Premature aging of the hippocampal neurogenic niche in adult Bmal1‐ deficient mice

Ali, Amira Mohammed; Schwarz-Herzke, Beryl; Stahr, Anna; Prozorovski, Timour; Aktas, Orhan; Gall, Charlotte von

doi:10.18632/aging.100764

Cited by 43 publications

(45 citation statements)

References 73 publications

(107 reference statements)

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“…The identification of proliferating and apoptotic cells as undertaken in the present study extends previous data on neurogenesis (Steiner et al, ; Ali et al, ), gliogenesis (Cameron et al, ; Bondolfi et al, ; Steiner et al, ; Sierra et al, ; Matsumoto et al, ), and angiogenesis (Sierra et al, ), but also on apoptosis of different cell types (Sierra et al, ) in the adult hippocampus. Except for neurons, all other cell types did not display day–night differences in proliferation and apoptosis in the hippocampal subregions investigated.…”

Section: Discussionsupporting

confidence: 87%

Impact of melatonin receptor-signaling on Zeitgeber time-dependent changes in cell proliferation and apoptosis in the adult murine hippocampus

et al. 2017

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The hippocampus is subjected to diurnal/circadian rhythms on both the morphological and molecular levels. Certain aspects of cell proliferation in the adult hippocampus are regulated by melatonin and accompanied by apoptosis to ensure proper tissue maintenance and function. The present study investigated Zeitgeber time (ZT)-dependent changes in cell proliferation and apoptosis in the adult murine hippocampus and their regulation by melatonin receptor type1 and type2 (MT1/2)-mediated signaling. Adult melatonin-proficient C3H/HeN mice and melatonin-proficient (C3H/HeN) mice with targeted deletion of MT1/2 were adapted to a 12-h light, 12-h dark photoperiod and were sacrificed at ZT00, ZT06, ZT12, and ZT18. Immunohistochemistry for Ki67 and activated caspase-3 in combination with different markers for the diverse cell types residing in the hippocampus served to identify and quantify proliferating and apoptotic cells in the hippocampal subregions. ZT-dependent changes in cell proliferation and apoptosis were found exclusively in the subgranular zone (SGZ) and granule cell layer (GCL) of melatonin-proficient mice with functional MT1/2. Cell proliferation in the SGZ showed ZT-dependent changes indicated by an increase of proliferating immature neurons during the dark phase of the 24-h light-dark cycle. Apoptosis showed ZT-dependent changes in the SGZ and GCL indicated by an increase of apoptotic immature neurons at ZT06 (SGZ) and a decrease of immature and mature neurons at ZT18 (GCL). Our results indicate that ZT-dependent changes in proliferation of immature neurons in the SGZ are counterbalanced by ZT-dependent changes in apoptosis of immature and mature neurons in the SGZ and GCL exclusively in mice with functional MT1/2. Therefore, MT1/2-mediated signaling appears to be crucial for generation and timing of ZT-dependent changes in cell proliferation and apoptosis and for differentiation of proliferating cells into neurons in the SGZ. © 2017 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 87%

Impact of melatonin receptor-signaling on Zeitgeber time-dependent changes in cell proliferation and apoptosis in the adult murine hippocampus

et al. 2017

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“…Bmal1 deficient mice develop striking neurological phenotypes, including profound spontaneous astrogliosis, increased oxidative damage, synaptic degeneration, impaired brain functional connectivity (12), impaired learning and memory (60), altered hippocampal neurogenesis (76–78), and lowered seizure threshold (79). In some of these cases, it remains unclear if the phenotype is due to loss of Bmal1 in the cells of the brain itself, or secondary to whole-animal changes in metabolism.…”

