DISTRIBUTION OF THE UNCOUPLING PROTEIN-2 MESSENGER-RNA IN THE MOUSE-BRAIN

The present study was conducted to investigate the brain distribution of the recently cloned uncoupling protein 2 (UCP2). Northern blot anal yses were first carried out to confirm the presence of UCP2 in the bra in. These analyses revealed the brain presence of UCP2 mRNA and the ab sence of the mRNAs encoding uncoupling protein 1 and uncoupling protei n 3. They also demonstrate that UCP2 mRNA expression was abundant in t he hypothalamus and not affected by cold acclimation. In situ hybridiz ation histochemistry was used to determine the brain distribution of t he mRNA encoding UCP2. A markedly intense hybridization signal was fou nd in the hypothalamus, the ventral septal region, the caudal hindbrai n (medulla), the ventricular region, and the cerebellum. A very highly intense hybridization signal was apparent in the suprachiasmatic nucl eus, the medial parvicellular part of the paraventricular hypothalamic nucleus, the arcuate nucleus, the dorsal motor nucleus of the vagus n erve, and the choroid plexus. The specifically localized expression of UCP2 mRNA suggests that this mRNA has a neuronal localization. Neuron al expression was particularly manifest in the nucleus of the horizont al limb of the diagonal band, the submedius thalamic nucleus and the d orsal motor nucleus of the vagus nerve, where agglomerations of the si lver grains delineated individual cells. The role played by UCP2 in th e brain has yet to be fully described, but the pattern of distribution of the transcript suggests that this mitochondrial protein is part of neuronal circuitries controlling neuroendocrine functions, autonomic responses, and the general arousal of the brain. Given the involvement of the proteins from the uncoupling protein's family in the uncouplin g of cellular respiration, it can be argued that UCP2 contributes to t he metabolic rate and thermoregulation of these circuitries. In additi on, by promoting oxygen consumption in the brain, UCP2 could control t he production of reactive oxygen species and thereby influence the pro cess of neural degeneration. J. Comp. Neurol. 397:549-560, 1998. (C) 1 998 Wiley-Liss, Inc.