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Galactose Impairs Motor Performance and Cerebellar Signaling in Young Male Wistar Rats.
Bruna Klippel Ferreira1, Thiago Paz-Simões1, Thairine Neves Melo1
1Laboratório de Erros Inatos Do Metabolismo, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal Do Rio de Janeiro, Av. Carlos Chagas Filho, Rio de Janeiro, RJ, 373, Brazil.
Molecular Neurobiology
|February 6, 2025
Summary
Acute galactose exposure transiently impairs motor performance in male rats, affecting cerebellar neurochemistry. This study highlights sex-specific effects and transient impacts of galactose, crucial for understanding galactosemia and potential therapies.
Area of Science:
- Neuroscience
- Metabolic Disorders
- Toxicology
Background:
- Galactosemias are inherited metabolic disorders affecting galactose processing.
- These conditions can lead to significant neurological and motor deficits.
- Understanding acute galactose toxicity is vital for managing galactosemia.
Purpose of the Study:
- To investigate cerebellar damage and neurochemical alterations following acute galactose administration.
- To assess sex-specific differences in response to galactose exposure.
- To determine the temporal dynamics of galactose-induced neurochemical changes.
Main Methods:
- Acute galactose or vehicle was administered subcutaneously to 30-day-old male and female Wistar rats.
- Motor performance was evaluated using the Rotarod test at 1, 3, and 24 hours post-administration.
- Cerebellar tissue was analyzed for neurotransmitter levels (TH, MAO-A/B), enzyme activities (AChE, ChAT), and protein expression (p-CREB, GAD67, TrkB).
Main Results:
- Male rats exhibited reduced motor performance 3 hours after galactose administration, an effect not observed in females or at other time points.
- Galactose altered tyrosine hydroxylase (TH) levels in specific cerebellar regions (hemispheres and vermis) and reduced p-CREB, GAD67, and TrkB-FL in male cerebellar hemispheres.
- Neurochemical alterations were transient, with no significant changes observed at 1 or 24 hours post-galactose exposure.
Conclusions:
- Acute galactose administration causes transient, sex-specific motor deficits and neurochemical changes in the male rat cerebellum.
- These findings underscore the importance of considering sex and brain region in galactosemia research.
- The study provides insights into potential therapeutic targets, such as catecholaminergic pathways, for galactosemia.
