Astrocyte activation but not neuronal impairment occurs in the hippocampus of mice after 2Â weeks of d-galactose exposure

AimsThe objective of this study is to prove that activation of astrocytes precedes neuron cell death in the neurodegenerative process induced by d-galactose (d-gal) exposure.Main methodsMale adult mice were given intraperitoneal injection of d-gal (200 mg/kg per day) for 2 weeks. The whole brain homogenate and hippocampal sections were then prepared for biochemical analyses, immunohistochemistry and electron microscopy, respectively.Key findingsThere were no statistically significant differences in brain oxidative and antioxidative parameters between d-gal-treated mice and saline controls. There was also lack of morphological impairment in hippocampal neuronal soma, dendrites and synapses in the model mice. In contrast, hippocampal astrocytes were dramatically activated, and perisynaptic processes of astrocytes were swelling as revealed by ultrastructural analysis. Moreover, d-gal-treated group showed increases in immunostaining levels of glutamate transporter-1 and aquaporin-4 in the hippocampus, which might increase uptake of glutamate from the synaptic cleft into astrocytes.SignificanceThese results reveal that astrocytes undergo structural and biochemical changes while no impairment of neuronal elements occurs after 2 weeks of d-gal exposure. Thus, targeting astrocytes may be a promising strategy for the treatment of neurodegenerative diseases at the early stages.