Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm

Maiese, Kenneth

doi:10.52586/4971

Cited by 17 publications

References 258 publications

(421 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

Circadian regulation of hippocampal function is disrupted with corticosteroid treatment

Birnie

Claydon

Troy

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Disrupted circadian activity is associated with many neuropsychiatric disorders. A major coordinator of circadian biological systems is adrenal glucocorticoid secretion which exhibits a pronounced preawakening peak that regulates metabolic, immune, and cardiovascular processes, as well as mood and cognitive function. Loss of this circadian rhythm during corticosteroid therapy is often associated with memory impairment. Surprisingly, the mechanisms that underlie this deficit are not understood. In this study, in rats, we report that circadian regulation of the hippocampal transcriptome integrates crucial functional networks that link corticosteroid-inducible gene regulation to synaptic plasticity processes via an intrahippocampal circadian transcriptional clock. Further, these circadian hippocampal functions were significantly impacted by corticosteroid treatment delivered in a 5-d oral dosing treatment protocol. Rhythmic expression of the hippocampal transcriptome, as well as the circadian regulation of synaptic plasticity, was misaligned with the natural light/dark circadian-entraining cues, resulting in memory impairment in hippocampal-dependent behavior. These findings provide mechanistic insights into how the transcriptional clock machinery within the hippocampus is influenced by corticosteroid exposure, leading to adverse effects on critical hippocampal functions, as well as identifying a molecular basis for memory deficits in patients treated with long-acting synthetic corticosteroids.

show abstract

Circadian regulation of hippocampal function is disrupted with corticosteroid treatment

Birnie

Claydon

Troy

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

Alterations in protein kinase networks in astrocytes and neurons derived from patients with familial Alzheimer’s Disease

Henkel

Joyce

Shedroff

et al. 2022

Preprint

View full text Add to dashboard Cite

Neurons and astrocytes derived from Alzheimers Disease (AD) patient induced pluripotent stem cells are an evolving technology used to study the pathogenesis and etiology of AD. As the utility of mouse models of AD are increasingly coming into questions, using iPSC technology may offer an opportunity to study this disease with human substrates. Herein, we using a hypothesis generating platform, the PamGene12 Kinome Array, to identify core protein kinases in neurons and astrocytes derived from familial AD patient iPSCs. We identified five core protein kinases in these cells and examined the pathways in which they are enriched. Importantly, we complement our findings using an in-silico approach with postmortem AD brain datasets. While these protein kinases have been conceptualized in the context of traditional AD pathology, they have not been explored in the context of aberrant signaling in the pathophysiology of the disease.

show abstract

Circadian rhythm disruption in critically ill patients

Felten

Dame²,

Lachmann

et al. 2023

Acta Physiologica

View full text Add to dashboard Cite

Patients admitted to the intensive care unit (ICU) are in need of continuous organ replacement strategies and specialized care, for example because of neurological dysfunction, cardio‐pulmonary instability, liver or kidney failure, trauma, hemorrhagic or septic shock or even preterm birth. The 24‐h nursing and care interventions provided to critically ill patients significantly limit resting and/or recovery phases. Consecutively, the patient's endogenous circadian rhythms are misaligned and disrupted, which in turn may interfere with their critical condition. A more thorough understanding of the complex interactions of circadian effectors and tissue‐specific molecular clocks could therefore serve as potential means for enhancing personalized treatment in critically ill patients, conceivably restoring their circadian network and thus accelerating their physical and neurocognitive recovery. This review addresses the overarching issue of how circadian rhythms are affected and disturbed in critically ill newborns and adults in the ICU, and whether the conflicting external or environmental cues in the ICU environment further promote disruption and thus severity of illness. We direct special attention to the influence of cell‐type specific molecular clocks on with severity of organ dysfunctions such as severity of brain dysfunction, pneumonia‐ or ventilator‐associated lung inflammation, cardiovascular instability, liver and kidney failure, trauma, and septic shock. Finally, we address the potential of circadian rhythm stabilization to enhance and accelerate clinical recovery.

show abstract

Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm

Cited by 17 publications

References 258 publications

Circadian regulation of hippocampal function is disrupted with corticosteroid treatment

Circadian regulation of hippocampal function is disrupted with corticosteroid treatment

Alterations in protein kinase networks in astrocytes and neurons derived from patients with familial Alzheimer’s Disease

Circadian rhythm disruption in critically ill patients

Contact Info

Product

Resources

About