ALTERED NEURONAL-ACTIVITY RHYTHM AND GLUTAMATE-RECEPTOR EXPRESSION INTHE SUPRACHIASMATIC NUCLEI OF TRYPANOSOMA BRUCEI-INFECTED RATS

The parasites Trypanosoma brucei cause African trypanosomiasis (sleepi ng sickness), a severe neuropsychiatric disease with marked disturbanc es of sleep-wake alternation. The sites of brain lesions are not well characterized. The present experimental investigation is focused on th e hypothalamic suprachiasmatic nuclei, which play a role of a biologic al clock entraining endogenous rhythms in the mammalian brain. The ele ctrophysiological properties of these neurons were analyzed in slice p reparations from trypanosome-infected rats The neuronal spontaneous ac tivity, which shows a circadian oscillation, was markedly altered in t he infected animals, displaying a reduced firing rate and phase advanc e of its circadian peak. The direct retinal fibers, which play a pivot al role in entrainment of the circadian pacemaker, displayed a normal density and distribution in the suprachiasmatic nuclei of infected ani mals after intraocular tracer injections in vivo. At the postsynaptic level, immunohistochemistry and Western blotting revealed in the supra chiasmatic nuclei of infected rats a selective decrease of the express ion of glutamate AMPA GluR2/3 and NMDAR1 receptor subunits that gate r etinal afferents. These data disclose an impairment of the neuronal fu nctions in the biological clock in African trypanosomiasis, and may se rve to unravel functional and molecular mechanisms behind endogenous r hythm disturbances.