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 and 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. [Diabetologia
(2000) 43: 500–506]
Keywords Ageing, diabetes mellitus, brain, learning, water maze, hippocampus, synaptic plasticity.
Received: 18 October 1999 and in revised form: 6 December 1999