Deregulation of Neuroinflammatory and Neurotrophic Factors as Biological Events Triggered by D-Galactose Chronic Administration in Wistar Rats

Abstract

The chronic administration of D-galactose (D-gal) is widely used to model brain senescence in rodents. However, the effects of prolonged oral exposure of D-gal on the neuroinflammatory cytokines in rats remain poorly characterized. Therefore, we administered D-gal (100 mg/kg) in male Wistar rats aged 3-4 months, via oral gavage once a day for 1, 2, 4, 6, or 8 weeks. Cytokine and neurotrophin levels were analyzed using the ELISA method. D-gal administrations for 4, 6, and 8 weeks significantly increased interleukin -1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-4 (IL-4) levels in the frontal cortex and hippocampus. In addition, 4, 6, and 8 weeks of D-gal administration significantly increased interleukin-10 (IL-10) levels in the frontal cortex; however, in the hippocampus, only 6 and 8 weeks of D-gal administration significantly increased the IL-10 levels. In terms of neurotrophin levels, our results demonstrated that 1 week of D-gal administration significantly increased Brain-derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in the hippocampus. In the frontal cortex, D-gal increased BDNF levels when administered for 1 and 2 weeks and increased NGF levels when administered for only 2 weeks. However, we observed a reduction of BDNF, NGF, and Glial cell line-derived Neurotrophic Factor (GDNF) levels after 6 and 8 weeks of D-gal treatment in the frontal cortex. Moreover, GDNF levels also were reduced after 4 weeks of D-gal administration. These findings suggest that oral D-gal exposure disrupts the balance of cytokines and neurotrophins, which may be an essential mechanism in brain aging and neurodegenerative processes.

Keywords: Aging; D-galactose; Inflammatory cytokine; Neurotrophins; Senescence.