D-Galactose Causes Motor Coordination Impairment, and Histological and Biochemical Changes in the Cerebellum of Rats

Mol Neurobiol. 2017 Aug;54(6):4127-4137. doi: 10.1007/s12035-016-9981-4. Epub 2016 Jun 20.

Abstract

Classical galactosemia is an inborn error of carbohydrate metabolism in which patients accumulate high concentration of galactose in the brain. The most common treatment is a galactose-restricted diet. However, even treated patients develop several complications. One of the most common symptoms is motor coordination impairment, including affected gait, balance, and speech, as well as tremor and ataxia. In the present study, we investigated the effects of intracerebroventricular galactose administration on motor coordination, as well as on histological and biochemical parameters in cerebellum of adult rats. Wistar rats received 5 μL of galactose (4 mM) or saline by intracerebroventricular injection. The animals performed the beam walking test at 1 and 24 h after galactose administration. Histological and biochemical parameters were performed 24 h after the injections. The results showed motor coordination impairment at 24 h after galactose injection. Galactose also decreased the number of cells in the molecular and granular layers of the cerebellum. The immunohistochemistry results suggest that the cell types lost by galactose are neurons and astrocytes in the spinocerebellum and neurons in the cerebrocerebellum. Galactose increased active caspase-3 immunocontent and acetylcholinesterase activity, decreased acetylcholinesterase immunocontent, glutathione, and BDNF levels, as well as caused protein and DNA damage. Our results suggest that galactose induces histological and biochemical changes in cerebellum, which can be associated with motor coordination impairment.

Keywords: Acetylcholinesterase; Apoptosis; BDNF; Caspase-3; Cell damage; Galactose; Motor coordination.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Antigens, Nuclear / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • Caspase 3 / metabolism
  • Cell Count
  • Cerebellum / drug effects
  • Cerebellum / pathology*
  • Cerebellum / physiopathology*
  • DNA Damage
  • Galactose / administration & dosage
  • Galactose / pharmacology*
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutathione / metabolism
  • Injections, Intraventricular
  • Male
  • Motor Activity / drug effects*
  • Nerve Tissue Proteins / metabolism
  • Rats, Wistar
  • Sulfhydryl Compounds / metabolism

Substances

  • Antigens, Nuclear
  • Brain-Derived Neurotrophic Factor
  • Glial Fibrillary Acidic Protein
  • Nerve Tissue Proteins
  • Rbfox3 protein, rat
  • Sulfhydryl Compounds
  • Acetylcholinesterase
  • Caspase 3
  • Glutathione
  • Galactose