The gamma-aminobutyric acidA (GABAA)/benzodiazepine (BZ) receptor is a pentamer composed of subunits belonging to several classes (alpha 1-6, beta 1-4, gamma 1-4, delta, and rho 1 and rho 2). In situ hybridization, radioligand autoradiography, and immunocytochemistry were used to examine GABAA/BZ receptor alpha 1, alpha 6, beta 2, beta 3, and gamma 2 subunit expression in murine Purkinje, granule, and deep cerebellar neurons after in vivo ethanol exposure. Chronic ethanol treatment resulted in decreased alpha 1 subunit mRNA expression in each cell type, whereas the expression of alpha 6 and gamma 2 subunit mRNA levels increased; no changes were observed in the expression of beta 2 and beta 3 subunit mRNA. GABA and BZ agonist binding and antibody staining paralleled the changes in mRNA levels. Acute ethanol injection resulted in increased expression of alpha 1 and beta 3 mRNAs, whereas levels of alpha 6, beta 2, and gamma 2 mRNAs remained stable. Our results indicate that, in cerebellar neurons, the expression of specific GABAA/BZ receptor subunit mRNAs, polypeptides, and binding sites is independently regulated by in vivo administration of alcohol. The observed changes were not restricted to any one cerebellar cell type, because subunit expression in Purkinje, granule, and deep cerebellar cells was similarly affected.
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http://dx.doi.org/10.1046/j.1471-4159.1995.65031229.x | DOI Listing |
Genes Dev
January 2025
Laboratory of Developmental Neurobiology, The Rockefeller University, New York, New York 10065, USA;
Neuronal maturation is guided by changes in the chromatin landscape that control developmental gene expression programs. Histone bivalency, the co-occurrence of activating and repressive histone modifications, has emerged as an epigenetic feature of developmentally regulated genes during neuronal maturation. Although initially associated with early embryonic development, recent studies have shown that histone bivalency also exists in differentiated and mature neurons.
View Article and Find Full Text PDFMol Biol Cell
January 2025
Department of Cell Biology, Emory University, 615 Michael St, Atlanta, GA, USA, 30322.
Rare inherited diseases caused by mutations in the copper transporters (CTR1) or induce copper deficiency in the brain, causing seizures and neurodegeneration in infancy through poorly understood mechanisms. Here, we used multiple model systems to characterize the molecular mechanisms by which neuronal cells respond to copper deficiency. Targeted deletion of CTR1 in neuroblastoma cells produced copper deficiency that produced a metabolic shift favoring glycolysis over oxidative phosphorylation.
View Article and Find Full Text PDFMol Genet Metab
January 2025
Image Processing & Analysis Core (iPAC), Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA. Electronic address:
Objective: GM1 gangliosidosis is a rare lysosomal storage disorder characterized by the accumulation of GM1 gangliosides in neuronal cells, resulting in severe neurodegeneration. Currently, limited data exists on the brain volumetric changes associated with this disease. This study focuses on the late-infantile and juvenile subtypes of type II GM1 gangliosidosis, aiming to quantify brain volumetric characteristics to track disease progression.
View Article and Find Full Text PDFBMC Med
January 2025
Sleep Medicine Center, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, NO.28 Qiaozhong Mid Road, Guangzhou, Guangdong, 510160, China.
Background: Obstructive sleep apnea (OSA) is linked to brain alterations, but the specific regions affected and the causal associations between these changes remain unclear.
Methods: We studied 20 pairs of age-, sex-, BMI-, and education- matched OSA patients and healthy controls using multimodal magnetic resonance imaging (MRI) from August 2019 to February 2020. Additionally, large-scale Mendelian randomization analyses were performed using genome-wide association study (GWAS) data on OSA and 3935 brain imaging-derived phenotypes (IDPs), assessed in up to 33,224 individuals between December 2023 and March 2024, to explore potential genetic causality between OSA and alterations in whole brain structure and function.
Brain Res
January 2025
Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India. Electronic address:
Neurodegenerative disorders are characterized by a progressive loss of neurons, causing substantial deficits in motor and cognitive functioning. Bilirubin is a yellow by-product of heme, existing in two primary isoforms namely unconjugated and conjugated, while initially produced unconjugated isomer is lipophilic and cytotoxic in nature. At physiological levels, bilirubin has an important role in brain function by acting as a powerful antioxidant, preventing brain tissues from oxidative damage by eliminating reactive oxygen species (ROS).
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