scholarly journals Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gauri Ang ◽  
Laurence A. Brown ◽  
Shu K. E. Tam ◽  
Kay E. Davies ◽  
Russell G. Foster ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Ampa Receptor ◽  
Short Term Memory ◽  
Wheel Running ◽  
Activity Patterns ◽  
Recognition Task ◽  
Light Sensitivity ◽  
Individual Variability ◽  
Dark Light ◽  
Rest Activity

AbstractDysfunction of the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 subunit and deficits in synaptic plasticity are implicated in schizophrenia and sleep and circadian rhythm disruption. To investigate the role of GluA1 in circadian and sleep behaviour, we used wheel-running, passive-infrared, and video-based home-cage activity monitoring to assess daily rest–activity profiles of GluA1-knockout mice (Gria1−/−). We showed that these mice displayed various circadian abnormalities, including misaligned, fragmented, and more variable rest–activity patterns. In addition, they showed heightened, but transient, behavioural arousal to light→dark and dark→light transitions, as well as attenuated nocturnal-light-induced activity suppression (negative masking). In the hypothalamic suprachiasmatic nuclei (SCN), nocturnal-light-induced cFos signals (a molecular marker of neuronal activity in the preceding ~1–2 h) were attenuated, indicating reduced light sensitivity in the SCN. However, there was no change in the neuroanatomical distribution of expression levels of two neuropeptides―vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP)―differentially expressed in the core (ventromedial) vs. shell (dorsolateral) SCN subregions and both are known to be important for neuronal synchronisation within the SCN and circadian rhythmicity. In the motor cortex (area M1/M2), there was increased inter-individual variability in cFos levels during the evening period, mirroring the increased inter-individual variability in locomotor activity under nocturnal light. Finally, in the spontaneous odour recognition task GluA1 knockouts’ short-term memory was impaired due to enhanced attention to the recently encountered familiar odour. These abnormalities due to altered AMPA-receptor-mediated signalling resemble and may contribute to sleep and circadian rhythm disruption and attentional deficits in different modalities in schizophrenia.

scholarly journals RCAN1 Knockout and Overexpression Recapitulate an Ensemble of Rest-activity and Circadian Disruptions Characteristic of Down Syndrome, Alzheimer’s Disease, and Normative Aging

2021 ◽  
Author(s):  
Helen Wong ◽  
Jordan M. Buck ◽  
Curtis Borski ◽  
Jessica Pafford ◽  
Bailey N. Keller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Wheel Running ◽  
Activity Patterns ◽  
Circadian Activity ◽  
Activity Rhythms ◽  
Free Running ◽  
Rest Activity ◽  
Young Mice

Abstract Background: Regulator of calcineurin 1 (RCAN1) is overexpressed in Down syndrome (DS), but RCAN1 levels are also increased in Alzheimer's disease (AD) and normal aging. AD is highly comorbid among individuals with DS and is characterized in part by progressive neurodegeneration that resembles accelerated aging. Importantly, abnormal RCAN1 levels have been demonstrated to promote memory deficits and pathophysiology symptomatic of DS, AD, and aging. Anomalous diurnal rest-activity patterns and circadian rhythm disruptions are also common in DS, AD, and aging and have been implicated in facilitating age-related cognitive decline and AD progression. However, no prior studies have assessed whether RCAN1 dysregulation may also promote the age-associated alteration of rest-activity profiles and circadian rhythms, which could in turn contribute to neurodegeneration in DS, AD, and aging. Methods: The present study examined the impacts of RCAN1 deficiency and overexpression on the photic entrainment, circadian periodicity, intensity and distribution, diurnal patterning, and circadian rhythmicity of wheel running in young (3-6 months old) and aged (9-14 months old) mice. All data were initially analyzed by multifactorial ANOVA with variables of genotype, age, treatment, and sex considered as dependent variables.Results: We found that daily RCAN1 levels in the hippocampi of light-entrained young mice are generally constant and that balanced RCAN1 expression is necessary for normal circadian locomotor activity rhythms. While the light-entrained diurnal period was unaltered, RCAN1-null and -overexpressing mice displayed lengthened endogenous (free-running) circadian periods like mouse models of AD and aging. In light-entrained young mice, RCAN1 knockout and overexpression also recapitulated the general hypoactivity, diurnal rest-wake pattern fragmentation, and attenuated amplitudes of circadian activity rhythms reported in DS, preclinical and clinical AD, healthily aging individuals, and rodent models thereof. Under constant darkness, RCAN1-null and -overexpressing mice displayed altered locomotor behavior indicating circadian clock dysfunction. Using the Dp(16)1Yey/+ (Dp16) mouse model for DS, which expresses three copies of Rcan1, we found reduced wheel running activity and rhythmicity in both light-entrained and free-running young Dp16 mice like young RCAN1-overexpressing mice. Critically, these diurnal and circadian deficits were rescued in part or entirely by restoring Rcan1 to two copies in Dp16 mice. Conclusions: Collectively, this study's findings suggest that both loss and aberrant gain of RCAN1 precipitate anomalous light-entrained diurnal and circadian activity patterns emblematic of DS, AD, and aging.

