Hyperexcitable arousal neurons drive sleep instability in old mice, study finds | News Center

The ability to regulate sleep patterns through this targeted pharmacology could lead to the development of new drug treatments for people with age-related sleep disorders, de Lecea said. The potential therapies would also provide an alternative to hypnotics — drugs that are traditionally used to treat insomnia.

The results of the study support the hypothesis that the arousal circuitry, and particularly the hypocretin system in older people, becomes more easily activated with age. About half of men and women ages 65-74 experience boots of wakefulness at night. Meanwhile, it is estimated that 40%-70% of older adults have chronic sleep problems. Healthy older adults who lose out on a good night’s slumber have higher risks of mortality even after controlling for age, gender and other health issues, research shows.

Effects of sleep deprivation

Given that sleep deprivation affects people’s ability to concentrate and retain and retrieve memories, understanding its mechanisms is a critical step toward improving the health and well-being of older people. Studies have found that sleep disruption contributes to cognition decline, more accidents from falls, daytime drowsiness, disease’s disease and a host of nervous-system conditions and cardiovascular diseases. According to research, disrupted sleep and related health issues are also a leading cause of institutionalization among the elderly.

There is something wrong with the brake system of the older hypocretin neurons.

“Currently, sleep problems in older individuals are treated with drugs that make them drowsy, and their effects may generate even more problems,” de Lecea said. “Our results suggest that flupirtine, a non-opioid painkiller, could be optimized and repurposed to treat insomnia and sleep fragmentation in the elderly.”

Other Stanford co-authors of the study are postdoctoral scholars Valentina Martinez Damonte, PhD, Justus M. Kebschull, PhD, Hiroshi Yamaguchi, PhD, Wen-Jie Bian, PhD, and Carolin Purmann, PhD; Reenal Pattni; Gordon X. Wang, PhD, clinical assistant professor of psychiatry and behavioral sciences; Alexander Eckehart Urban, PhD, associate professor of psychiatry and behavioral sciences; Philippe Mourrain, PhD, associate professor of psychiatry and behavioral sciences; and Julie Kauer, PhD, professor of psychiatry and behavioral sciences.

Researchers at the University of North Carolina-Chapel Hill also contributed to the study.

The research was supported by the National Institutes of Health (grants R01AG047671, R01MH116470, R01NS104950, R01DA011289, R01NS106301, K01AG061230, P30EY026877), the Sleep Research Society Foundation, a Scully Family Seed Grant from the Stanford Alzheimer’s Disease Research Center-, and the New York Stem Cell Foundation.


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