Rapid down-regulation of tyrosine hydroxylase expression in the olfactory bulb of naris-occluded adult rats.

Abstract

In most sensory systems, afferent innervation regulates morphological and biochemical characteristics of target cells for a limited time during development. Sensory deprivation experiments in adult rats also have suggested a critical period for afferent influences on olfactory bulb structure and function. Previous odorant deprivation studies that employed unilateral naris closure in neonatal rats demonstrated down-regulation of the catecholamine biosynthetic enzyme tyrosine hydroxylase (TH) in dopamine neurons intrinsic to the olfactory bulb. Accompanying the altered biochemical parameters was a decrease in bulb size. To distinguish between deprivation-induced alterations in TH expression secondary to developmental sequelae and those occurring in mature neurons, the consequences of unilateral naris closure were assessed in young adult rats. In agreement with previous studies significant postnatal increases occurred in TH expression and total protein, an indication of bulb size. At 30 days post-closure, total protein was unaltered in the ipsilateral olfactory bulb but showed a small (12.9%), significant decline at 60 days. In contrast to the limited morphological consequences of odor deprivation, profound reductions occurred in TH expression. TH activity ipsilateral to the closure decreased significantly by 14 days post-closure and remained depressed for up to 6 months. In parallel with enzyme activity, TH immunoreactivity did not decline in the first few days post-closure. In situ hybridization revealed that TH mRNA levels decreased rapidly, i.e., by 2 days post-closure, reached a nadir at 1 month, and remained depressed for at least 6 months. The capacity of odor deprivation in the adult rat olfactory system to down-regulate TH expression suggests that this phenotypic alteration occurs independently of a presumed critical period.