Hippocampal synaptic plasticity in streptozotocin-diabetic rats: impairment of long-term potentiation and facilitation of long-term depression.
Streptozotocin-diabetic rats, an animal model for diabetes mellitus, show learning deficits and impaired long-term potentiation in the CA1-field of the hippocampus. The present study aimed to further characterize the effects of streptozotocin-diabetes on N-methyl-D-aspartate receptor-dependent long-term potentiation in the CA1-field, to extend these findings to N-methyl-D-aspartate receptor-dependent and independent long-term potentiation in other regions of the hippocampus and to examine effects on long-term depression. First, the effect of diabetes duration on long-term potentiation in the CA1-field was determined. A progressive deficit was observed after a diabetes duration of six to eight weeks, which reached a maximum after 12 weeks of diabetes and remained stable thereafter. Next, long-term potentiation was examined in the dentate gyrus and in the CA3-field after 12 weeks of diabetes. Both were found to be impaired compared to controls. Finally, long-term depression was examined in the CA1-field of the hippocampus after 12 weeks of diabetes and found to be enhanced in slices from diabetic rats compared to controls. Changes in synaptic plasticity were observed in hippocampal slices from streptozotocin-diabetic rats. Expression of N-methyl-D-aspartate receptor-dependent long-term potentiation was impaired in the CA1-field and dentate gyrus and expression of N-methyl-D-aspartate receptor-independent long-term potentiation was impaired in the CA3-field. In contrast, expression of long-term depression was facilitated in CA1. It is suggested that this combination of changes in plasticity may reflect alterations in intracellular signalling pathways.
Kamal
A
A
Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Utrecht University, The Netherlands.
Biessels
G J
GJ
Urban
I J
IJ
Gispen
W H
WH
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006624:Hippocampus / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology*; D013997:Time Factors