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GASC1, also known as KDM4C/JMJD2C, is a histone demethylase for histone H3 lysine 9 (H3K9) and H3K36. In this study, we observed an increase of GFAP-positive astrocytes in the brain of Gasc1 hypomorphic mutant mice at 2-3 months of age, but not at postnatal day 14 and day 30 by immunohistochemistry. Increases of GFAP-positive astrocytes were widely observed in the forebrain and prominent in such regions as cerebral cortex, caudate putamen, amygdala and diencephalon, but not obvious in hippocampus. Taken together with our observations to be published elsewhere that Gasc1 hypomorphic mutant mice exhibit abnormal behaviors including hyperactivity, persistence and many types of learning and memory deficits and abnormal synaptic functions such as prolonged long-term potentiation, the increase in GFAP-positive astrocytes may help understand their phenotypes, because astrocytes are known to affect synaptic plasticity.
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http://dx.doi.org/10.1111/gtc.12331 | DOI Listing |
J Neurochem
August 2025
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
O-GlcNAcylation is a dynamic and reversible protein posttranslational modification of serine or threonine residues which modulates the activity of transcriptional and signaling pathways and controls cellular responses to metabolic and inflammatory stressors. We and others have shown that O-GlcNAcylation has the potential to regulate autophagy and mitophagy to play a critical role in mitochondrial quality control, but this has not been assessed in vivo in the brain. This is important since mitochondrial dysfunction contributes to the development of neurodegenerative diseases.
View Article and Find Full Text PDFSchizophr Res
July 2025
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address:
Background: The reduced life expectancy observed in individuals with schizophrenia (SCZ) underscores the urgent need for novel therapeutic targets. Emerging evidence suggests that astrocytic dysfunction and immune-inflammatory processes contribute to SCZ pathophysiology. Low-dose methotrexate (MTX), an established immunomodulatory drug used for non-neurological conditions, demonstrated antipsychotic potential in early SCZ.
View Article and Find Full Text PDFAntioxidants (Basel)
July 2025
Institute of General Pathology and Pathophysiology, Moscow 125315, Russia.
Fullerenes and fullerenols exhibit antioxidant and anti-inflammatory properties, making them promising candidates for Alzheimer's disease (AD) therapy. Unlike conventional anti-inflammatory drugs, these compounds have multitargeted effects, including their ability to inhibit amyloid fibril formation. However, few studies have explored their efficacy in high-validity AD models.
View Article and Find Full Text PDFBehav Brain Funct
July 2025
School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.
Background: Parkinson's disease (PD) is an incurable neurological disorder, and current pharmacological therapies primarily address symptoms without halting disease progression. Emerging evidence highlights PD as a neuroinflammatory disease, with chronic brain inflammation preceding the onset of motor dysfunction. This study investigates the role of C18:0 GM3, a long-chain fatty acids-containing ganglioside, in modulating inflammatory responses in PD, exploring its therapeutic potential in mitigating LPS-induced parkinsonism.
View Article and Find Full Text PDFBehav Brain Res
October 2025
Laboratory of Neuroscience, School of Psychology, University of Colima, Colima 28040, Mexico.
Intermittent fasting (IF) is a metabolic intervention that alters systemic and cerebral energy dynamics, promoting neurochemical and cellular adaptations that may influence mood and emotional regulation. Astrocytes, as key regulators of brain metabolism, neurotransmitter clearance, and neuroinflammatory processes, are particularly sensitive to fluctuations in nutrient availability. Dysregulation of astrocytic morphology and glial fibrillary acidic protein (GFAP) expression has been implicated in the pathophysiology of anxiety.
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