Further characterization of the alpha-1 receptor subtype involved in the control of cataplexy in canine narcolepsy. Effects of central alpha-2 adrenergic compounds on canine narcolepsy, a disorder of rapid eye movement sleep. Dopamine D2 mechanisms in canine narcolepsy.
transgenic mouse of a human mutation in a transcriptional repressor (hDEC2-P385R).
Characterized sleep phenotypes of a murine model human short sleeper (i.e.Proposed that narcolepsy may be a unique disease model to study links among fundamental hypothalamic functions in health.Conduct studies of hypocretin replacement therapy in hypocretin-receptor-mutated and ligand-deficient narcoleptic dogs.Reported the histamine deficiency in hypocretin receptor 2-mutated narcoleptic Dobermans, as well as in human narcolepsy and other hypersomnia of central origins.Demonstrated the interaction between the hypocretin and histamine systems and their involvement in sleep regulation.Characterized the diurnal fluctuation of hypocretin-1 in the CSF and extracellular microdialysis perfusates in freely-moving rats and proposed the model for the regulation of wake and sleep by the hypocretin system.These results gave significant insights towards the primary symptoms of narcolepsy. Performed detailed analysis of sleep abnormalities in canine narcolepsy and cataplexy and murine models of narcolepsy.Demonstrated that the midbrain (A9 and A10) and diencephalic (A11) dopaminergic nuclei are involved in the regulation of cataplexy in the canine model.Found that canine narcolepsy displays periodic leg movements during sleep (PLMS), similar to sleep related involuntary movements seen in human PLMS.Identified the presynaptic enhancement of dopaminergic system as the major mode of action of wake-promoting compounds currently available (amphetamine and modafinil).Demonstrated preferential involvement of the adrenergic system for mediating anticataplectic effects of tricyclic antidepressants.adrenergic alpha-1b, alpha-2, dopaminergic D2/3 and cholinergic M2/3 receptor mechanisms) critical for pharmacological control of cataplexy in narcolepsy. Identified the major neurotransmitter systems (i.e.
NARCOLEPSY AND CATAPLEXY IN DOGS SERIES
Our lab contributed to the series of discoveries in the pathophysiology of narcolepsy (see publications presented by the Center for Narcolepsy).
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