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Wake-sleep Circuitry and Sleep Disturbances in Neurodegeneration vs. Aging: Is there a difference?

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Event Flyer: 
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James Jackson Putnam Professor
Neurology and Neuroscience
Harvard Medical School
Head of the Department of Neurology
Beth Israel Deaconess Medical Center


Aging is marked by trouble falling asleep, shorter sleep time, sleep fragmentation, and early awakening.  Several neurodegenerative disorders have similar features, but the reason for why aging and neurodegeneration affect wake-sleep is not known.  We have found in individuals with “healthy aging” that their wake-sleep behavior correlates with loss of neurons in brain circuitry that is known to regulate wake-sleep in other species.  In addition, patients with Alzheimer’s disease have much worse cell loss in wake-sleep regulatory neurons, which may account for their aberrant wake-sleep behavior.  We propose that the wake-sleep system may be a sentinel for several neurodegenerative pathologies, with the wake-sleep regulatory neurons being involved and causing the sleep disorder that we call “normal aging” for up to decades before cognitive or motor signs of neurodegeneration appear.


Lim AS, Ellison BA, Wang JL, Yu L, Schenider JA, Buchman AS, Bennett DA, Saper CB.
Sleep is related to neuron numbers in the ventrolateral preoptic/intermediate nucleus in older adults with and without Alzheimer’s disease.
Brain . 2014 Oct;137(Pt 10):2847-61. doi: 10.1093/brain/awu222. Epub 2014 Aug 20.
Machado NLS, Todd WD, Kaur S, Saper CB
Median preoptic GABA and glutamate neurons exert differential control over sleep behavior.
Curr Biol 32:2011-2021. doi: 10.1016/j.cub.2022.03.039
Nardone S, De Luca R, Zito A, Klymko N, Nikoloutsopoulos D, Amsalem O, Brannigan C, Resch JM, Jacobs CL, Pant D, Veregge M, Srinivasan H, Grippo RM, Yang Z, Zeidel ML, Andermann ML, Harris KD, Tsai LT, Arrigoni E, Verstegen AMJ, Saper CB, Lowell BB.
A spatially-resolved transcriptional atlas of the murine dorsal pons at single cell resolution
Nat Commun, 15:1966


Tuesday, April 2, 2024 - 12:30pm


Conference Room: 
Billings Building – Rosedale

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Darlene White