Apoptosis of Purkinje and granular cells of the cerebellum following chronic ethanol intake

Cerebellum. 2014 Dec;13(6):728-38. doi: 10.1007/s12311-014-0591-2.

Abstract

Ethanol alters motricity, learning, cognition, and cellular metabolism in the cerebellum. We evaluated the effect of ethanol on apoptosis in Golgi, Purkinje, and granule cells of the cerebellum in adult rats. There were two groups of 20 rats: a control group that did not consume ethanol and an experimental group of UChA rats that consumed ethanol at 10% (<2 g ethanol/kg body weight/day). At 120 days old, rats were anesthetized and decapitated, and their cerebella were collected and fixed. Cerebellar sections were subjected to immunohistochemistry for terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), caspase-3, X-linked inhibitor of apoptosis protein (XIAP), and insulin-like growth factor 1-receptor (IGF-1R); real-time PCR (RT-PCR) to determine caspase-3, XIAP, and IGF-1R gene expression; and transmission electron microscopy (TEM). We identified fragmentation of DNA and an increase in caspase-3 protein and XIAP in Purkinje cells, whereas granule cells exhibited increased caspase-3 and XIAP. IGF-1R expression was unchanged. There was no significant difference in gene expression of caspase-3, XIAP, and IGF-1R. There were an increase in lipid droplets, a reduction in the cellular cytoplasm in electron-dense nuclei, and changes in the myelin sheath in the cerebellar cortex. In conclusion, our data demonstrated that ethanol induced apoptosis in the Purkinje and granule cells of the cerebellum of adult UChA rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Caspase 3 / metabolism
  • Central Nervous System Depressants / administration & dosage*
  • Cerebellum / drug effects*
  • Cerebellum / pathology
  • Cerebellum / physiopathology
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Cytoplasm / pathology
  • DNA Fragmentation / drug effects
  • Ethanol / administration & dosage*
  • Gene Expression / drug effects
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Inhibitor of Apoptosis Proteins / metabolism
  • Lipid Droplets / drug effects
  • Lipid Droplets / metabolism
  • Lipid Droplets / pathology
  • Male
  • Microscopy, Electron, Transmission
  • Myelin Sheath / drug effects
  • Myelin Sheath / pathology
  • Myelin Sheath / physiology
  • Neurons / drug effects*
  • Neurons / pathology
  • Neurons / physiology
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Receptor, IGF Type 1 / metabolism

Substances

  • Central Nervous System Depressants
  • Inhibitor of Apoptosis Proteins
  • Xiap protein, rat
  • Ethanol
  • Receptor, IGF Type 1
  • Casp3 protein, rat
  • Caspase 3