Altered sigma-1 receptor expression in two animal models of cognitive impairment.

Abstract

PURPOSE: Sigma-1 receptors are involved in learning and memory processes. We assessed sigma-1 receptor expression and memory function in two animal models of cognitive impairment. PROCEDURES: Male Wistar-Hannover rats were either lesioned by unilateral injection of N-methyl-D-aspartic acid in the nucleus basalis, or deprived of rapid eye movement sleep for 48 h, using the modified multiple platform method. Sigma-1 receptor expression was examined with the positron emission tomography radiotracer [(11)C]SA4503, immunohistochemistry, and Western blotting. RESULTS: Cortical tracer uptake after 1 week was not significantly affected by lesioning. Immunohistochemistry revealed moderate increases of sigma-1 receptors at bregma level -2.8, in parietal cortex layer V of the lesioned hemisphere. Sleep deprivation lowered passive avoidance test scores and reduced [(11)C]SA4503 accumulation and sigma-1 receptor expression in pons. CONCLUSIONS: Cholinergic lesioning causes an increase of sigma-1 receptor expression in a small cortical area which may be neuroprotective. Sleep deprivation decreases receptor expression in midbrain and pons.