The tragedy of growing old is not the burden of accumulated years or the imminence of death, but rather the host of senescent changes that so often degrade and enfeeble the most gallant and competent. Of all the various manifestations of senescence, as Hazlitt pointed out in the nineteenth century, """"""""The worst old age is that of the mind"""""""". Unfortunately, there are a multitude of neural processes for which there are no data at all regarding age- determined changes in either structure or function. Sleep is one of the age-afflicted behaviors for which there are no data regarding the basic mechanisms that are at risk in old age. This is of critical importance because not only are all other activities carried out against a background of sleep (or its absence, wakefulness), but also because sleep has been shown to be significantly altered in aged humans and cats. Accordingly, the overall objective of the proposed research is to determine the fashion in which the mechanisms that control sleep, specifically REM sleep, are degraded in old age. We have spent the last 10 years examining, in aged cats, the degradation in motor activity that occurs in old age. We now propose to examine the mechanisms that control REM sleep, which are also involved in the control of motor activity, during this state. A set of preliminary interdisciplinary studies have been performed based on electrophysiological, morphological (light and electron microscopic), immunocytochemical and in situ hybridization techniques in regions of the brain that are essential in the generation and maintenance of REM sleep, specifically the laterodorsal and pedunculo-pontine tegmental nuclei (LDT/PPT), the locus coeruleus, the dorsal raphe nuclei and the nucleus pontis oralis. We have found a host of degradative changes which include the neurofilament and neurotubule systems of the resident neurons, abnormal synapses including pre- and post-synaptic elements, alterations in trophic factors and trophic factor receptors, size changes in cell bodies, unique dendritic inclusions, lipofuscin accumulation and myelin degradation. On the basis of these preliminary studies, we propose to document these and other age-determined changes in REM sleep-related nuclei in old cats. We will also propose hypotheses to explain the data that are obtained, develop models to test these hypotheses and determine the extent to which manipulations may be developed to deal with degradations in sleep processes and the systems that control sleep in old age.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG004307-19
Application #
6509474
Study Section
Special Emphasis Panel (ZRG1-IFCN-3 (01))
Program Officer
Monjan, Andrew A
Project Start
1999-03-01
Project End
2004-02-29
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
19
Fiscal Year
2002
Total Cost
$418,449
Indirect Cost
Name
University of California Los Angeles
Department
Physiology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Xi, Ming Chu; Fung, Simon J; Yamuy, Jack et al. (2003) Hypocretinergic facilitation of synaptic activity of neurons in the nucleus pontis oralis of the cat. Brain Res 976:253-8

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