Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5487 - 5487

Опубликована: Март 13, 2023

Autism spectrum disorder (ASD) is a neurodevelopmental (NDD) characterized by impairments in social communication, repetitive behaviors, restricted interests, and hyperesthesia/hypesthesia caused genetic and/or environmental factors. In recent years, inflammation oxidative stress have been implicated the pathogenesis of ASD. this review, we discuss pathophysiology ASD, particularly focusing on maternal immune activation (MIA). MIA one common risk factors for onset ASD during pregnancy. It induces an reaction pregnant mother’s body, resulting further placenta fetal brain. These negative cause developing brain subsequently behavioral symptoms offspring. addition, also effects anti-inflammatory drugs antioxidants basic studies animals clinical Our review provides latest findings new insights into involvements

Язык: Английский

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Astrocytes and brain-derived neurotrophic factor (BDNF)

Neuroscience Research, Год журнала: 2023, Номер 197, С. 42 - 51

Опубликована: Фев. 11, 2023

Astrocytes are emerging in the neuroscience field as crucial modulators of brain functions, from molecular control synaptic plasticity to orchestrating brain-wide circuit activity for cognitive processes. The cellular pathways through which astrocytes modulate neuronal and quite diverse. In this review, we focus on neurotrophic pathways, mostly those mediated by brain-derived factor (BDNF). Neurotrophins a well-known family trophic factors with pleiotropic functions survival, maturation activity. Within brain, BDNF is most abundantly expressed studied all neurotrophins. While have detailed knowledge effect neurons, much less known about its physiology astroglia. However, over last years new findings emerged demonstrating that take an active part into physiology. work, discuss state-of-the-art BDNF. Indeed, sense extracellular specific TrkB receptors activate intracellular responses greatly vary depending area, stage development expressed. also uptake recycle / proBDNF at synapses contributing plasticity. Finally, experimental evidence now available describing deficits astrocytic several neuropathologies, suggesting may represent promising target clinical translation.

Язык: Английский

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Activity-dependent compartmentalization of dendritic mitochondria morphology through local regulation of fusion-fission balance in neurons in vivo

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 8, 2024

Abstract Neuronal mitochondria play important roles beyond ATP generation, including Ca 2+ uptake, and therefore have instructive in synaptic function neuronal response properties. Mitochondrial morphology differs significantly between the axon dendrites of a given subtype, but CA1 pyramidal neurons (PNs) hippocampus, within dendritic arbor also display remarkable degree subcellular, layer-specific compartmentalization. In these neurons, ranges from highly fused elongated apical tuft, to more fragmented oblique basal compartments, thus occupy smaller fraction volume than tuft. However, molecular mechanisms underlying this striking subcellular compartmentalization are unknown, precluding assessment its impact on function. Here, we demonstrate that compartment-specific requires activity-dependent, Camkk2-dependent activation AMPK ability phosphorylate two direct effectors: pro-fission Drp1 receptor Mff recently identified anti-fusion, Opa1-inhibiting protein, Mtfr1l. Our study uncovers signaling pathway mitochondrial vivo through spatially precise activity-dependent regulation fission/fusion balance.

Язык: Английский

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Emerging evidence for astrocyte dysfunction in schizophrenia

Glia, Год журнала: 2022, Номер 70(9), С. 1585 - 1604

Опубликована: Май 30, 2022

Schizophrenia is a complex, chronic mental health disorder whose heterogeneous genetic and neurobiological background influences early brain development, precise etiology still poorly understood. not characterized by gross pathology, but involves subtle pathological changes in neuronal populations glial cells. Among the latter, astrocytes critically contribute to regulation of neurodevelopmental processes, any dysfunctions their morphological functional maturation may lead aberrant processes involved pathogenesis schizophrenia, such as mitochondrial biogenesis, synaptogenesis, glutamatergic dopaminergic transmission. Studies mechanisms regulating astrocyte therefore improve our understanding cellular molecular underlying schizophrenia.

