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Treadmill exercise alters the single-nuclei and spatial transcriptional profiles of mouse aging across the neocortex and hippocampus

ABSTRACT: Aging drives a progressive decline in cognition that may be delayed by exercise (Ex). Neocortex (CTX) and hippocampus (HIP) are crucial brain regions for cognition but vulnerable to aging. Whether and how Ex induces changes in molecular and spatial signatures of aging across CTX and HIP remains little known. Herein, we assessed the effects of treadmill Ex against cognitive aging, and characterized the molecular and spatial changes by aging and upon Ex across the CTX and HIP at the single-nuclei resolution. Overall, Ex demonstrated cognitive benefits in old mice and largely protected the brain cells against aging, especially the neurons. Ex regulated the inhibitory neuron-specific aging-associated genes Alcam, Cacna2d3, and Foxp2, rebuilt the cellular communications and distance that were disrupted by aging, and reorganized the spatial distribution of cells across the aging brain, particularly the CTX, which may collectively contribute to the rejuvenation of cognitive function in aged mice. This study provides invaluable insights into Ex-induced benefits against cognitive aging.

ORGANISM(S): Mus musculus

PROVIDER: GSE271563 | GEO | 2025/05/01

REPOSITORIES: GEO

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Project description:Background: Age-related cognitive deficits negatively affect quality of life and can presage serious neurodegenerative disorders. Despite sleep disruption’s well-recognized negative influence on cognition, and its prevalence with age, surprisingly few studies have tested sleep’s relationship to cognitive aging. Methodology: We measured sleep stages in young adult and aged F344 rats during inactive (enhanced sleep) and active (enhanced wake) periods. Animals were behaviorally characterized on the Morris water maze and gene expression profiles of their parietal cortices were taken. Principal Findings: Water maze performance was impaired, and inactive period deep sleep was decreased with age. However, increased deep sleep during the active period was most strongly correlated to maze performance. Transcriptional profiles were strongly associated with behavior and age, and were validated against prior studies. Bioinformatic analysis revealed increased translation and decreased myelin/ neuronal pathways. Conclusions: The F344 rat appears to serve as a reasonable model for some common sleep architecture and cognitive changes seen with age in humans, including the cognitively disrupting influence of active period deep sleep. Microarray analysis suggests that the processes engaged by this sleep are consistent with its function. Thus, active period deep sleep appears temporally misaligned but mechanistically intact, leading to the following: first, aged brain tissue appears capable of generating the slow waves necessary for deep sleep, albeit at a weaker intensity than in young. Second, this activity, presented during the active period, seems disruptive rather than beneficial to cognition. Third, this active period deep sleep may be a cognitively pathologic attempt to recover age-related loss of inactive period deep sleep. Finally, therapeutic strategies aimed at reducing active period deep sleep (e.g., by promoting active period wakefulness and/or inactive period deep sleep) may be highly relevant to cognitive function in the aging community. KEYWORDS: frontal cortex, rat, young or aged We implanted young and aged Fischer 344 rats (n = 6/ group) with wireless EEG, EMG and movement monitoring devices to measure sleep architecture. Animals were trained in the Morris water maze to assess cognitive function, and frontal cortices were removed for microarray analysis.sleep disruption and cognitive decline.

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Treadmill exercise alters the single-nuclei and spatial transcriptional profiles of mouse aging across the neocortex and hippocampus

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