The GABAergic system in Alzheimer’s disease: a systematic review with meta-analysis

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(12), P. 5025 - 5036

Published: July 7, 2023

Language: Английский

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Tau pathology epigenetically remodels the neuron-glial cross-talk in Alzheimer’s disease

Science Advances, Journal Year: 2023, Volume and Issue: 9(16)

Published: April 21, 2023

The neuron-glia cross-talk is critical to brain homeostasis and particularly affected by neurodegenerative diseases. How neurons manipulate the neuron-astrocyte interaction under pathological conditions, such as hyperphosphorylated tau, a hallmark in Alzheimer’s disease (AD), remains elusive. In this study, we identified excessively elevated neuronal expression of adenosine receptor 1 (Adora1 or A1R) 3×Tg mice, MAPT P301L (rTg4510) patients with AD, patient-derived neurons. up-regulation A1R was found be tau pathology dependent posttranscriptionally regulated Mef2c via miR-133a-3p. Rebuilding miR-133a-3p/A1R signal effectively rescued synaptic memory impairments AD mice. Furthermore, promoted release lipocalin 2 (Lcn2) resulted astrocyte activation. Last, silencing Lcn2 mice ameliorated activation restored plasticity learning/memory. Our findings reveal that remodels neuron-glial promotes progression. Approaches targeting modulating signaling pathway might potential therapeutic strategy for AD.

Language: Английский

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The hippocampus associated GABAergic neural network impairment in early-stage of Alzheimer's disease

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 86, P. 101865 - 101865

Published: Jan. 28, 2023

Language: Английский

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The neurotransmitter puzzle of Alzheimer's: Dissecting mechanisms and exploring therapeutic horizons

Brain Research, Journal Year: 2024, Volume and Issue: 1829, P. 148797 - 148797

Published: Feb. 10, 2024

Language: Английский

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Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment

eLife, Journal Year: 2024, Volume and Issue: 12

Published: March 26, 2024

Increased levels of lactate, an end-product glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These in lactate can result decreased brain pH, which has implicated patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed five mouse models schizophrenia, bipolar disorder, and autism, suggesting shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon animal models, leaving its generality across other disease uncertain. Moreover, the association between specific behavioral abnormalities remains unclear. To address gaps, International Brain pH Project Consortium investigated 109 strains/conditions 2294 animals genetic experimental manipulations relevant Systematic analysis revealed increased were common features multiple depression, epilepsy, Alzheimer’s disease, some additional schizophrenia models. While certain autism also exhibited levels, others showed opposite pattern, potentially reflecting subpopulations within spectrum. Furthermore, utilizing large-scale test battery, multivariate cross-validated prediction poor working memory performance was predominantly associated levels. Importantly, confirmed independent cohort Collectively, findings suggest altered could be attributed dysregulated excitation/inhibition balance, may serve transdiagnostic endophenotypes debilitating characterized by cognitive impairment, irrespective their beneficial detrimental nature.

Language: Английский

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Hotspots and trends of microglia in Alzheimer's disease: a bibliometric analysis during 2000–2022

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: Jan. 24, 2024

Abstract Background Alzheimer's disease is one common type of dementia. Numerous studies have suggested a correlation between and inflammation. Microglia mainly participate in the inflammatory response brain. Currently, ample evidence has shown that microglia are closely related to occurrence development disease. Objective We opted for bibliometric analysis comprehensively summarize advancements study disease, aiming provide researchers with current trends future research directions. Methods All articles reviews pertaining from 2000 2022 were downloaded through Web Science Core Collection. The results subjected using VOSviewer 1.6.18 CiteSpace 6.1 R2. Results Overall, 7449 publications included. number was increasing yearly. United States published most publications. Harvard Medical School papers all institutions. Journal Alzheimer’s Disease o f Neuroscience journals commonly cited, respectively. Mt Heneka author highest productivity co-citation. After analysis, keywords neuroinflammation, amyloid-beta, inflammation, neurodegeneration. Gut microbiota, extracellular vesicle, dysfunction meta-analysis hotspots at present stage likely continue. Conclusion NLRP3 inflammasome, TREM2, gut mitochondrial dysfunction, exosomes hotspots. relationship microglia-mediated neuroinflammation been focus trend research.

