Impact of circadian and diurnal rhythms on cellular metabolic function and neurodegenerative diseases

Lemos

et al. 2022

Front. Aging Neurosci.

Alzheimer’s disease (AD) is characterized by progressive memory deficits accompanied by synaptic and metabolic deficits, namely of mitochondrial function. AD patients also display a disrupted circadian pattern. Thus, we now compared memory performance, synaptic plasticity, and mitochondria function in 24-week-old non-transgenic (non-Tg) and triple transgenic male mice modeling AD (3xTg-AD) at Zeitgeber 04 (ZT-4, inactive phase) and ZT-16 (active phase). Using the Morris water maze test to minimize the influence of circadian-associated locomotor activity, we observed a circadian variation in hippocampus-dependent learning performance in non-Tg mice, which was impaired in 3xTg-AD mice. 3xTg-AD mice also displayed a lack of circadian variation of their performance in the reversal spatial learning task. Additionally, the amplitude of hippocampal long-term potentiation also exhibited a circadian profile in non-Tg mice, which was not observed in 3xTg-AD mice. Moreover, cerebral cortical synaptosomes of non-Tg mice also displayed a circadian variation of FCCP-stimulated oxygen consumption as well as in mitochondrial calcium retention that were blunted in 3xTg-AD mice. In sum, this multidimensional study shows that the ability to maintain a circadian oscillation in brain behavior, synaptic plasticity, and synaptic mitochondria function are simultaneously impaired in 3xTg-AD mice, highlighting the effects of circadian misalignment in AD.

Section: Discussionmentioning

confidence: 99%

Simultaneous Alteration of the Circadian Variation of Memory, Hippocampal Synaptic Plasticity, and Metabolism in a Triple Transgenic Mouse Model of Alzheimer’s Disease

Lemos

et al. 2022

Front. Aging Neurosci.

“…249,250 Studies have examined the relationship between sleep and circadian rhythm disruption in AD as a key clinical feature of patients with AD is the disruption of physiological sleep patterns. 251,252 AD patients are frequently awake at night. 253 In addition, patients with AD show exacerbation of their symptoms in the evening.…”

Section: Relevance and Links To Dementiamentioning

confidence: 99%

“…Among others, metabolism and its circadian regulation 252 are thought to be a potential therapeutic target for dementia. Next to regulation of glucose metabolism and metabolic function reviewed above, polyamine metabolism is among the metabolic pathways under circadian control.…”

Section: Relevance and Links To Dementiamentioning

confidence: 99%

Stroke in the Time of Circadian Medicine

Mergenthaler,

Balami,

Neuhaus

et al. 2024

Circulation Research

Time-of-day significantly influences the severity and incidence of stroke. Evidence has emerged not only for circadian governance over stroke risk factors, but also for important determinants of clinical outcome. In this review, we provide a comprehensive overview of the interplay between chronobiology and cerebrovascular disease. We discuss circadian regulation of pathophysiological mechanisms underlying stroke onset or tolerance as well as in vascular dementia. This includes cell death mechanisms, metabolism, mitochondrial function, and inflammation/immunity. Furthermore, we present clinical evidence supporting the link between disrupted circadian rhythms and increased susceptibility to stroke and dementia. We propose that circadian regulation of biochemical and physiological pathways in the brain increase susceptibility to damage after stroke in sleep and attenuate treatment effectiveness during the active phase. This review underscores the importance of considering circadian biology for understanding the pathology and treatment choice for stroke and vascular dementia and speculates that considering a patient’s chronotype may be an important factor in developing precision treatment following stroke.

“…It should be noted that metabolic variations are not only necessary for the adaptations but they also are required for internal organizations and disease prevention. Moreover, the changes in the amounts of these metabolic variations could be applied for the prediction of disease or the introduction of individual therapeutic methods based on their specific symptoms [ 8 , 9 , 10 , 11 , 12 , 13 ]. On the other hand, rhythmic or non-rhythmic variations could be applied to 3P (prevention, prediction, and personalized) medicine.…”

Section: Introductionmentioning

confidence: 99%

Physiological Rhythms and Biological Variation of Biomolecules: The Road to Personalized Laboratory Medicine

Coşkun

Zarepour

Zarrabi

2023

IJMS

The concentration of biomolecules in living systems shows numerous systematic and random variations. Systematic variations can be classified based on the frequency of variations as ultradian (<24 h), circadian (approximately 24 h), and infradian (>24 h), which are partly predictable. Random biological variations are known as between-subject biological variations that are the variations among the set points of an analyte from different individuals and within-subject biological variation, which is the variation of the analyte around individuals’ set points. The random biological variation cannot be predicted but can be estimated using appropriate measurement and statistical procedures. Physiological rhythms and random biological variation of the analytes could be considered the essential elements of predictive, preventive, and particularly personalized laboratory medicine. This systematic review aims to summarize research that have been done about the types of physiological rhythms, biological variations, and their effects on laboratory tests. We have searched the PubMed and Web of Science databases for biological variation and physiological rhythm articles in English without time restrictions with the terms “Biological variation, Within-subject biological variation, Between-subject biological variation, Physiological rhythms, Ultradian rhythms, Circadian rhythm, Infradian rhythms”. It was concluded that, for effective management of predicting, preventing, and personalizing medicine, which is based on the safe and valid interpretation of patients’ laboratory test results, both physiological rhythms and biological variation of the measurands should be considered simultaneously.