Authors: Raquel Baeta-Corral, Rafael Castro-Fuentes, Lydia Giménez-Llort.
Summary: For almost twenty years, chronic systemic D-galactose, a monosaccharide abundantly present in milk products, fruits and vegetables, has been used as a tool to achieve models of accelerated aging. Its neurotoxicity, induced by abnormal accumulation of ROS and AGEs, has been widely reported. However, behavioral outcomes are still controversial and little is known about sex-dependent vulnerability. We performed a comprehensive behavioral and multi-functional screening of the chronic effects of low (50 mg/kg) and high (100 mg/kg) doses of D-galactose in 6-month-old male and female gold-standard C57BL/6 mice. Twelve classical tests with convergent validity analyzed sensorimotor, emotional and cognitive domains, indicating the existence of thresholds of response. Distinct vulnerability patterns were found in a selective sex- and dose-dependent manner. In males, D-galactose induced sensorimotor impairment and immunoendocrine senescence, but the low dose resulted in improved learning and memory. Oppositely, D-galactose treated females exhibited a dose-dependent worse motor and spatial learning, but improved memory. Behavioral outcomes items point at distinct neuronal substrates underlying the functional capacity of D-galactose treated animals to meet task-dependent performance demands. They support that males and females can be regarded as two exceptional natural scenarios to study the functional interplay in the crosstalk of homeostatic networks in aging.
Source: J Gerontol A Biol Sci Med Sci, 2018