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RESEARCH PRODUCT

Transient oligemia is associated with long-term changes in binding densities of cortical inhibitory GABAA receptors in the rat brain

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Recently, we could demonstrate in rats that a short transient oligemic period of only 20-minute duration, induced by systemic hypotension, resulted in a transient decline of spatial memory capacities without any histological damage over a subsequent period of 6 months. In our present study, we checked for more subtle alterations within the highly vulnerable hippocampal CA1 subfield using quantification of neuronal cell density and semi-quantitative analysis of the ischemia-sensitive protein MAP2. Since hippocampal excitatory and inhibitory neurotransmitter receptors are crucially involved in spatial memory processes, quantitative in vitro receptor autoradiography was performed using [(3)H]MK-801, [(3)H]AMPA, and [(3)H]muscimol for labeling of NMDA, AMPA, and GABA(A) receptors, respectively. Ligand binding values were analyzed in the ischemia-sensitive hippocampal formation and in the parietal cortex. Transient oligemia did not cause any reduction of the neuronal cell density in the vulnerable CA1 subfield nor did it cause any significant changes of MAP2 protein expression in the dendritic layers of CA1. After oligemia, hippocampal binding densities of NMDA, AMPA, and GABA(A) receptors remained unchanged in all subfields investigated. Similarly, there was no difference in cortical ligand binding values of the excitatory NMDA and AMPA receptors comparing oligemic to sham-operated control rats. In the parietal cortex, however, transient oligemia caused a significant reduction of [(3)H]muscimol binding values compared to controls. These findings demonstrate long-term changes in receptor binding densities even after short oligemic periods possibly reflecting part of the molecular basis leading to impaired cognitive abilities.