Language: Английский

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Sleep deprivation drives brain-wide changes in cholinergic presynapse abundance in Drosophila melanogaster

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(13)

Published: March 18, 2024

Sleep is an evolutionarily conserved state that supports brain functions, including synaptic plasticity, in species across the animal kingdom. Here, we examine neuroanatomical and cell-type distribution of presynaptic scaling fly after sleep loss. We previously found loss drives accumulation active zone scaffolding protein Bruchpilot (BRP) within cholinergic Kenyon cells Drosophila melanogaster mushroom body (MB), but not other classes MB neurons. To test whether similar cell type–specific trends plasticity occur broadly brain, used a flp-based genetic reporter to label BRP cholinergic, dopaminergic, GABAergic, or glutamatergic then collected whole-brain confocal image stacks intensity systematically quantify BRP, marker presynapse abundance, 37 neuropil regions central brain. Our results indicate loss, either by overnight (12-h) mechanical stimulation chronic disruption insomniac mutants, elevates synapse abundance while neurons produce neurotransmitters undergoes weaker, if any, changes. Extending deprivation 24 h brain-wide upscaling glutamatergic, other, synapses. Finally, male–male social pairings induce increased excitatory synapses despite male–female eliciting more waking activity, suggesting experience-specific plasticity. Within neurotransmitter class context, changes are domains, indicating rules may apply during acute need alter excitatory–inhibitory balance

Language: Английский

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Bionic Olfactory Synaptic Transistors for Artificial Neuromotor Pathway Construction and Gas Recognition

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(36)

Published: April 22, 2024

Abstract The superior recognition ability and excitatory–inhibitory balance of the olfactory system has important applications in efficient recognition, analysis, processing data. In this study, transistor synaptic devices are prepared utilizing poly‐diketo‐pyrrolopyrrole‐selenophene polymer (PTDPPSe‐5Si) with excellent electrical properties as active layer, dual‐gas pulses applied for first time to simulate excitatory inhibitory behaviors system. Basic successfully simulated, such excitatory/inhibitory postsynaptic currents (EPSC/IPSC), long‐term potentiation/depression (LTP/LTD). regulation biomimetic olfaction is simulated. This working mechanism attributed capture release carriers channel induced by gas's electron‐donating electron‐withdrawing characteristics. neuromotor pathway constructed using key unit, which enables integration information from neurons output motor neurons. A convolutional neural network achieve eight common laboratory gas types concentrations a accuracy over 97%. simulated exhibited device hold significant importance development artificial networks, intelligent frameworks, robots.

Language: Английский

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BACE1-dependent cleavage of GABAA receptor contributes to neural hyperexcitability and disease progression in Alzheimer’s disease

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Heterogeneous brain abnormalities in subjective cognitive decline converge on a common network and their transcriptional signature

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(3)

Published: March 1, 2025

Abstract INTRODUCTION Subjective cognitive decline (SCD) is increasingly recognized as closely related to future Alzheimer's disease (AD). Numerous neuroimaging findings in SCD are inconsistent. We tested whether the various localize a common brain network. METHODS Using novel coordinate network mapping approach, we delineated damage networks that were functionally connected reported findings. then decoded these using microscale transcriptomic and chemo‐architectures psychological processes. RESULTS enrolled 45 studies comprising 2453 patients 3017 healthy controls. The identified largely localized somatosensory (SMN) default mode (DMN). Both robust perturbations of analyzed parameters an independent validation dataset. Neurobiology correlation analyses some key biological pathways neurotransmitters linked networks. DISCUSSION Our reconcile heterogeneous abnormalities provide richer neurobiological underpinning, which has implications for understanding with SCD. Highlights on reconciled framework. SCD‐related functional involves changes DMN, while structural mainly primary sensory areas. genes predominantly enriched processes synaptic structure, calcium ion binding, cellular metabolism. An ALE meta‐analysis was conducted comparison.

Language: Английский

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