Associate Provost for Research Boston University Medical Campus
NIA - National Institute on Aging	Research Resources

Abstract

Abstract: DESCRIPTION (provided by applicant): The goals of the proposed project are to determine the age-related changes in sleep, temperature regulation, hormonal secretion and morphological integrity of the suprachiasmatic nuclei (SCN) of the hypothalamus in non-human primates and the contribution of melatonin to the maintenance of consolidated nocturnal sleep, thermoregulation and cognitive performance in aged monkeys. Using a lesion-replacement approach, we will also determine the extent to which sleep-promoting and hypothermic effects of melatonin depend on the integrity of the SCN. This will be accomplished by comparing sleep quantity and quality, cognitive performance, the amplitude and temporal patterns of the circadian body rhythms (temperature, hormonal secretion), as well as the effects of melatonin treatment, in old primates to young control animals and young monkeys that receive lesions of the pineal gland (Px), SCN (SCNx) or both pineal and SCN (Px/SCNx). Subjects will be young (5.9 yrs of age) and old (20-24 yrs of age) rhesus monkeys. Five experimental groups (9 monkeys in each group, 45 total) will be tested, including: (1) aged 'operated-on' animals; (2) young adults with Px; (3) young adults with SCNx; (4) young adults with combined Px/SCNx lesions; and (5) young adult 'operated-on' control monkeys. Sleep (polysomnography) and core body temperature will be measured using implanted telemetric probes, activity rhythms will be recorded actigraphically, plasma melatonin and cortisol levels will be measured using radioimmunoassay and cognitive performance will be assessed using neuropsychological tasks. The morphological integrity of the SCN and quality of surgical lesions will be documented using pre- and post-surgery MRI and post-mortem morphological analysis of brain tissue. Comparing different groups of monkeys (old vs. young; old or young vs. Px, SCNx or PxISCNx; Px or SCNx vs. Px/SCNx) and also using within-subject design (comparing measures collected at baseline and after the brain surgery), while documenting morphological integrity of SCN and pineal in each animal, will allow us to determine the contribution of age-related changes in the pineal or SCN to the maintenance of sleep, cognitive functions and circadian body rhythms of temperature and hormonal secretion. This approach will also allow determining the role of melatonin in primate sleep and whether the acute sleep-promoting and hypothermic effects of melatonin are mediated via the SCN.

Thesaurus Terms:
aging, hormone regulation /control mechanism, melatonin, suprachiasmatic nucleus
body temperature regulation, circadian rhythm, cognition, cortisol, eye movement, hypothalamus, pineal body, secretion, sleep
Macaca mulatta, electroencephalography, experimental brain lesion, histopathology, magnetic resonance imaging, neuropsychological test, polysomnography, radioimmunoassay, telemetry

Institution:	BOSTON UNIVERSITY MEDICAL CAMPUS
	715 ALBANY ST, 560
	BOSTON, MA 021182394
Fiscal Year:	2006
Department:	ANATOMY AND NEUROBIOLOGY
Project Start:	30-SEP-2002
Project End:	31-AUG-2007
ICD:	NATIONAL INSTITUTE ON AGING
IRG:	ZRG1