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The cerebellum is fundamental for motor coordination and therefore crucial in ethanol-induced ataxia. Ethanol contributes to cerebellar pathophysiology. Fragile-X Mental Retardation protein (FMRP) is a complex regulator of RNA and synaptic plasticity implicated in Fragile-X Tremor and Ataxia Syndrome, a phenotype featuring increased Fmr1 mRNA expression. Recent studies have implicated glutamatergic targets of FMRP in hereditary cerebellar ataxias including the main cerebellar excitatory amino acid (Eaa1) transporter and a subtype of metabotropic glutamate receptor (Grm5). However, ethanol-induced changes in cerebellar Fmr1 expression and its epigenetic regulation have not been investigated. Here, we examined the effects of acute ethanol exposure on ataxic behavior, gene expression, and epigenetic regulation of the Fmr1 gene and its glutamatergic targets in the rat cerebellum.
This article was published in the following journal.
Name: Alcoholism, clinical and experimental research
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Alcohol use disorder (AUD) and major depressive disorder (MDD) are prevalent, debilitating, and highly comorbid disorders. The molecular changes that underlie their comorbidity are beginning to emerge...
The fragile X associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disease associated with the repetition of CGG triplets (55-200 CGG repetitions) in the FMR1 gene. The premutation of the ...
Fragile X syndrome (FXS) is caused primarily by a CGG repeat expansion in the FMR1 gene that triggers its transcriptional silencing. In order to investigate the regulatory layers involved in FMR1 inac...
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Compounds that inhibit HISTONE DEACETYLASES. This class of drugs may influence gene expression by increasing the level of acetylated HISTONES in specific CHROMATIN domains.
A class II histone deacetylase that removes acetyl groups from N-terminal LYSINES of HISTONE H2A; HISTONE H2B; HISTONE H3; and HISTONE H4. It plays a critical role in EPIGENETIC REPRESSION and regulation of GENETIC TRANSCRIPTION, as well as CELL MOTILITY through deacetylation of TUBULIN. It also targets misfolded proteins for clearance by AUTOPHAGY when MOLECULAR CHAPERONE-mediated folding is overwhelmed.
A Krupple-type transcription factor consisting of an N-terminal BTB DOMAIN and nine CYS2-HIS2 ZINC FINGERS. It localizes to the nucleus and regulates cell cycle progression and gene expression for tissue development and homeostasis; it may also function as an epigenetic regulator through its interactions with HISTONE DEACETYLASE. Genetic rearrangements involving the ZBTB16 gene are associated with ACUTE PROMYELOCYTIC LEUKEMIA.
A non-metabolizable galactose analog that induces expression of the LAC OPERON.
An acute brain syndrome which results from the excessive ingestion of ETHANOL or ALCOHOLIC BEVERAGES.
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The development and maintenance of an organism is orchestrated by a set of chemical reactions that switch parts of the genome off and on at strategic times and locations. Epigenetics is the study of these reactions and the factors that influence them. ...