ArticleJournal of neurodevelopmental disorders2022
RCAN1 knockout and overexpression recapitulate an ensemble of rest-activity and circadian disruptions characteristic of Down syndrome, Alzheimer's disease, and normative aging.
Article in Journal of neurodevelopmental disorders, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Restoring RCAN1 dosage mitigates sleep and EEG abnormalities in a Down syndrome model.Neurobiology of disease · 2026Article
- Vertebrate and Invertebrate Animal Models for the Study of Down Syndrome.International journal of molecular sciences · 2025Review
- Neuronal oscillations in cognition: Down syndrome as a model of mouse to human translation.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025Review
- Mapping the hippocampal spatial proteomic signature in male and female mice of an early Alzheimer's disease model.Biology of sex differences · 2025Article
- Calcineurin inhibition may prevent Alzheimer disease in people with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Identification of RCAN1's role in hepatocellular carcinoma using single-cell analysis.BMC cancer · 2024Article
- Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior.Neurobiology of stress · 2024Article
- Targeting CaN/NFAT in Alzheimer's brain degeneration.Frontiers in immunology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRegulator 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 that appear 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.
methodsThe 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 of both sexes.
resultsWe found that daily RCAN1 levels in the hippocampus and suprachiasmatic nucleus (SCN) 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 RCAN1-overexpressing mice displayed lengthened endogenous (free-running) circadian periods like mouse models of AD and aging. In light-entrained young mice, RCAN1 deficiency 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 RCAN1-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. We also found that RCAN1 deficiency but not RCAN1 overexpression altered protein levels of the clock gene Bmal1 in the SCN.
conclusionsCollectively, 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 possibly aging.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.