Learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: Interaction of diabetes and ageing

Abstract

Aims/hypothesis. Diabetes mellitus leads to functional and structural changes in the brain which appear to be most pronounced in the elderly. Because the pathogenesis of brain ageing and that of diabetic complications show close analogies, it is hypothesized that the effects of diabetes and ageing on the brain interact. Our study examined the effects of diabetes and ageing on learning and hippocampal synaptic plasticity in rats. Methods. Young adult (5 months) and aged (2 years) rats were examined after 8 weeks of streptozotocin-diabetes. Learning was tested in a Morris water maze. Synaptic plasticity was tested ex vivo, in hippocampal slices, in response to trains of stimuli of different frequency (0.05 to 100 Hz). Results. Statiscally significant learning impairments were observed in young adult diabetic rats compared with controls. These impairments were even greater in aged diabetic animals. In hippocampal slices from young adult diabetic animals long-term potentiation induced by 100 Hz stimulation was impaired compared with controls (138 vs 218% of baseline). In contrast, long-term depression induced by 1 Hz stimulation was enhanced in slices from diabetic rats compared with controls (79 vs 92%). In non-diabetic aged rats synaptic responses were 149 and 93% of baseline in response to 100 and 1 Hz stimulation, compared with 106 and 75% in aged diabetic rats. Conclusion/interpretation. Both diabetes and ageing affect learning the hippocampal synaptic plasticity. The cumulative deficits in learning and synaptic plasticity in aged diabetic rats indicate that the effects of diabetes and ageing on the brain could interact.