Can mild cognitive impairment and Alzheimer’s disease be diagnosed by monitoring a miRNA triad in the blood?

Wei, Zhuang‐Yao D.; Shetty, Ashok K.

doi:10.1111/acel.13627

Cited by 12 publications

(6 citation statements)

References 47 publications

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“…Similarly, some studies indicated that miR-146a-5p was specific to microglia or mainly derived from microglia, and the deletion of miR-146a could affect function and proteome of microglia [ 50 , 51 ]. We know that miR-146a-5p is an inflammation-related miRNA, which plays an indispensable role in regulating the pathology of AD and the development of depression [ 27 , 52 , 53 ]. However, other studies have indicated that miRNA overexpression does not seem to induce cognitive deficits in wild mice [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome

et al. 2023

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Intermittent hypoxia is the best predictor of developing cognitive decline and Alzheimer’s disease progression in patients with obstructive sleep apnea. The nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome has been poorly studied as a regulator of neuroinflammation in cognitive impairment caused by intermittent hypoxia. As critical inflammatory cells, exosomes secreted by microglia have been found to affect the spread of pathologic proteins and neuropathology in neurodegenerative diseases. However, the effects of microglial exosomes on neuroinflammation and cognitive outcomes after intermittent hypoxia remain unclear. In this study, the role of miRNAs in microglial exosomes in improving cognitive deficits in mice exposed to intermittent hypoxia was investigated. We demonstrated that miR-146a-5p fluctuated over time in microglial exosomes of mice exposed to intermittent hypoxia for different periods of time, which could regulate neuronal NLRP3 inflammasome and neuroinflammation. In primary neurons, we found that miR-146a-5p regulated mitochondrial reactive oxygen species by targeting HIF1α, thus affecting the NLRP3 inflammasome and secretion of inflammatory factors. Similarly, further studies showed that inhibition of NLRP3 by administering overexpressed miR-146a-5p in microglial exosomes and MCC950 has improved neuroinflammation and cognitive dysfunction in mice after intermittent hypoxia. In conclusion, NLRP3 inflammasome may be a regulatory target for ameliorating cognitive impairment caused by intermittent hypoxia, and microglial exosomal miR-146a-5p may be a promising therapeutic strategy.

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Section: Discussionmentioning

confidence: 99%

Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome

et al. 2023

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“…Due to this, these patients are more likely to progress and present later with severe forms of cognitive impairment. There is need to support primary healthcare providers in diabetic and hypertensive clinics with mental health training in order to equip them with knowledge and skills to screen and identify dementia in its early stages and initiate the appropriate management strategies and timely referrals to halt and retard progression ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Barriers and facilitators to cognitive impairment screening among older adults with diabetes mellitus and hypertension by primary healthcare providers in rural Uganda

Muwanguzi

Obua

Maling

et al. 2023

Front. Health Serv.

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BackgroundThe burden of non-communicable diseases and cognitive impairment exhibit a linear rise in sub-Saharan Africa due to the increase in life expectancy. Non-communicable diseases like diabetes mellitus and hypertension increase the risk for cognitive impairment. To improve our understanding of the underpinnings of the cognitive impairment screening, this study explored the barriers and facilitators of routine cognitive impairment screening in a primary healthcare setting guided by the Capacity, Opportunity, Motivation Behavioral change (COM-B) model.MethodsThis was a descriptive qualitative study with primary healthcare providers who provide care to older adults with diabetes mellitus and hypertension at three primary healthcare centers in Mbarara district southwestern Uganda. In-depth interviews were conducted using a semi structured interview guide. Interviews were audio-recorded, transcribed verbatim, and analyzed using the framework approach along the COM-B components. Each COM-B component factors were categorized as barriers and facilitators.ResultsWe conducted 20 in-depth interviews with clinical officers, enrolled nurses, and a psychiatric nurse. The questions were guided by the Capacity, Opportunity and Motivation Behavioral change (COM-B) framework to identify barriers and facilitators to cognitive impairment screening. The factors that negatively affected the screening were considered as barriers, while the positive as facilitators. Capacity related barriers to cognitive impairment screening included chronic understaffing, primary healthcare provider non-involvement, lack of training/skills, lack of knowledge and awareness in screening, absence of caretakers, lack of patient awareness of cognitive problems; while facilitators were staff recruitment, primary healthcare provider involvement, and specialized training. Opportunity related barriers to screening included patient overload, infrastructure shortage, and time constraints. Motivation related barriers included lack of screening guidance and policy, while the facilitators were availability of mentorship programs for primary healthcare providers.ConclusionsIntegrating cognitive impairment screening in primary health care requires engagement of relevant stakeholders with the focus on addressing implementation challenges through capacity development. Timely cognitive impairment screening at the first point of care initiates a cascade of interventions for timely enrollment into care, thus arresting the progress of cognitive impairment that leads to dementia.

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“…Their expression and activity are often dysregulated in pathological states resulting in a shift of the cellular and extracellular miRNA patterns. Therefore, miRNA profiling along with the analysis of their target signaling pathways has emerged as a promising approach to study the pathogenesis of many diseases (Chen et al, 2010;Geekiyanage et al, 2012;Bencurova et al, 2017;Paul et al, 2018;Figueiredo et al, 2022;Khan and Saraya, 2022;Wei and Shetty, 2022).…”

Section: Introductionmentioning

confidence: 99%

microRNA-dependent regulation of gene expression in GABAergic interneurons

Kołosowska

Schratt

Winterer

2023

Front. Cell. Neurosci.

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Information processing within neuronal circuits relies on their proper development and a balanced interplay between principal and local inhibitory interneurons within those circuits. Gamma-aminobutyric acid (GABA)ergic inhibitory interneurons are a remarkably heterogeneous population, comprising subclasses based on their morphological, electrophysiological, and molecular features, with differential connectivity and activity patterns. microRNA (miRNA)-dependent post-transcriptional control of gene expression represents an important regulatory mechanism for neuronal development and plasticity. miRNAs are a large group of small non-coding RNAs (21–24 nucleotides) acting as negative regulators of mRNA translation and stability. However, while miRNA-dependent gene regulation in principal neurons has been described heretofore in several studies, an understanding of the role of miRNAs in inhibitory interneurons is only beginning to emerge. Recent research demonstrated that miRNAs are differentially expressed in interneuron subclasses, are vitally important for migration, maturation, and survival of interneurons during embryonic development and are crucial for cognitive function and memory formation. In this review, we discuss recent progress in understanding miRNA-dependent regulation of gene expression in interneuron development and function. We aim to shed light onto mechanisms by which miRNAs in GABAergic interneurons contribute to sculpting neuronal circuits, and how their dysregulation may underlie the emergence of numerous neurodevelopmental and neuropsychiatric disorders.

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Can mild cognitive impairment and Alzheimer’s disease be diagnosed by monitoring a miRNA triad in the blood?

Cited by 12 publications

References 47 publications

Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome

Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome

Barriers and facilitators to cognitive impairment screening among older adults with diabetes mellitus and hypertension by primary healthcare providers in rural Uganda

microRNA-dependent regulation of gene expression in GABAergic interneurons

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