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Ngn2 and Isl1-mediated astrocyte-to-neuron conversion in vivo promotes functional recovery after spinal cord injury.

Adult neurogenesis plays a crucial role in maintaining brain homeostasis and can respond to neurogenic injuries. However, the adult mammalian spinal cord has extremely limited intrinsic neurogenic ability. Here, we show that in vivo astrocyte-to-neuron conversion can regenerate functional neurons after spinal cord injury (SCI) through CRISPRa-mediated activation of endogenous transcription factors Ngn2 and Isl1. Lineage tracing confirms that the origin of these induced neurons is reactive astrocytes, rather than endogenous neurons. Furthermore, these induced neurons express specific markers of…

Histone lactylation exacerbates cerebral ischemia-reperfusion injury via NSUN2-mediated epigenetic activation of astrocytic neuroinflammation.

OBJECTIVE: This study investigates how histone lactylation regulates NOP2/Sun RNA methyltransferase family member 2 (NSUN2)-mediated 5-methylcytosine (m5C) modification and promotes astrocyte-driven neuroinflammation in cerebral ischemia - reperfusion (I/R) injury. METHODS: A middle cerebral artery occlusion - reperfusion (MCAO/R) model was used to induce I/R injury. Mice were treated with NSUN2 knockdown/overexpression or the lactate dehydrogenase inhibitor oxamate. In vitro, oxygen - glucose deprivation/reperfusion (OGD/R) models were established in C8-D1A astrocytes and BV2 microglia. Neur…

Intramural hematomas and astrocytic infiltration precede perivascular inflammation in a rat model of repetitive low-level blast injury.

In modern war theaters, exposures to blast overpressures are one of the most common causes of brain injury. These pervasive events result in … ted subacute effects of blast exposure included increased MMP-9 expression in perivascular reactive astrocytes and the extension of astrocytic processes through the layers of affected vessels. These results, in combination with normal levels of proinflammatory cytokines and the absence of proinflammatory MHC II-expressing microglia, suggest an astrocytic rol …

Cerebrospinal fluid neuronal pentraxin levels are associated with tau pathology via microglia-astrocyte signaling in alzheimer's disease.

BACKGROUND: Recent studies have reported that Neuronal Pentraxin 2 (NPTX2), a synapse-associated protein, can significantly predict the progression of cognitive decline. However, the role of the NPTX protein family in the pathological progression of Alzheimer's Disease (AD) in humans remains unclear. METHODS: This study included 263 participants from the Alzheimer's Disease Neuroimaging Initiative, including cognitively normal, mild cognitive impairment, and AD individuals, with a mean age of 73.99 ± 7.43 years. Cerebrospinal fluid (CSF) NPTX proteins and Glial Fibrillary Acidic Protein (GFAP

Inhibition of p38α MAPK increases short-term astrocyte reactivity: the exploratory VIP trial in early Alzheimer's disease.

BACKGROUND: Neuro-inflammation is an early mechanistic target in Alzheimer’s disease (AD). However, the effect of anti-inflammatory drugs on biomarkers of neuro-inflammation has yet to be described. Biomarkers of neuro-inflammation showed distinct evolution over the course of AD, suggesting that anti-inflammatory interventions could be beneficial or interfere with mechanisms of immune defense. METHODS: We conducted a pilot and exploratory phase II trial to evaluate the short-term effects of neflamapimod, a drug known to inhibit the neuro-toxic pro-inflammatory properties of the p38α MAPK. Part

Systematic review and meta-analysis of microbiota-gut-astrocyte axis perturbation in neurodegeneration, brain injury, and mood disorders.

BackgroundAstrocytes are essential for preserving homeostasis, maintaining the blood-brain barrier, and they are a key element of the tripartite neuronal synapse. Despite such multifaceted roles, their importance as contributors to the microbiota-gut-brain axis studies, which typically focus on microglia and neurons, has been largely overlooked. This meta-analysis provides the first systematic review of the microbiota-gut-astrocyte (MGA) axis in vivo, integrating findings across distinct neurological diseases.MethodsA systematic narrative review was conducted per PRISMA guidelines. The search …

Ethanol induces neuroimmune dysregulation and soluble TREM2 generation in a human iPSC neuron, astrocyte, microglia triculture model.

Alcohol use disorders (AUDs) affect substantial populations worldwide and increase the risk of developing cognitive impairments and alcohol-associated dementia. While chronic inflammatory signaling likely plays an important role in alcohol-associated neurological sequalae, the precise mechanisms underlying alcohol-associated neuropathology remain enigmatic. We hypothesize that alcohol leads to neuroimmune dysregulation among neurons, astrocytes, and microglia; and is perpetuated by innate immune signaling pathways involving cell-cell signaling. To investigate how alcohol dysregulates neuroimmu…

Ethanol induces neuroimmune dysregulation and soluble TREM2 generation in a human iPSC neuron, astrocyte, microglia triculture model.

