Hypertension-Induced Neurovascular and Cognitive Dysfunction at Single-Cell Resolution DOI

Samantha M. Schaeffer,

Anthony G. Pacholko, Monica M. Santisteban

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

Summary Arterial hypertension is a leading cause of cognitive impairment, attributed to hemodynamic insufficiency, blood-brain barrier disruption, and white matter damage. However, the molecular mechanisms by which affects brain cells remain unclear. Using scRNA-seq in mouse model induced angiotensin II, we mapped neocortical transcriptomic changes before (3 days) after (42 onset neurovascular deficits. Surprisingly, evidence endothelial transport disruption senescence, stalled oligodendrocyte differentiation, interneuronal hypofunction network imbalance emerged just 3 days. By 42 days, when impairment becomes apparent, deficits myelination axonal conduction, as well neuronal mitochondrial dysfunction developed. These findings reveal previously unrecognized early vulnerability cells, interneurons, oligodendrocytes, provide bases for subsequent hypertension. In addition, data constitute valuable resource future mechanistic studies therapeutic target validation.

Language: Английский

Intermittent fasting attenuates CNS inflammaging - rebalancing the transposonome DOI Creative Commons
Mitchell J Cummins, Ethan T Cresswell, Doug W. Smith

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Abstract A hallmark of CNS aging is sterile, chronic, low-grade neuroinflammation. Understanding how the develops chronic inflammation necessary to achieve extended healthspan. Characterisation neuroinflammatory molecular triggers remains limited. Interventions that reduce neuroinflammation and extend health lifespan could be useful in this regard. One such intervention intermittent fasting (IF), but IF impacts insufficiently understood. To address this, we performed deep RNA-sequencing on young, middle-aged, old, mouse regions. Additionally, sequenced spinal cord animals subject adult lifelong IF. We found most differentially expressed genes (DEGs) at middle age were region specific (~ 50–84%), whilst effect weakened 18–72%) old age, suggesting emergence a more general global profile. DEGs from all regions enriched for inflammatory immune ontologies. Surprisingly, SC was aging- neuroinflammation-impacted both ages, with by far highest number DEGs, largest net increase expression transposable elements (TEs), greatest enrichment immune-related ontologies, generally larger increases gene expression. Overall, normal upregulation sensors non-self, DNA/RNA, activation inflammasomes, cGAS-STING1 interferon response genes, across CNS. Whilst still developed an profile SC, average lower ~ 50% compared age-matched controls. IF-specific apparent, also acts separate, potentially targetable, pathways those impacted aging. Expression disease associated microglia, phagocytic exhaustion, STING1, inflammasome decreased Significantly, TE reversed decrease. In summary, find hotspot, attenuates neuroinflammaging rebalancing transposonome.

Language: Английский

Citations

0
Multimodal brain cell atlas across the adult macaque lifespan DOI Creative Commons
Xiao Zhang,

Guangyao Lai,

Xiangyu Guo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

SUMMARY High-throughput single-cell omics of non-human primate tissues present a remarkable opportunity to study brain aging. Here, we introduce transcriptomic and chromatin accessibility landscape 1,985,317 cells from eight regions 13 cynomolgus female monkeys spanning adult lifespan including exceptionally old individuals up 29-years old. This dataset uncovers dynamic molecular changes in critical functions such as synaptic communication axon myelination, exhibiting high degree cell type region specificity. We identify the multicellular networks pons medulla previously unrecognized hotspot for Furthermore, comparative analyses with human neurodegeneration datasets highlight both shared distinct mechanisms contributing aging disease. In addition, uncover transcription factors implicated monkey pinpoint aging-regulated loci linked longevity neurodegeneration. spatiotemporal atlas will advance our understanding its broader implications health

Language: Английский

Citations

0
Enhancing cognitive abilities through transcutaneous auricular vagus nerve stimulation: Findings from prefrontal functional connectivity analysis and virtual brain simulation DOI Creative Commons

Sora An,

Se Jin Oh, Shinhee Noh

et al.

NeuroImage, Journal Year: 2025, Volume and Issue: unknown, P. 121179 - 121179

Published: March 1, 2025

Language: Английский

Citations

0
Hypertension-Induced Neurovascular and Cognitive Dysfunction at Single-Cell Resolution DOI

Samantha M. Schaeffer,

Anthony G. Pacholko, Monica M. Santisteban

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

Summary Arterial hypertension is a leading cause of cognitive impairment, attributed to hemodynamic insufficiency, blood-brain barrier disruption, and white matter damage. However, the molecular mechanisms by which affects brain cells remain unclear. Using scRNA-seq in mouse model induced angiotensin II, we mapped neocortical transcriptomic changes before (3 days) after (42 onset neurovascular deficits. Surprisingly, evidence endothelial transport disruption senescence, stalled oligodendrocyte differentiation, interneuronal hypofunction network imbalance emerged just 3 days. By 42 days, when impairment becomes apparent, deficits myelination axonal conduction, as well neuronal mitochondrial dysfunction developed. These findings reveal previously unrecognized early vulnerability cells, interneurons, oligodendrocytes, provide bases for subsequent hypertension. In addition, data constitute valuable resource future mechanistic studies therapeutic target validation.

Language: Английский

Citations

0