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Orexin/Ataxin-3 transgenic mice show increased hypocretin -1-induced G protein activation in the pontine reticular formation


, : Orexin/Ataxin-3 transgenic mice show increased hypocretin -1-induced G protein activation in the pontine reticular formation. FASEB Journal 18(4-5): Abst 394 7

The hypothalamic peptide hcrt modulates arousal and some human narcoleptics have a loss of hcrt neurons (Neuron 27:469, 2000). Tg mice have a selective ablation of hcrt-containing neurons and a narcoleptic-like phenotype (Neuron 30:345, 2001). This study used in vitro (35S)GTP?S autoradiography to test the hypothesis that hcrt-1-induced G protein activation is increased in arousal-related brainstem nuclei of Tg mice. Brainstem sections from 8 wk old male Tg (n=5) and wild type (WT, n=5) mice were assayed for (35S)GTP?S binding (nCi/g) stimulated by hcrt-1 or the ? opioid agonist DAMGO (positive control). Measurements were obtained from PRF, dorsal raphe, lateral and medial parabrachial nuclei, motor trigeminal nucleus, and ventrolateral periaqueductal gray. DAMGO increased G protein activation over basal levels in all 6 nuclei, confirming assay conditions. Comparisons between Tg and WT mice showed that PRF was the only region in which hcrt-1 enhanced G protein activation to a level approaching statistical significance (F=3.0; df=1, 37; p=0.09). Power calculations indicate that only in PRF will statistical significance be achieved with 5 more Tg and WT brains. These data suggest that in response to a loss of hcrt-containing neurons, some hcrt receptors upregulate in the PRF.Support: MH45361, HL40881, HL57120, HL65272, and Dept Anesthesiology. Mice breeding pairs obtained from T. Sakurai.

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