Circadian rhythms in neurodegenerative diseases: Development of innovative therapies

2022-08-05 0 By

This article was originally compiled by brainNews Brain Science World team.Circadian rhythms, controlled by the suprachiasmatic nucleus (SCN), enable humans to adapt to the 24-hour cycle of the Earth’s rotation and adjust physiological functions and behaviors in harmony with changes in the external environment.When circadian balance is disrupted, it negatively affects a person’s quality of life, such as sleep, awakening, cognition, mental function, motor control and metabolic function.Multiple symptoms associated with neurodegenerative diseases such as Parkinson’s disease (PD), Huntington’s disease (HD), Alzheimer’s disease (AD), and frontotemporal dementia (FTD) exhibit diurnal fluctuations that may be related to circadian rhythms.November 10, 2021Malik Nassan and Aleksandar Videnovic of Harvard Medical School published the article “Circadian rhythms in Neurodegenerative” in Nature Reviews NeurologyDisorders, in which we discuss circadian rhythm changes in neurodegenerative diseases and suggest that understanding and exploiting a highly conserved evolutionary system (circadian rhythm) is a potential therapeutic approach to reduce the burden of neurological disorders.Diurnal balance may play an important role in the progression of neurodegenerative diseases, and there is a bidirectional relationship.At night, melatonin is released from PG, and light suppresses its secretion.Anatomically, circadian disruption is driven by SCN and its afferent and efferent pathways by disease-specific pathological components such as alpha-synuclein, Aβ plaques, and Tau proteins, and circadian disruption may be A risk factor for the progression of neurodegenerative disease.1. Healthy aging of circadian rhythm in Parkinson’s disease is associated with a decrease in the number of endogenous photosensitive retinal ganglion cells (ipRGCs) and the degree of dendrites, and the transmission of light information through the retinosin-hypothalamic tract to the suprchiasmatic nucleus has a negative effect.In PD, SCN and PVN may play an important role in the circadian rhythm of abnormal blood pressure.Studies have shown that ipRGCs density and plexus complexity are reduced in PD patients.Extensive neuropathological changes associated with PD may disrupt the complex network of coordinated signals in this brain region, leading to circadian rhythms out of sync.There is a strong bidirectional relationship between dopamine metabolism and diurnal dynamic balance.In addition, inflammation and oxidative stress, recognized mechanisms associated with PD-specific neurodegeneration, are also influenced by circadian rhythms.Despite increasing evidence of changes in PD’s diurnal dynamic balance, the causal relationship between PD and diurnal function remains inconclusive.Functional indicators of circadian rhythm disruption include sleep-wake disturbance cycle interruption, autonomic nervous failure, ambulatory blood pressure, heart rate variability (HRV), etc.In addition, endogenous circadian rhythms can also be studied by analyzing indicators such as melatonin and cortisol levels, fluctuations in core body temperature, and changes in clock gene expression.Rapidly advancing imaging techniques are also contributing to the ability to assess the structural and functional integrity of the circadian network in patients with Parkinson’s disease.Circadian rhythm-based behavioral interventions have the potential to improve the cognitive abilities of PD patients and may slow disease progression.FIG. 2 Relationship between circadian rhythm and sleep disorders and neurodegenerative diseases 2. Circadian rhythm in Alzheimer’s Disease Common functional indicators of AD circadian rhythm disorders include rest-activity rhythm, core body temperature, and fractal analysis.In preclinical PATIENTS with AD, it appears that higher levels of Aβ deposition are associated with poorer sleep quality.Other indicators of circadian rhythm changes derived from activity recorders in AD patients include increased fragmentation of the rest-activity cycle, increased nocturnal activity, and decreased circadian rhythm amplitude, which can be used to assess the severity of AD.Middle-aged progeny of late-onset AD individuals show phase delays in core body temperature.Increased daytime core body temperature in AD patients has been reported to be associated with increased daytime sleepiness.In longitudinal clinical studies, the inclusion of multiple markers of circadian function from the initial stage of high-risk patients to the stages of MCI and AD dementia could improve the understanding of circadian homeostasis changes in PATIENTS with AD.Conclusion The authors suggest that future research should determine whether circadian rhythm changes accelerate the progression of neurodegenerative diseases and how neurotransmitters affect circadian rhythms in brain regions associated with neurodegenerative diseases.To explore information on circadian disturbances and progression of neurological manifestations in asymptomatic carriers of genetic variants associated with neurodegenerative diseases and/or circadian disturbances.In animal models, manipulation of circadian systems at the molecular and behavioral levels provides insights into the mechanisms of circadian disruption to guide treatment.Circadian rhythm-based interventions such as timed light exposure, timed physical activity and melatonin may improve some symptoms of neurodegenerative disease and may influence the progression of neurodegenerative disease by restoring circadian stability.In addition, optimize existing therapies and explore phototherapy “dosing” (frequency, duration, time and wavelength characteristics).Develop innovative phototherapy technology platforms to provide treatment options to a broader patient population.Nassan, M. & AMP;Videnovic, A. (2022). Circadian rhythms in neurodegenerative disorders. Nature reviews. Neurology, 18(1), 7-24. https://doi.org/10.1038/s41582-021-00577-7 compile author: banana milk (brainnews creative team) school review: the wu is empty (brainnews newsroom)