A Time Course Study of HDAC Expression in Purkinje Neurons from Male Fischer 344 Rats Fed a Liquid Ethanol Diet for 10, 20, or 40 Weeks
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Data from this laboratory show that chronic alcohol exposure in the cerebellum of aging rats is associated with degeneration in the Purkinje neuron (PN) dendritic arbor, decreased number of synapses on PN, and changes in the structure and function of the smooth endoplasmic reticulum in PN dendrites. These changes may be due to ethanol-induced alterations in histone deacetylases (HDACs), which are responsible for gene repression. Eight mo old Fischer 344 rats were treated with standard rat chow (CF), liquid control diet (PF), and a liquid ethanol diet (EF) in which 35% of the calories were from ethanol. Densities/mm of HDAC2, HDAC3, HDAC4, the phosphorylated form of HDAC4, 5 and 7, and acetylated histone 3 (AH3) were determined on 40 um immunostained sections from adult rats exposed to alcohol for 10 (n=30), 20 (n=30), or 40 (n=30) weeks. Corrected total cell fluorescence (CTCF) was also determined for AH3 on sections form the 40 week treatment rats. Densities of HDAC2+ (P<.001) and HDAC3+ (P<.001) PN decreased with age, the phosphorylated form of HDAC4, 5 and 7+ PN (P<.001) increased with age, and HDAC4+ PN did not change with age. There was no effect of alcohol treatment on these densities or on the density of AH3+ PN. CTCF, however, was significantly lower for AH3 (P<.001) in EF rats. The change in expression levels of AH3 with alcohol may be due to increased expression of HDACs not studied decreased expression of histone acetyl transferases (HATs) or a change in the balance between the two. Age related changes in HDAC expression are indicative of epigenetic changes in histone acetylation that would impact the genome by altering gene expression with age.