Diabetes onset influences hippocampal synaptic plasticity in streptozotocin-treated rats.
Children with type 1 diabetes mellitus (DM) are at risk of developing cognitive difficulties. Although a diabetes onset of patient influences cognitive difficulties, synaptic properties related to the age of diabetes onset remain unknown. Here we showed that synaptic plasticity including long-term potentiation (LTP) or long-term depression (LTD), and excitatory synaptic transmission at Schaffer collateral-CA1 (SC-CA1) synapses in hippocampal slices were affected by age of onset in rats with streptozotocin-induced diabetes (STZ-rats), compared with age-matched control rats. LTP was impaired and the ratio of AMPA receptor-mediated EPSCs relative to N-methyl-d-aspartate (NMDA) receptor-mediated EPSCs (the AMPA/NMDA ratio) decreased in young adult-onset STZ-rats, whereas LTD was impaired and both AMPA receptor-mediated and NMDA receptor-mediated EPSCs increased in juvenile-onset STZ-rats. Furthermore, impaired LTD of juvenile-onset STZ-rats was restored with an NMDA receptor antagonist. These results suggest that the pathophysiology of diabetes-induced cognitive difficulties varies with the age of diabetes onset.
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
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S
Sasaki-Hamada
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H
Sacai
J-I
JI
Oka
D000367:Age Factors; D017668:Age of Onset; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000473:pathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D066298:In Vitro Techniques; D009434:Neural Pathways / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D017470:Receptors, Glutamate / Q000378:metabolism; D013311:Streptozocin / Q000633:toxicity*; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010852:Picrotoxin; D017470:Receptors, Glutamate; D013311:Streptozocin; D014633:Valine; C056639:2-amino-5-phosphopentanoic acid