Alcohol use disorders (AUDs) affect substantial populations worldwide and increase the risk of developing cognitive impairments and alcohol-associated dementia. While chronic inflammatory signaling likely plays an important role in alcohol-associated neurological sequalae, the precise mechanisms underlying alcohol-associated neuropathology remain enigmatic. We hypothesize that alcohol leads to neuroimmune dysregulation among neurons, astrocytes, and microglia; and is perpetuated by innate immune signaling pathways involving cell-cell signaling. To investigate how alcohol dysregulates neuroimmu…

Association among cardiorespiratory fitness, plasma biomarkers of pathology and astrocyte reactivity, and cognition in autosomal-dominant Alzheimer's disease.

BackgroundHigh cardiorespiratory fitness has been associated with greater neuroplasticity, and slower neurodegeneration and cognitive decline in healthy adults. Yet, less is known about whether low-to-intermediate cardiorespiratory fitness is associated with lower markers of disease progression in the preclinical stage of Alzheimer's disease (AD).ObjectiveWe investigated whether cardiorespiratory fitness was associated with plasma biomarkers for AD-related pathology, neural injury and astrocyte reactivity, and episodic memory in Presenilin-1 E280A carriers without dementia from the world's lar

Interrogating mediators of single-cell transcriptional changes in the acute damaged cerebral cortex: Insights into endothelial-astrocyte interactions.

Traumatic brain injury (TBI) induces complex cellular and molecular changes, challenging recovery and therapeutic development. Although mole … xperimental TBI model, we mapped transcriptional changes across various cell types, with a focus on astrocytes and ECs. Our analysis reveals that EC-specific knockout (KO) of EphA4 triggers significant alterations in astrocyte gene expression and shifts predominate subclusters. We identified six distinct astrocyte clusters (C0-C5) in the damaged cortex inclu …

Astrocyte-derived Exosomal GJA1-20 k Targets Pink1-mediated Mitophagy to Attenuate Traumatic Brain Injury.

Connexin 43 (Cx43), particularly its truncated isoform GJA1-20 k, has shown promise in mitigating neuronal injury through mitochondrial regulation. This study aimed to investigate the therapeutic potential of astrocyte-derived extracellular vesicles (EVs) enriched with GJA1-20 k (Exo-GJA1-20 k) for treating traumatic brain injury (TBI). Primary astrocytes were isolated and transfected with an adeno-associated viral vector to overexpress GJA1-20 k. EVs were extracted and characterized using nanoparticle tracking analysis and Western blotting. A controlled cortical impact (CCI) model of TBI was …

CXCR3 Deficiency Alleviates Retinal Ganglion Cell Loss by Regulating Neuron-Astrocyte Communication in a Mouse Model of Glaucoma.

PURPOSE: Glaucoma is characterized by progressive retinal ganglion cell (RGC) death and optic nerve degeneration. Chemokines are a family of … fferentially expressed chemokines. A mouse model of microbead-induced glaucoma and primary RGCs and astrocytes were used to assess the role of the C-X-C motif chemokine ligand 10 (CXCL10)/C-X-C motif chemokine receptor 3 (CXCR3) axis in disease. RESULTS: Several chemokines were significantly upregulated during disease progression, including CXCL10, previous …

Ultrastructural characterization of peri-synaptic astrocytic processes around cerebellar Purkinje spines under resting and stimulated conditions.

In mammalian brains, astroglia presence near glutamatergic excitatory synapses has generated the term "tripartite" junctions, based on the close association of astrocytic processes near the active zone formed by presynaptic axonal terminal and postsynaptic dendritic spines. One major function of these astrocytic processes is to take up glutamate that spill out of the synaptic cleft during activity, via glutamate transporters located on astroglial plasma membrane. Comapred to other regions of the brain, the cerebellar Purkinje spines in the molecular layer are virtually completely ensheathed by

Mycobacterium tuberculosis-induced oligodendrocyte apoptosis promotes astrocyte-mediated cell-in-cell formation and phagocytosis in tuberculous meningitis.

OBJECTIVE: To determine whether cell-in-cell (CIC) structures exist in tuberculous meningitis (TBM) and to explore their clinical significance. METHODS: Pathological brain biopsies from TBM patients were retrospectively analyzed using H&E and immunohistochemistry, with a focus on CIC structures. Multicolor immunofluorescence and in vitro coculture of astrocytes and oligodendrocytes were employed to explore CIC characteristics and underlying mechanisms. Flow cytometry was used to assess Bacillus Calmette-Guérin (BCG)-induced oligodendrocyte apoptosis. RESULTS: CIC structures (CICs) were ident…

Metal-organic framework UiO-66 dose-dependently mitigates oxidative stress and astrocyte activation in the rat hippocampus.

