The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia

Swaab, Dick F.; Fliers, Eric; Partiman, T.

doi:10.1016/0006-8993(85)91350-2

Cited by 781 publications

(358 citation statements)

References 33 publications

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“…Our finding of a shorter intrinsic circadian period in women may therefore be attributable, in part, to the higher circulating levels of estrogen in women. Alternatively, it may be that exposure to high estrogen at some point during development alters the hypothalamic circadian pacemaker, leading to the sexual dimorphism that has been reported in suprachiasmatic nucleus structure (40,41). We found that there was no significant interaction between age and sex and that the pre-and postmenopausal women in our study had similar periods, even though the postmenopausal women presumably had lower circulating estrogen levels.…”

Section: Resultssupporting

confidence: 44%

Sex difference in the near-24-hour intrinsic period of the human circadian timing system

Duffy

Cain

Chang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

488

357

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The circadian rhythms of melatonin and body temperature are set to an earlier hour in women than in men, even when the women and men maintain nearly identical and consistent bedtimes and wake times. Moreover, women tend to wake up earlier than men and exhibit a greater preference for morning activities than men. Although the neurobiological mechanism underlying this sex difference in circadian alignment is unknown, multiple studies in nonhuman animals have demonstrated a sex difference in circadian period that could account for such a difference in circadian alignment between women and men. Whether a sex difference in intrinsic circadian period in humans underlies the difference in circadian alignment between men and women is unknown. We analyzed precise estimates of intrinsic circadian period collected from 157 individuals (52 women, 105 men; aged 18-74 y) studied in a month-long inpatient protocol designed to minimize confounding influences on circadian period estimation. Overall, the average intrinsic period of the melatonin and temperature rhythms in this population was very close to 24 h [24.15 ± 0.2 h (24 h 9 min ± 12 min)]. We further found that the intrinsic circadian period was significantly shorter in women [24.09 ± 0.2 h (24 h 5 min ± 12 min)] than in men [24.19 ± 0.2 h (24 h 11 min ± 12 min); P < 0.01] and that a significantly greater proportion of women have intrinsic circadian periods shorter than 24.0 h (35% vs. 14%; P < 0.01). The shorter average intrinsic circadian period observed in women may have implications for understanding sex differences in habitual sleep duration and insomnia prevalence.biological rhythm | gender | phase angle O n average, women go to bed earlier and wake up earlier than men, and they are more likely to rate themselves as morning types than men on standardized questionnaires (1). We recently reported a substantial sex difference in the entrainment of human circadian rhythms, such that the circadian rhythms of melatonin and temperature were entrained to an earlier time relative to the nightly sleep/darkness episode in women compared with men (2). The neurobiological mechanism underlying this sex difference in entrained circadian phase, which may have important implications for sleep quality and daytime alertness in women, remains unknown. Animal studies suggest that such differences in entrainment, technically called a phase angle difference between an endogenous rhythm (e.g., nightly secretion of melatonin) and the 24-h environmental light-dark (and wakesleep cycle) to which the rhythm is synchronized, may be attributable to underlying differences in either the resetting sensitivity to environmental synchronizers or the intrinsic period of the circadian pacemaker(s) driving circadian rhythmicity (3-5). Little is known about sex differences in the sensitivity to photic resetting in humans, and no sex difference in the sensitivity to melatonin suppression by light has been reported in most studies (6)(7)(8). Findings from multiple studies in nonhuman animals have demonstra...

