Hyperinsulinemia in rats causes impairment of spatial memory and learning with defects in hippocampal synaptic plasticity by involvement of postsynaptic mechanisms.
In addition to its peripheral metabolic functions, insulin acts as a central neuromodulator and affects synaptic plasticity of the hippocampal neurons. In this study, hyperinsulinemic obese zucker rats (OZR) with autosomal recessive mutation of the fa-gene were tested in water maze for learning and memory. The animals were then decapitated and hippocampal slices were prepared for electrophysiological examination. In the water maze test, the OZR performed less efficient than their counter lean control rats (LCR). The OZR showed prolonged latency and increased distance swam to reach a hidden platform. In the electrophysiological experiments, the hippocampal slices were examined for paired-pulse facilitation (PPF), long-term potentiation (LTP), and depression expression. The results showed that while the PPF (thus mainly the presynaptic mechanisms) was not affected, the LTP expression (169.9 ± 16.6 vs. 310.7 ± 2.4 %) and the synaptic plasticity range (69.2 vs. 211.2 %) were both reduced in the OZR animals compared to the LCR. It is concluded that hyperinsulinemia in the OZR resulted in defects in hippocampal synaptic plasticity associated with deterioration in spatial learning and memory functions.
Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neurosciences, University Medical Center Utrecht, Utrecht, The Netherlands.
Amer
A
Kamal
Geert M J
GM
Ramakers
Willem Hendrik
WH
Gispen
Geert Jan
GJ
Biessels
Amer
A
Al Ansari
D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D006946:Hyperinsulinism / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008569:Memory Disorders / Q000378:metabolism / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D011924:Rats, Zucker; D013037:Spatial Behavior / Q000502:physiology*; D013569:Synapses / Q000502:physiology