Although the metal-organic framework (MOF) UiO-66 is used as a drug delivery system, its potential harmful effects on the nervous system remain underexplored. This study evaluated the subacute impact of UiO-66 nanoparticles on working and spatial memory, neuronal integrity, oxidative stress, and astrocyte activation in the rat hippocampus. Fifty-six Wistar rats were randomly assigned to four groups. The control group received intravenous injections of normal saline, while the treatment groups were administered UiO-66 at doses of 1, 10, or 50 mg/kg over two weeks (four injections, twice weekly)

Нацеливание на астроцитический CLC2 (CLCN2) восстанавливает регенерацию миелина посредством ингибиции SPP1/CD44 сигнализирующего пути в лейкоэнцефалопатии.

Аккумулирование миелиновых повреждений и поврежденное ремиелионирование являются центральными патологическими особенностями лейкоэнцефалопатии, включая множественный склероз и болезнь Александра, где астроциты играют важную роль в поддержании гомеостаза центральной нервной системы и посредничестве взаимодействия астроцита-олигодендроцитов. Хлорид Ion Channel 2 (CIC-2), кодируемый CLCN2, функционально выражается в астроцитах и, вероятно, имеет решающее значение для целостности белого вещества; однако его точные роли и взаимодействие остаются неясными. Уточнение механизмов, с помощью которых аст

Совпадение в аннотации оригинала
Accumulating myelin damage and impaired remyelination are central pathological features of leukoencephalopathies, including Multiple Sclerosis and Alexander Disease, where astrocytes play essential roles in maintaining central nervous system homeostasis and mediating astrocyte-oligodendrocyte interactions. Chloride Ion Channel 2 (ClC-2), encoded by CLCN2, is…

The potential role of S-nitrosoglutathione reductase in astrocyte BAFF expression and B cell activation in experimental autoimmune encephalomyelitis.

B cell-activating factor (BAFF) is a key mediator of B cell-driven autoimmune pathology. In mice with experimental autoimmune encephalomyelitis (EAE), a widely used model of multiple sclerosis (MS), we observed a pronounced accumulation of B cells within the spinal cord, alongside elevated BAFF expression, particularly in GFAP+ activated astrocytes located in the subpial-region. This upregulation of BAFF coincided with the infiltration of CD4+ T cells, notably Th1 cells producing IFNγ, a cytokine critical for inducing BAFF gene expression in astrocytes. Concurrently, elevated BAFF levels in th…

NR1H4 ameliorates Parkinson's disease via inhibiting astrocyte activation and neuroinflammation in a CEBPβ/NF-κB dependent manner.

Parkinson's Disease (PD) is a degenerative disease driven by neuroinflammation. Nuclear receptor subfamily 1 group H member 4 (NR1H4), a nuc … suggested that Nr1h4 knockdown led to inflammatory response, reactive oxygen species generation and astrocytes activation whereasNr1h4 overexpressionhad the opposite effects. The results of RNA-seq on astrocytes revealed that NR1H4 manipulated neuroinflammation in a CEBPβ/NF-κB dependent manner. Additionally, pharmacological activation of NR1H4 via Obetichol …

Inhibition of phosphodiesterase 4 attenuates aquaporin 4 expression and astrocyte swelling following cerebral ischemia/reperfusion injury.

We have previously shown that phosphodiesterase 4 (PDE4) inhibition protects against neuronal injury in rats following middle cerebral arter … oxO3a) were increased. In addition, Roflu reduced cell volume and the expression of AQP4 in primary astrocytes undergoing oxygen and glucose deprivation/reoxygenation (OGD/R). Consistently, PDE4B knockdown showed similar effects as PDE4 inhibition; and PDE4B overexpression rescued the inhibitory role of PDE4B knockdown on AQP4 expression. We then found that …

Sevoflurane postconditioning mitigates neuronal hypoxic-ischemic injury via regulating reactive astrocytic STAT3 protein modification.

Astrocyte activation plays a pivotal role in accelerating the cascade of neuroinflammation associated with the development of hypoxic-ischemic brain injury. This study aimed to investigate the mechanism by which sevoflurane postconditioning mitigates neuronal damage through astrocytes by regulating reactive astrocytic Signal Transducer and Activator of Transcription 3 (STAT3) modifications. A modified Rice‒Vannucci model in rats and a conditioned culture system established by subjecting primary astrocytes to oxygen glucose deprivation, followed by using the conditioned medium to culture the ne…