Section: Disrupted Cellular Clocks and Neurodegenerationmentioning

confidence: 99%

Mechanisms linking circadian clocks, sleep, and neurodegeneration

Musiek

Holtzman

2016

Science

451

410

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Disruption of normal circadian rhythms and sleep cycles are consequences of aging and can profoundly impact health. Accumulating evidence indicates that circadian and sleep disturbances, which have long been considered symptoms of many neurodegenerative conditions, may actually drive pathogenesis early in the course of these diseases. In this review we explore potential cellular and molecular mechanisms linking circadian dysfunction and sleep loss to neurodegenerative diseases, with a focus on Alzheimer’s Disease. We examine the interplay between central and peripheral circadian rhythms, circadian clock gene function, and sleep in maintaining brain homeostasis, and discuss therapeutic implications. The circadian clock and sleep can influence a number of key processes involved in neurodegeneration, suggesting that these systems might be manipulated to promote healthy brain aging.

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“…The metabolic profiles of the desynchronized young rats were intermediate between control young and old rats, suggesting increased oxidative stress and impaired glucose tolerance due to the desynchronization (Grosbellet et al., ). Mammalian studies have identified correlations between disruption of core oscillator function and acceleration of aging phenotypes (Ali et al., ; Antoch et al., ; Kondratov et al., ; Vinogradova, Anisimov, Bukalev, Semenchenko & Zabezhinski, ). For example, BMAL1 and CLOCK knockout mice have disrupted redox homeostasis, accelerated aging and deficits in cognition (Ali et al., ; Antoch et al., ; Kondratov et al., ).…”

Section: Understanding Circadian and Aging Interactionsmentioning

confidence: 99%

“…Mammalian studies have identified correlations between disruption of core oscillator function and acceleration of aging phenotypes (Ali et al., ; Antoch et al., ; Kondratov et al., ; Vinogradova, Anisimov, Bukalev, Semenchenko & Zabezhinski, ). For example, BMAL1 and CLOCK knockout mice have disrupted redox homeostasis, accelerated aging and deficits in cognition (Ali et al., ; Antoch et al., ; Kondratov et al., ). Similarly, rats housed in constant light exhibit accelerated metabolic pathologies and tumorigenesis and significantly shortened life span (Vinogradova et al., ).…”

Section: Understanding Circadian and Aging Interactionsmentioning

confidence: 99%

Aging and the clock: Perspective from flies to humans

Nobrega

Lyons

2018

Eur J Neurosci

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Endogenous circadian oscillators regulate molecular, cellular and physiological rhythms, synchronizing tissues and organ function to coordinate activity and metabolism with environmental cycles. The technological nature of modern society with round‐the‐clock work schedules and heavy reliance on personal electronics has precipitated a striking increase in the incidence of circadian and sleep disorders. Circadian dysfunction contributes to an increased risk for many diseases and appears to have adverse effects on aging and longevity in animal models. From invertebrate organisms to humans, the function and synchronization of the circadian system weakens with age aggravating the age‐related disorders and pathologies. In this review, we highlight the impacts of circadian dysfunction on aging and longevity and the reciprocal effects of aging on circadian function with examples from Drosophila to humans underscoring the highly conserved nature of these interactions. Additionally, we review the potential for using reinforcement of the circadian system to promote healthy aging and mitigate age‐related pathologies. Advancements in medicine and public health have significantly increased human life span in the past century. With the demographics of countries worldwide shifting to an older population, there is a critical need to understand the factors that shape healthy aging. Drosophila melanogaster, as a model for aging and circadian interactions, has the capacity to facilitate the rapid advancement of research in this area and provide mechanistic insights for targeted investigations in mammals.

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Premature aging of the hippocampal neurogenic niche in adult Bmal1‐ deficient mice

Cited by 43 publications

References 73 publications

Impact of melatonin receptor-signaling on Zeitgeber time-dependent changes in cell proliferation and apoptosis in the adult murine hippocampus

Impact of melatonin receptor-signaling on Zeitgeber time-dependent changes in cell proliferation and apoptosis in the adult murine hippocampus

Mechanisms linking circadian clocks, sleep, and neurodegeneration

Aging and the clock: Perspective from flies to humans

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