Chronic systemic injection of D-galactose impairs the septohippocampal cholinergic system in rats

Accumulated evidence indicates chronic systemic injection of D-galactose mimics aging progress induced by oxidative stress. We addressed whether memory impairment in this model was associated with the cholinergic septohippocampal degeneration. Rats injected with D-galactose for 6 weeks showed impairment of spatial learning and memory as measured by the water maze test. Correspondingly, anti-choline acetyltransferase immunohistochemistry demonstrated a severe loss of cholinergic terminals in the hippocampus accompanied by a mild cholinergic neuronal atrophy and loss in the medial septum and the nucleus of the vertical limb of the diagonal band of Broca. A major synaptic degeneration in the hippocampus was confirmed by ultrastructural analysis. These findings provide neuropathological evidence for rodents with chronic injection of D-galactose as a promising model for brain aging and age-related neurodegeneration.