Vigilance States: Central Neural Pathways, Neurotransmitters and Neurohormones

2019 ◽  
Vol 19 (1) ◽  
pp. 26-37 ◽  
Author(s):  
Michele Iovino ◽  
Tullio Messana ◽  
Giovanni De Pergola ◽  
Emanuela Iovino ◽  
Edoardo Guastamacchia ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Neural Pathways ◽  
Light Cycle ◽  
Behavioral State ◽  
State Control ◽  
Dark Light ◽  
Concentration Of Ions ◽  
Brainstem Nuclei ◽  
Reticular Activating System ◽  
Plasmatic Concentration

Background and Objective: The sleep-wake cycle is characterized by a circadian rhythm involving neurotransmitters and neurohormones that are released from brainstem nuclei and hypothalamus. The aim of this review is to analyze the role played by central neural pathways, neurotransmitters and neurohormones in the regulation of vigilance states.Method:We analyzed the literature identifying relevant articles dealing with central neural pathways, neurotransmitters and neurohormones involved in the control of wakefulness and sleep.Results:The reticular activating system is the key center in the control of the states of wakefulness and sleep via alertness and hypnogenic centers. Neurotransmitters and neurohormones interplay during the dark-light cycle in order to maintain a normal plasmatic concentration of ions, proteins and peripheral hormones, and behavioral state control.Conclusion:An updated description of pathways, neurotransmitters and neurohormones involved in the regulation of vigilance states has been depicted.

scholarly journals The Emerging Circadian Phenotype of Borderline Personality Disorder: Mechanisms, Opportunities and Future Directions

2021 ◽  
Vol 23 (5) ◽  
Author(s):  
Niall M. McGowan ◽  
Kate E. A. Saunders
Keyword(s):  
Circadian Rhythm ◽  
Borderline Personality Disorder ◽  
Personality Disorder ◽  
Activity Patterns ◽  
Borderline Personality ◽  
Sleep Wake Disorders ◽  
Future Directions ◽  
Pilot Studies ◽  
Substantial Clinical Benefit ◽  
Biological Target

Abstract Purpose of Review We review the recent evidence suggesting that circadian rhythm disturbance is a common unaddressed feature of borderline personality disorder (BPD); amelioration of which may confer substantial clinical benefit. We assess chronobiological BPD studies from a mechanistic and translational perspective and highlight opportunities for the future development of this hypothesis. Recent Findings The emerging circadian phenotype of BPD is characterised by a preponderance of comorbid circadian rhythm sleep-wake disorders, phase delayed and misaligned rest-activity patterns and attenuated amplitudes of usually well-characterised circadian rhythms. Such disturbances may exacerbate symptom severity, and specific maladaptive personality dimensions may produce a liability towards extremes in chronotype. Pilot studies suggest intervention may be beneficial, but development is limited. Summary Endogenous and exogenous circadian rhythm disturbances appear to be common in BPD. The interface between psychiatry and chronobiology has led previously to novel efficacious strategies for the treatment of psychiatric disorders. We believe that better characterisation of the circadian phenotype in BPD will lead to a directed biological target for treatment in a condition where there is a regrettable paucity of accessible therapies.

