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

• Published in: Molecular neurobiology Vol. 54; no. 6; pp. 4127 - 4137
• Main Authors: Rodrigues, André Felipe, Biasibetti, Helena, Zanotto, Bruna Stela, Sanches, Eduardo Farias, Schmitz, Felipe, Nunes, Vinícius Tejada, Pierozan, Paula, Manfredini, Vanusa, Magro, Débora Delwing Dal, Netto, Carlos Alexandre, Wyse, Angela T.S.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2017; Springer Nature B.V
• Subjects: Acetylcholinesterase; Acetylcholinesterase - metabolism; Animal cognition; Animals; Antigens, Nuclear - metabolism; Apoptosis; Astrocytes; Ataxia; Balance; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Carbohydrate metabolism; Carbohydrates; Caspase; Caspase 3 - metabolism; Caspase-3; Cell Biology; Cell Count; Cerebellum; Cerebellum - drug effects; Cerebellum - pathology; Cerebellum - physiopathology; Complications; Coordination; D-Galactose; DNA Damage; Gait; Galactose; Galactose - administration & dosage; Galactose - pharmacology; Galactosemia; Glial Fibrillary Acidic Protein - metabolism; Glucose; Glutathione; Glutathione - metabolism; Histology; Immunohistochemistry; Impairment; Injection; Injections, Intraventricular; Male; Motor ability; Motor Activity - drug effects; Motor task performance; Nerve Tissue Proteins - metabolism; Neurobiology; Neurology; Neurons; Neurosciences; Rats; Rats, Wistar; Rodents; Saline solutions; Speech; Sulfhydryl Compounds - metabolism; Tremor; Walking; BDNF; Cell damage; Motor coordination; Galactose; Acetylcholinesterase; Caspase-3; Apoptosis
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-016-9981-4

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.