Язык: Английский

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Foundations and implications of astrocyte heterogeneity during brain development and disease

Trends in Neurosciences, Год журнала: 2022, Номер 45(9), С. 692 - 703

Опубликована: Июль 23, 2022

Язык: Английский

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Nano‐Brake Halts Mitochondrial Dysfunction Cascade to Alleviate Neuropathology and Rescue Alzheimer's Cognitive Deficits

Advanced Science, Год журнала: 2023, Номер 10(7)

Опубликована: Янв. 26, 2023

Abstract Mitochondrial dysfunction has been recognized as the key pathogenesis of most neurodegenerative diseases including Alzheimer's disease (AD). The dysregulation mitochondrial calcium ion (Ca 2+ ) homeostasis and permeability transition pore (mPTP), is a critical upstream signaling pathway that contributes to cascade in AD pathogenesis. Herein, “two‐hit braking” therapeutic strategy synergistically halt Ca overload mPTP opening put on brake proposed. To achieve this goal, magnesium (Mg ), natural antagonist, siRNA central regulator cyclophilin D (CypD), are co‐encapsulated into designed nano‐brake; A matrix metalloproteinase 9 (MMP9) activatable cell‐penetrating peptide (MAP) anchored surface nano‐brake overcome blood‐brain barrier (BBB) realize targeted delivery cells brain. Nano‐brake treatment efficiently halts cerebrovascular endothelial cells, neurons, microglia powerfully alleviates neuropathology rescues cognitive deficits. These findings collectively demonstrate potential advanced design nanotherapeutics pathways provide powerful for modifying therapy.

Язык: Английский

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Metabolic perspective of astrocyte dysfunction in Alzheimer's disease and type 2 diabetes brains

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 158, С. 114206 - 114206

Опубликована: Янв. 5, 2023

The term type III diabetes (T3DM) has been proposed for Alzheimer's disease (AD) due to the shared molecular and cellular features between 2 (T2DM) insulin resistance-associated memory deficits cognitive decline in elderly individuals. Astrocytes elicit neuroprotective or deleterious effects AD progression severity. Patients with T2DM are at a high risk of impairment, targeting astrocytes might be promising alleviating neurodegeneration diabetic brain. Recent studies focusing on cell-specific activities brain have revealed important role metabolism (e.g., glucose metabolism, lipid metabolism), neurovascular coupling, synapses, synaptic plasticity. In this review, we discuss how their dysfunction result multiple pathological clinical from metabolic perspective potential comorbid mechanism these two diseases astrocytes.

Язык: Английский

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Astrocytic modulation of neuronal signalling

Frontiers in Network Physiology, Год журнала: 2023, Номер 3

Опубликована: Июнь 1, 2023

Neuronal signalling is a key element in neuronal communication and essential for the proper functioning of CNS. Astrocytes, most prominent glia brain play role modulating at molecular, synaptic, cellular, network levels. Over past few decades, our knowledge about astrocytes their has evolved from considering them as merely glue that provides structural support to neurons, elements. Astrocytes can regulate activity neurons by controlling concentrations ions neurotransmitters extracellular milieu, well releasing chemicals gliotransmitters modulate activity. The aim this review summarise main processes through which are function. We will systematically distinguish between direct indirect pathways affect all Lastly, we summarize pathological conditions arise once these impaired focusing on neurodegeneration.

Язык: Английский

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Loss of insulin signaling in astrocytes exacerbates Alzheimer-like phenotypes in a 5xFAD mouse model

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(21)

Опубликована: Май 15, 2023

Brain insulin signaling controls peripheral energy metabolism and plays a key role in the regulation of mood cognition. Epidemiological studies have indicated strong connection between type 2 diabetes (T2D) neurodegenerative disorders, especially Alzheimer’s disease (AD), linked via dysregulation signaling, i.e., resistance. While most focused on neurons, here, we aim to understand astrocytes, glial cell highly implicated AD pathology progression. To this end, created mouse model by crossing 5xFAD transgenic mice, well-recognized that expresses five familial mutations, with mice carrying selective, inducible receptor (IR) knockout astrocytes (iGIRKO). We show age 6 mo, iGIRKO/5xFAD exhibited greater alterations nesting, Y-maze performance, fear response than those transgenes alone. This was associated increased Tau (T231) phosphorylation, Aβ plaque size, association plaques cerebral cortex as assessed using tissue CLARITY brain mice. Mechanistically, vitro IR primary resulted loss reduced ATP production glycolic capacity, impaired uptake both basal insulin-stimulated states. Thus, an important control uptake, thereby contributing pathology, highlighting potential importance targeting site for therapeutics patients T2D AD.

Язык: Английский

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The Role of PGC-1α-Mediated Mitochondrial Biogenesis in Neurons

Neurochemical Research, Год журнала: 2023, Номер 48(9), С. 2595 - 2606

Опубликована: Апрель 25, 2023

Язык: Английский

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