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Section: Resultssupporting

confidence: 44%

Sex difference in the near-24-hour intrinsic period of the human circadian timing system

Duffy

Cain

Chang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

488

357

View full text Add to dashboard Cite

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“…Neuronal loss and classical AD neuropathology have been shown in the SCN 2, 5, 6, 7. A recent longitudinal study also demonstrated a significant loss of neurons in the hypothalamic ventrolateral preoptic nucleus correlated with sleep fragmentation, as documented by actigraphic recordings 72.…”

Section: Discussionmentioning

confidence: 95%

Melanopsin retinal ganglion cell loss in Alzheimer disease

Morgia

Ross‐Cisneros

Koronyo

et al. 2015

Annals of Neurology

329

397

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ObjectiveMelanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer disease (AD). We investigated mRGCs in AD, hypothesizing that they contribute to circadian dysfunction.MethodsWe assessed retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in 21 mild‐moderate AD patients, and in a subgroup of 16 we evaluated rest–activity circadian rhythm by actigraphy. We studied postmortem mRGCs by immunohistochemistry in retinas, and axons in optic nerve cross‐sections of 14 neuropathologically confirmed AD patients. We coimmunostained for retinal amyloid β (Aβ) deposition and melanopsin to locate mRGCs. All AD cohorts were compared with age‐matched controls.ResultsWe demonstrated an age‐related optic neuropathy in AD by OCT, with a significant reduction of RNFL thickness (p = 0.038), more evident in the superior quadrant (p = 0.006). Axonal loss was confirmed in postmortem AD optic nerves. Abnormal circadian function characterized only a subgroup of AD patients. Sleep efficiency was significantly reduced in AD patients (p = 0.001). We also found a significant loss of mRGCs in postmortem AD retinal specimens (p = 0.003) across all ages and abnormal mRGC dendritic morphology and size (p = 0.003). In flat‐mounted AD retinas, Aβ accumulation was remarkably evident inside and around mRGCs.InterpretationWe show variable degrees of rest–activity circadian dysfunction in AD patients. We also demonstrate age‐related loss of optic nerve axons and specifically mRGC loss and pathology in postmortem AD retinal specimens, associated with Aβ deposition. These results all support the concept that mRGC degeneration is a contributor to circadian rhythm dysfunction in AD. ANN NEUROL 2016;79:90–109

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“…Stopa et al (35) evaluated the degenerative changes in the SCN from patients with severe AD and found neuronal loss and tangles, indicating that the SCN is affected by AD, whereas amyloid plaques were only seldom noted in the SCN. Overall SCN volume has been reported to decrease in dementia of the Alzheimer's type (36), and the expression of the neuropeptide vasoactive intestinal polypeptide (VIP) was found to be decreased in the presenile male SCN (37). There is also a loss of rhythmicity of SCN arginine vasopressin (AVP) during aging (38), and in AD this loss of AVP neurons and rhythmicity is accelerated (39,40).…”

Section: Postmortem and Neuropathology Studiesmentioning

confidence: 99%

The Circadian System in Alzheimer’s Disease: Disturbances, Mechanisms, and Opportunities

Coogan

Schutová

Husung

et al. 2013

Biological Psychiatry

148

131

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Alzheimer's disease (AD) is a devastating neurodegenerative condition associated with severe cognitive and behavioral impairments. Circadian rhythms are recurring cycles that display periods of approximately 24 hours and are driven by an endogenous circadian timekeeping system centered on the suprachiasmatic nucleus of the hypothalamus. We review the compelling evidence that circadian rhythms are significantly disturbed in AD and that such disturbance is of significant clinical importance in terms of behavioral symptoms. We also detail findings from neuropathological studies of brain areas associated with the circadian system in postmortem studies, the use of animal models of AD in the investigation of circadian processes, and the evidence that chronotherapeutic approaches aimed at bolstering weakened circadian rhythms in AD produce beneficial outcomes. We argue that further investigation in such areas is warranted and highlight areas for future research that might prove fruitful in ultimately providing new treatment options for this most serious and intractable of conditions.

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The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia

Cited by 781 publications

References 33 publications

Sex difference in the near-24-hour intrinsic period of the human circadian timing system

Sex difference in the near-24-hour intrinsic period of the human circadian timing system

Melanopsin retinal ganglion cell loss in Alzheimer disease

The Circadian System in Alzheimer’s Disease: Disturbances, Mechanisms, and Opportunities

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