Intermunicipal Saúde no Paraná, setembro 2022 fevereiro 2023, com 45 cuidadores risco. A coleta dados ocorreu domicílio, utilizando três questionários. Os resultados foram analisados forma descritiva, base teoria da árvore dos eventos adversos infância. Resultados: prevalência foi 18,6%. Em relação aos tipos eventos, 64,3% relataram violência; 28% divórcio; 22,2% abuso substâncias; 73,3% apresentaram dificuldade para adquirir produtos básicos; 62,2% estavam situação desemprego e/ou baixa renda; 55,6% residiam áreas conflito; 44,4% não tinham acesso esgoto. Conclusões: os são multicausais intersetoriais, representando ameaças desenvolvimento infantil. Agenda 2030 propõe dimensões o enfrentamento dessa problemática, investir
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0
Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16
Published: March 20, 2025
The body instinctively responds to external stimuli by increasing energy metabolism and initiating immune responses upon receiving stress signals. Corticosterone (CORT), a glucocorticoid (GC) that regulates secretion along the hypothalamic-pituitary-adrenal (HPA) axis, mediates neurotransmission humoral regulation. Due widespread expression of receptors (GR), effects CORT are almost ubiquitous in various tissue cells. Therefore, on one hand, is molecular signal activates body’s system during other due chemical properties GCs, anti-inflammatory act as stabilizers control response stress. Inflammation manifestation activation. plays dual roles this process both promoting inflammation exerting As hormone, levels fluctuate with degree duration stress, determining its changes it induces. essential for resist diseases maintain homeostasis, imbalance being key factor development diseases. understanding role mechanisms action immunity crucial. This review addresses important issue summarizes interactions between system.
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2888 - 2888
Published: March 22, 2025
Alzheimer's disease (AD) pathogenesis involves progressive synaptic degeneration, a process potentially driven by maladaptive microglial pruning activity. While loss is hallmark of AD, the molecular signals triggering pathological microglia-mediated engulfment remain elusive. Clec7a-a key marker disease-associated microglia (DAM)-is known to activate spleen tyrosine kinase (SYK) signaling, enhancing Aβ phagocytosis and neuroprotective functions in 5×FAD models. However, its role regulating synapse-microglia interactions under tauopathic conditions remains undefined. Our analysis revealed activation Clec7a-SYK signaling axis hippocampus PS19 tauopathy mice, correlating with progression. Spatial mapping demonstrated significant co-localization Clec7a hippocampal microglia, suggesting cell-autonomous signaling. The pharmacological inhibition achieved multimodal therapeutic effects attenuating hyperreactivity, suppressing neuroinflammatory cytokine release, restoring physiological turnover. Mechanistically, we identified MD2 as "eat-me" signal on tauopathy-related synapses, recruiting Clec7a+ drive aberrant elimination mice. Strikingly, blockade rescued hippocampal-dependent memory deficits behavioral tests. These findings position context-dependent target, strategies showing particular promise for degeneration.
Language: Английский
Citations
0
Published: March 13, 2024
In the brain, astrocytes regulate shape and functions of synaptic vascular compartments through a variety released factors membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to onset severe pathologies. Clinical pre-clinical studies show alterations in cell number, morphology, molecular makeup astrocyte-dependent processes different affected regions neurodevelopmental (ND) neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate mature during critical period early postnatal time window elevated glia-dependent regulation proper balance between synapse formation/elimination, which is pivotal refining connectivity. Therefore, any intrinsic and/or extrinsic altering these may result an aberrant remodelling mental The peculiar bridging position further allows them “compute” state consequently secrete bloodstream, serve as diagnostic biomarkers distinct healthy or disease conditions.Here, we collect recent advancements regarding astrogenesis astrocyte-mediated neuronal network periods focusing elimination. We then propose alternative hypotheses for involvement aberrancies ND NP light well-known differential prevalence certain disorders males females, also discuss putative sex-dependent influences events.From translational perspective, understanding age- astrocyte-specific functional changes help identify cellular (dys)functions health disease, favouring development tools selection tailored treatment options male/female patients.
Language: Английский
Citations
3
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
Citations
3
Advanced Science, Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 12, 2024
Abstract Lysosomes are important cellular structures for human health as centers recycling, signaling, metabolism and stress adaptation. However, the potential role of lysosomes in stress‐related emotions has long been overlooked. Here, it is found that lysosomal morphology astrocytes altered medial prefrontal cortex (mPFC) susceptible mice after chronic social defeat stress. A screen lysosome‐related genes revealed expression mucolipin 1 gene ( Mcoln1 ; protein: TRP channel 1) decreased depressed patients. Astrocyte‐specific knockout (TRPML1) induced depressive‐like behaviors by inhibiting exocytosis‐mediated adenosine 5′‐triphosphate (ATP) release. Furthermore, this response astrocytic mediated transcription factor EB (TFEB), overexpression TRPML1 rescued astrocyte‐specific TFEB. Collectively, these findings reveal a stress‐sensing signaling pathway contributing to development depression identify lysosome target organelle antidepressants.
