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Brain Advance Access published online on March 27, 2008
Brain, doi:10.1093/brain/awn049
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© The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Dorsomedial SCN neuronal subpopulations subserve different functions in human dementia

David G. Harper1,2, Edward G. Stopa3,4, Victoria Kuo-Leblanc3, Ann C. McKee5,6, Kentaro Asayama1,2, Ladislav Volicer5,7, Neil Kowall5,6 and Andrew Satlin1,2

1Geriatric Psychiatry Program, McLean Hospital, Belmont, MA, 2Department of Psychiatry, Harvard Medical School, Boston, MA, 3Department of Pathology, Rhode Island Hospital, Providence, RI, 4Department of Pathology, Brown University School of Medicine, Providence, RI, 5Geriatric Research, Education and Clinical Center, ENRM VA Hospital, Bedford, MA, 6Departments of Pathology and Neurology, Boston University School of Medicine, Boston, MA and 7Department of Psychiatry, University of South Florida, Tampa, FL

Correspondence to: David G. Harper, PhD, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA E-mail: dharper{at}mclean.harvard.edu

The suprachiasmatic nuclei (SCN) are necessary and sufficient for the maintenance of circadian rhythms in primate and other mammalian species. The human dorsomedial SCN contains populations of non-species-specific vasopressin and species-specific neurotensin neurons. We made time-series recordings of core body temperature and locomotor activity in 19 elderly, male, end-stage dementia patients and 8 normal elderly controls. Following the death of the dementia patients, neuropathological diagnostic information and tissue samples from the hypothalamus were obtained. Hypothalamic tissue was also obtained from eight normal control cases that had not had activity or core temperature recordings previously. Core temperature was analysed for parametric, circadian features, and activity was analysed for non-parametric and parametric circadian features. These indices were then correlated with the degree of degeneration seen in the SCN (glia/neuron ratio) and neuronal counts from the dorsomedial SCN (vasopressin, neurotensin). Specific loss of SCN neurotensin neurons was associated with loss of activity and temperature amplitude without increase in activity fragmentation. Loss of SCN vasopressin neurons was associated with increased activity fragmentation but not loss of amplitude. Evidence for a circadian rhythm of vasopressinergic activity was seen in the dementia cases but no evidence was seen for a circadian rhythm in neurotensinergic activity. These results provide evidence that the SCN is necessary for the maintenance of the circadian rhythm in humans, information on the role of neuronal subpopulations in subserving this function and the utility of dementia in elaborating brain–behaviour relationships in the human.

Key Words: circadian rhythm; Alzheimer's disease; vasopressin; neurotensin; neurodegeneration

Abbreviations: GFAP, glial fibrillary acidic protein; RHT, retinohypothalamic tract; SCN, suprachiasmatic nuclei; VIP, vasoactive intestinal peptide

Received August 29, 2007. Revised January 22, 2008. Accepted February 25, 2008.


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