REGIONAL SPECIFICITY OF THE LONG-TERM REGULATION OF TYROSINE-HYDROXYLASE IN SOME CATECHOLAMINERGIC RAT BRAIN-STEM AREAS .1. INFLUENCE OF LONG-TERM HYPOXIA

The present study was carried out to investigate the influence of long -term hypoxia on tyrosine hydroxylase (TH) protein quantity in some ca techolaminergic rat brainstem areas such as the dorsomedial medulla (D MM), the ventrolateral medulla (VLM) and the locus coeruleus (LC). TH protein quantity was also measured in a dopaminergic structure, the su bstantia nigra (SN). Male Sprague-Dawley rats were exposed to normobar ic hypoxia (10% O2/90% N2) for 3, 7, 14 or 22 days. Controls were kept in normoxia for the same period. This study demonstrates that: (1) 3 days of hypoxia produced a 50% and a 26% increase in the quantity of T H protein in the rostral and caudal LC, respectively; (2) 14 days of h ypoxia produced a 44% increase of TH protein content exclusively in th e caudal part of DMM and a 31% increase in the VLM area; and (3) the s timulus failed to alter the TH protein quantity in the SN. After 14 an d 22 days of hypoxia respectively, the TH protein content in the LC an d DMM returned to the level of controls. To determine whether the incr ease in TH protein quantity could be related to a change in norepineph rine (NE) content, the rate constant of disappearance (k) of NE was me asured in the catecholaminergic areas of intact or chemodenervated rat s submitted to long-term hypoxia. Our results show that hypoxia causes an increase of TH protein quantity within the subpopulations of catec holaminergic areas additionally with an elevation in the NE content. T hese data suggest a selective response of the TH regulation to long-te rm hypoxia within the caudal DMM catecholaminergic area which receives chemosensory inputs.