Language: Английский
Citations
3
Frontiers in Bioscience-Landmark, Journal Year: 2023, Volume and Issue: 28(12), P. 355 - 355
Published: Dec. 28, 2023
Alzheimer's disease is widely regarded as poorly treated due to poor conceptualization. For 40 years, pathophysiology has focused on two culprits, amyloid-β induced plaques and hyperphosphorylated tau associated tangles, with no significant treatment advance. This confounded by data showing be an endogenous antimicrobial that increased in a wide array of diverse medical conditions heightened inflammation. article reviews the wider bodies pertaining pathophysiology, highlighting role suppressed astrocyte mitochondrial function melatonergic pathway core hub driving neuronal loss dementia. It proposed over aging becomes dysregulated, at least partly mediated systemic processes involving 10-fold decrease pineal melatonin leading attenuated capacity night-time dampen residual daytime Suppressed also attenuates melatonin's inhibition glucocorticoid receptor nuclear translocation, thereby changing not only stress/hypothalamus-pituitary-adrenal (HPA) axis consequences but cortisol awakening response, which 'primes body for coming day'. Gut microbiome-derived butyrate inhibits well inducing pathway. prevents autocrine paracrine effects limiting levels effects. production induction lactate, decreasing metabolism The lactate melatonin, coupled suppression decreases mitophagy, major histocompatibility complex (MHC)-1. MHC-1 initiates chemoattraction CD8+ t cells, destruction being driven 'autoimmune'/'immune-mediated' processes. may therefore conceptualized initiated act astrocytes hub, leaving neurons deplete appropriate metabolic substrates co-ordinated antioxidants. culminates 'immune-mediated' cell death. Future research treatment/prevention implications are indicated.
Language: Английский
Citations
7
Frontiers in Ophthalmology, Journal Year: 2024, Volume and Issue: 3
Published: Jan. 8, 2024
Glial cells, a type of non-neuronal cell found in the central nervous system (CNS), play critical role maintaining homeostasis and regulating CNS functions. Recent advancements technology have paved way for new therapeutic strategies fight against glaucoma. While intraocular pressure (IOP) is most well-known modifiable risk factor, significant number glaucoma patients normal IOP levels. Because complex, multifactorial disease influenced by various factors that contribute to its onset progression, it imperative we consider beyond effectively prevent or slow down disease’s advancement. In realm neurodegenerative diseases, glial cells emerged as key players due their pivotal roles initiating hastening progression. The inhibition dysregulated function holds potential protect neurons restore brain function. Consequently, represent an enticing candidate glaucoma, even though majority research has historically concentrated solely on retinal ganglion (RGCs). addition neuroprotection RGCs, proper regulation can also facilitate structural functional recovery retina. this review, offer overview recent understanding non-cell-autonomous mechanisms underlying pathogenesis Furthermore, state-of-the-art technologies opened up possibilities regenerating optic nerve, which was previously believed be incapable regeneration. We will delve into regeneration nerve restoration visual
Language: Английский
Citations
2
Advanced Science, Journal Year: 2024, Volume and Issue: 11(31)
Published: June 17, 2024
Extracellular matrix (ECM) remodeling is strongly linked to Alzheimer's disease (AD) risk; however, the underlying mechanisms are not fully understood. Here, it found that injection of chondroitinase ABC (ChABC), mimicking ECM remodeling, into medial prefrontal cortex (mPFC) reversed short-term memory loss and reduced amyloid-beta (Aβ) deposition in 5xFAD mice. also reactivated astrocytes, levels aggrecan Aβ plaques, enhanced astrocyte recruitment surrounding plaques. Importantly, autophagy-lysosome pathway thereby mediating clearance alleviating AD pathology. promoted plaque phagocytosis by astrocytes activating astrocytic receptor MERTK promoting vesicle circulation. The study identified a cellular mechanism which activates autophagy-lysosomal alleviates Targeting may represent potential therapeutic strategy for serve as reference treatment this disease.
Language: Английский
Citations
2
Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(8), P. 2264 - 2278
Published: July 29, 2024
Alzheimer’s disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence curative treatments. The current therapeutic strategies, primarily based on cholinesterase inhibitors N-methyl-D-aspartate receptor antagonists, offer limited symptomatic relief without halting progression, highlighting an urgent need for novel research directions that address key mechanisms underlying disease. Recent studies have provided insights into critical role glycolysis, fundamental energy metabolism pathway in brain, pathogenesis Alterations glycolytic processes within neurons glial cells, including microglia, astrocytes, oligodendrocytes, been identified as contributors pathological landscape Glycolytic changes impact neuronal function, thus offering promising targets intervention. purpose this review is consolidate knowledge modifications glycolysis associated with explore by which these abnormalities contribute onset progression. Comprehensive focus pathways through dysfunction influences pathology should provide potential strategies pave way groundbreaking treatments, emphasizing importance understanding metabolic quest clarification management
Language: Английский
Citations
2