Preserved sigma1 (σ1) receptor expression and behavioral efficacy in the aged C57BL/6 mouse

The sigma1 (σ1) receptor represents a unique intracellular neuronal protein modulating several neurotransmitter responses with relevant effects on cognitive functions. We examined here its expression and behavioral efficacy during aging. The σ1 receptor expression was examined in young (2 months old) and aged (24 months old) C57BL/6 mouse brain using comparative RT-PCR and immunohistochemistry. The pro-mnesic effect of PRE-084, a selective σ1 agonist, was assessed using a water-maze procedure. The σ1 mRNA expression was not affected during aging in the olfactory bulb, hippocampus, hypothalamus, cortex or cerebellum. The σ1 immunolabeling was intense in the olfactory bulb, hippocampus, hypothalamus and midbrain of the young mouse and the distribution appeared unchanged in the aged. The subcellular localization was similar in aged and younger animals, the protein being present on nuclear, mitochondrial, endoplasmic reticular and plasmic membranes. At the behavioral level, aged C57BL/6 mice showed deficits in the invisible platform learning, but not when the platform was visible. Animals subjected to a transfer test under repeated treatment with saline or PRE-084 significantly learned the new platform location. This study shows that σ1 receptor expression is preserved in aged animals and demonstrates the efficacy of a selective σ1 agonist against age-related memory deficits. Targeting this unique receptor may offer an original drug strategy during aging.