Disrupted circadian rhythms in VIP- and PHI-deficient mice

2003 ◽  
Vol 285 (5) ◽  
pp. R939-R949 ◽  
Author(s):  
Christopher S. Colwell ◽  
Stephan Michel ◽  
Jason Itri ◽  
Williams Rodriguez ◽  
J. Tam ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Wheel Running ◽  
Activity Rhythm ◽  
Activity Patterns ◽  
Circadian System ◽  
Diurnal Rhythms ◽  
Constant Darkness ◽  
Light Cycle ◽  
Wild Type ◽  
Deficient Mice

The related neuropeptides vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are expressed at high levels in the neurons of the suprachiasmatic nucleus (SCN), but their function in the regulation of circadian rhythms is unknown. To study the role of these peptides on the circadian system in vivo, a new mouse model was developed in which both VIP and PHI genes were disrupted by homologous recombination. In a light-dark cycle, these mice exhibited diurnal rhythms in activity which were largely indistinguishable from wild-type controls. In constant darkness, the VIP/PHI-deficient mice exhibited pronounced abnormalities in their circadian system. The activity patterns started ∼8 h earlier than predicted by the previous light cycle. In addition, lack of VIP/PHI led to a shortened free-running period and a loss of the coherence and precision of the circadian locomotor activity rhythm. In about one-quarter of VIP/PHI mice examined, the wheel-running rhythm became arrhythmic after several weeks in constant darkness. Another striking example of these deficits is seen in the split-activity patterns expressed by the mutant mice when they were exposed to a skeleton photoperiod. In addition, the VIP/PHI-deficient mice exhibited deficits in the response of their circadian system to light. Electrophysiological analysis indicates that VIP enhances inhibitory synaptic transmission within the SCN of wild-type and VIP/PHI-deficient mice. Together, the observations suggest that VIP/PHI peptides are critically involved in both the generation of circadian oscillations as well as the normal synchronization of these rhythms to light.

scholarly journals Rest-activity patterns and falls and fractures in older men

2016 ◽  
Vol 28 (4) ◽  
pp. 1313-1322 ◽  
Author(s):  
Tara S. Rogers ◽  
Terri L. Blackwell ◽  
Nancy E. Lane ◽  
Greg Tranah ◽  
Eric S. Orwoll ◽  
...  
Keyword(s):  
Activity Patterns ◽  
Older Men ◽  
Rest Activity

scholarly journals Zeitgebers and their association with rest-activity patterns

2018 ◽  
Vol 36 (2) ◽  
pp. 203-213 ◽  
Author(s):  
Mirja Quante ◽  
Sara Mariani ◽  
Jia Weng ◽  
Catherine R Marinac ◽  
Emily R Kaplan ◽  
...  
Keyword(s):  
Activity Patterns ◽  
Rest Activity

scholarly journals Sex Differences in Rest-Activity Circadian Rhythm in Patients With Metabolic Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Antonino Mulè ◽  
Eleonora Bruno ◽  
Patrizia Pasanisi ◽  
Letizia Galasso ◽  
Lucia Castelli ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Circadian Rhythm ◽  
Metabolic Diseases ◽  
Activity Level ◽  
Activity Count ◽  
Cross Sectional ◽  
The Metabolic Syndrome ◽  
Parametric Analyses ◽  
Rest Activity

Rest-Activity circadian Rhythm (RAR) can be used as a marker of the circadian timing system. Recent studies investigated the relationship between irregular circadian rhythms and cardiovascular risk factors such as hypertension, obesity, and dyslipidemia. These factors are related to the Metabolic Syndrome (MS), a clustering of metabolic risk factors that increases the risk of several cardiovascular and metabolic diseases. This cross-sectional analysis aimed to explore the RAR characteristics by actigraphy in subjects with MS, particularly in relation to sex and MS parameters, using parametric and non-parametric analyses. Distinguishing the characteristics of RAR based on sex could prove useful as a tool to improve the daily level of activity and set up customized activity programs based on each person’s circadian activity profile. This study showed that female participants exhibited higher values than male participants in the Midline Estimating Statistic of Rhythm (MESOR) (243.3 ± 20.0 vs 197.6 ± 17.9 activity count), Amplitude (184.5 ± 18.5 vs 144.2 ± 17.2 activity count), which measures half of the extent of the rhythmic variation in a cycle, and the most active 10-h period (M10) (379.08 ± 16.43 vs 295.13 ± 12.88 activity count). All these parameters are indicative of a higher daily activity level in women. Female participants also had lower Intradaily Variability (IV) than male participants (0.75 ± 0.03 vs 0.85 ± 0.03 activity count), which indicates a more stable and less fragmented RAR. These preliminary data provide the first experimental evidence of a difference in RAR parameters between male and female people with MS.

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