Galactose Impairs Motor Performance and Cerebellar Signaling in Young Male Wistar Rats

Galactosemias are a group of inborn errors of galactose metabolism that causes different motor symptoms such as ataxia, tremor, and fine motor dysfunction. The objective was to investigate the cerebellar damage caused by an acute galactose administration. Thirty-day-old male and female Wistar rats were used. Animals were randomized into the following groups: I) galactose group, receiving a single subcutaneous administration of galactose; II) control group, receiving the vehicle solution under the same conditions. One, 3 or 24 h after administration, the animals were evaluated in the Rotarod test. A lower motor performance was observed in male rats 3 h after a galactose administration. This effect was not seen in females or with galactose exposure for 1 or 24 h. The activities of acetylcholinesterase and choline acetyltransferase were found unaltered in the cerebellum of males 3 h after galactose injection. We also found lower TH levels in cerebellar hemispheres and higher TH levels in cerebellar vermis 3 h after galactose administration in male rats, without differences in MAO-A or MAO-B activities. Galactose administration resulted in lower p-CREB(Ser¹³³) and GAD67 levels in cerebellar hemispheres, without altering these parameters in cerebellar vermis of male rats. Finally, a decrease in TrkB-FL immunocontent (but not of TrkB-T levels) was observed in male cerebellar hemispheres. The absence of neurochemical alterations 1 h or 24 h after galactose administration indicates a transient effect for this hexose. The signs and symptoms of galactosemic patients underscore the need to study galactose effects in males and females and in various brain areas. Our findings enhance the understanding of therapeutic mechanisms of catecholaminergic drugs, which are proposed as a potential therapy for galactosemia.