Defining circadian disruption in neurodegenerative disorders

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

“…This prompts the interest in identifying the mechanisms by which the processes responsible for defining circadian rhythms might simultaneously control the different modifications assessed in this study and certainly others that were not yet investigated. Indeed, although clock genes seem to be able to control mitochondria function ( de Goede et al, 2018 ) as well as synaptic plasticity and memory ( Eckel-Mahan and Storm, 2009 ), it remains to be established if the presently observed loss of circadian variation of synaptic properties and memory is either due to a direct effect of clock genes that are altered in AD ( Sheehan and Musiek, 2020 ) or instead to altered wake-sleep cycles also present in AD ( Colwell, 2021 ) that can affect mitochondria ( Smith and Musiek, 2020 ) as well as synaptic plasticity and memory ( Walker and Stickgold, 2006 ).…”

Hsp40 overexpression in pacemaker neurons delays circadian dysfunction in a Drosophila model of Huntington's disease

“…Circadian disturbances in HD stem from perturbations to the circadian organisation's input, molecular oscillator and output components ( Fifel and Videnovic, 2020 ; Colwell, 2021 ). In R6/2 HD mice, free-running activity rhythms are disrupted, and the SCN molecular oscillations are impaired in vivo , while persisting in organotypic slices, suggesting that the inputs to and outputs from the central clock are affected rather than the molecular clock ( Morton et al, 2005 ; Pallier et al, 2007 ).…”

“…In R6/2 HD mice, free-running activity rhythms are disrupted, and the SCN molecular oscillations are impaired in vivo , while persisting in organotypic slices, suggesting that the inputs to and outputs from the central clock are affected rather than the molecular clock ( Morton et al, 2005 ; Pallier et al, 2007 ). Dysfunctional intrinsically photosensitive retinal ganglion cells, reduction of VIP immunostaining in the SCN, and disrupted rhythms in SCN electrophysiology, cortisol, melatonin, body temperature, heart rate and metabolic outputs ( Smarr et al, 2019 ; Fifel and Videnovic, 2020 ; Colwell, 2021 ) provide evidence for circadian disturbances in HD mice at levels of clock input and output, thus also affecting molecular clockwork in vivo , resulting in overt behavioural and peripheral rhythm disturbances. Although the HD flies used in this study had a subset of their clock neurons targeted, they exhibited a definite circadian disturbance in the overt behavioural rhythms, molecular oscillations, and circadian output neuropeptide Pdf, recapitulating the central clock and circadian output impairments seen in vivo in HD mice.…”

Examination of diurnal variation and sex differences in hippocampal neurophysiology and spatial memory

“…Circadian regulation of physiological processes is advantageous, and dysregulation of circadian rhythms can promote and exacerbate disease onset and symptoms (Logan & McClung, 2019;Colwell, 2021). Therefore, understanding circadian influence on physiology is crucial for designing interventions for diseases with circadian dysfunction, such as neurodegenerative diseases (Lee et al, 2021).…”

“…Tissue-clocks throughout the body are hierarchically organized in a system that drives the timing of 24-h rhythms in physiology and behavior, enabling organisms to adapt to and anticipate regularly occurring events in their environment (Pilorz et al ., 2020; Buijs et al ., 2021). Circadian regulation of physiological processes is advantageous, and dysregulation of circadian rhythms can promote and exacerbate disease onset and symptoms (Logan & McClung, 2019; Colwell, 2021). Therefore, understanding circadian influence on physiology is crucial for designing interventions for diseases with circadian dysfunction, such as neurodegenerative diseases (Lee et al ., 2021).…”