The neurobiological mechanisms and therapeutic prospect of extracellular ATP in depression

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(2)

Published: Feb. 1, 2024

Depression is a prevalent psychiatric disorder with high long-term morbidities, recurrences, and mortalities. Despite extensive research efforts spanning decades, the cellular molecular mechanisms of depression remain largely unknown. What's more, about one third patients do not have effective anti-depressant therapies, so there an urgent need to uncover more guide development novel therapeutic strategies. Adenosine triphosphate (ATP) plays important role in maintaining ion gradients essential for neuronal activities, as well transport release neurotransmitters. Additionally, ATP could also participate signaling pathways following activation postsynaptic receptors. By searching website PubMed articles "ATP depression" especially focusing on extracellular (eATP) last 5 years, we found that numerous studies implied insufficient from astrocytes lead exogenous supply eATP or endogenously stimulating alleviate depression, highlighting potential alleviating depression.

Language: Английский

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Neuroimmune mechanisms in autism etiology - untangling a complex problem using human cellular models

Oxford Open Neuroscience, Journal Year: 2024, Volume and Issue: 3

Published: Jan. 1, 2024

Autism spectrum disorder (ASD) affects 1 in 36 people and is more often diagnosed males than females. Core features of ASD are impaired social interactions, repetitive behaviors deficits verbal communication. a highly heterogeneous heritable disorder, yet its underlying genetic causes account only for up to 80% the cases. Hence, subset cases could be influenced by environmental risk factors. Maternal immune activation (MIA) response inflammation during pregnancy, which can lead increased inflammatory signals fetus. Inflammatory cross placenta blood brain barriers affecting fetal development. Epidemiological animal studies suggest that MIA contribute etiology. However, human mechanistic have been hindered lack experimental systems replicate impact Therefore, mechanisms altered pre-natal development, underlie pathogenesis largely understudied. The advent cellular models with induced pluripotent stem cell (iPSC) organoid technology closing this gap knowledge providing both access molecular manipulations culturing capability tissue would otherwise inaccessible. We present an overview multiple levels evidence from clinical, epidemiological, provide potential link between higher inflammation. More importantly, we discuss how cell-derived may constitute ideal system mechanistically interrogate effect early stages

Language: Английский

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Astrocytic IP3Rs: Beyond IP3R2

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: July 30, 2021

Astrocytes are sensitive to ongoing neuronal/network activities and, accordingly, regulate neuronal functions (synaptic transmission, synaptic plasticity, behavior, etc.) by the context-dependent release of several gliotransmitters (e.g., glutamate, glycine, D -serine, ATP). To sense diverse input, astrocytes express a plethora G-protein coupled receptors, which couple, via G i/o and q , intracellular Ca 2+ channel IP 3 -receptor (IP R). Indeed, manipulating astrocytic R-Ca signaling is highly consequential at network behavioral level: Depleting R subtype 2 R2) results in reduced GPCR-Ca impaired plasticity; enhancing affects cognitive such as learning memory, sleep, mood. However, result discrepancies literature, role GPCR-IP signaling, especially under physiological conditions, remains inconclusive. One primary reason for this could be that R2 has been used represent all Rs, including R1 R3. R3 unique channels their own right; they have biophysical properties, often display distinct distribution, differentially regulated. As result, mediate different roles R2. Thus, these additional promise enrich diversity spatiotemporal dynamics provide opportunities integrating input modulating astrocyte–neuron communication. The current review weighs evidence supporting existence multiple astrocytic-IP isoforms, summarizes sub-type specific properties shape dynamics. We also discuss existing experimental tools future refinements better recapitulate endogenous each isoform.

Language: Английский

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Insights into the role of intracellular calcium signaling in the neurobiology of neurodevelopmental disorders

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

Published: Feb. 15, 2023

Calcium (Ca 2+ ) comprises a critical ionic second messenger in the central nervous system that is under control of wide array regulatory mechanisms, including organellar Ca stores, membrane channels and pumps, intracellular -binding proteins. Not surprisingly, disturbances homeostasis have been linked to neurodegenerative disorders, such as Alzheimer’s Parkinson’s diseases. However, aberrations also implicated neuropsychiatric disorders with strong neurodevelopmental component autism spectrum disorder (ASD) attention-deficit hyperactivity (ADHD) schizophrenia (SCZ). While plasma synaptic proteins extensively studied, increasing evidence suggests prominent role for endoplasmic reticulum (ER), aberrant neurodevelopment. In context current mini-review, we discuss recent findings implicating -handling regulators sarco-ER ATPase 2 (SERCA2), ryanodine receptors (RyRs), inositol triphosphate (IP 3 Rs), parvalbumin (PVALB), emergence ASD, SCZ, ADHD.

Language: Английский

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Spontaneous and multifaceted ATP release from astrocytes at the scale of hundreds of synapses

Glia, Journal Year: 2023, Volume and Issue: 71(9), P. 2250 - 2265

Published: June 1, 2023

Abstract Astrocytes participate in information processing by releasing neuroactive substances termed gliotransmitters, including ATP. Individual astrocytes come into contact with thousands of synapses their ramified structure, but the spatiotemporal dynamics ATP gliotransmission remains unclear, especially physiological brain tissue. Using a genetically encoded fluorescent sensor, GRAB ATP1.0 , we discovered that extracellular increased locally and transiently absence stimuli neuron–glia co‐cultures, cortical slices, anesthetized mouse brain. Spontaneous release events were tetrodotoxin‐insensitive suppressed gliotoxin, fluorocitrate, typically spread over 50–250 μm 2 area at concentrations capable activating purinergic receptors. Besides, most did not coincide Ca 2+ transients, intracellular buffering BAPTA‐AM affect event frequency. Clustering analysis revealed these followed multiple distinct kinetics, blockade exocytosis only decreased minor group slow events. Overall, spontaneously through mechanisms, mainly non‐vesicular ‐independent manners, thus potentially regulating hundreds all together.

Language: Английский

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