Dataset Information

Activity-dependent oligodendrocyte calcium dynamics and their changes in Alzheimer's disease.

ABSTRACT: Oligodendrocytes (OCs) form myelin around axons, which is dependent on neuronal activity. This activity-dependent myelination plays a crucial role in training and learning. Previous studies have suggested that neuronal activity regulates proliferation and differentiation of oligodendrocyte precursor cells (OPCs) and myelination. In addition, deficient activity-dependent myelination results in impaired motor learning. However, the functional response of OC responsible for neuronal activity and their pathological changes is not fully elucidated. In this research, we aimed to understand the activity-dependent OC responses and their different properties by observing OCs using in vivo two-photon microscopy. We clarified that the Ca²⁺ activity in OCs is neuronal activity dependent and differentially regulated by neurotransmitters such as glutamate or adenosine triphosphate (ATP). Furthermore, in 5-month-old mice models of Alzheimer's disease, a period before the appearance of behavioral abnormalities, the elevated Ca²⁺ responses in OCs are ATP dependent, suggesting that OCs receive ATP from damaged tissue. We anticipate that our research will help in determining the correct therapeutic strategy for neurodegenerative diseases beyond the synapse.

SUBMITTER: Yoshida K

PROVIDER: S-EPMC10644703 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Activity-dependent oligodendrocyte calcium dynamics and their changes in Alzheimer's disease.

Yoshida Kenji K Kato Daisuke D Sugio Shouta S Takeda Ikuko I Wake Hiroaki H

Frontiers in cellular neuroscience 20231031

Oligodendrocytes (OCs) form myelin around axons, which is dependent on neuronal activity. This activity-dependent myelination plays a crucial role in training and learning. Previous studies have suggested that neuronal activity regulates proliferation and differentiation of oligodendrocyte precursor cells (OPCs) and myelination. In addition, deficient activity-dependent myelination results in impaired motor learning. However, the functional response of OC responsible for neuronal activity and th ...[more]

PMID: 38026691

Similar Datasets

Project description:Alzheimer's disease (AD) is a progressive neurodegenerative dementia with the key pathological hallmark of amyloid deposits that may induce mitochondrial dysfunction. Ginkgolide K (GK) has been proven to have neuroprotective effects. The present study sought to explore the neuroprotective effect of GK through regulation of the expression of mitochondrial Ca2+ uniporter (MCU) in the pathology of AD. SH-SY5Y cells were cultured and the expression of MCU was enhanced by transfection of MCU recombinant vectors or knockdown by MCU small interfering RNA. The cells were treated with GK and amyloid β (Aβ). Thereafter, the effects of GK, MCU expression and Aβ on viability and apoptosis of SH-SY5Y cells were examined via a WST-1 assay, flow cytometry and Caspase-3/8 activity assays, respectively. The effects of GK, MCU expression and Aβ on the calcium levels in mitochondria were also examined. The regulatory effect of GK on MCU expression was examined by reverse transcription-quantitative PCR and western blot analysis. Furthermore, APP/PS1 mice received supplementation with GK and their cognitive ability was then examined through water maze tests, while the expression of MCU was examined using immunohistochemistry. The results indicated that enhancing the expression of MCU inhibited cell viability and promoted apoptosis. GK protected cells from amyloid-induced cytotoxicity by promoting cell viability and preventing cell apoptosis. The neuroprotective effect of GK was abolished when MCU expression was knocked down. GK decreased the expression of MCU in vitro and downregulation of MCU decreased the calcium level in mitochondria. Treatment with GK in APP/PS1 mice downregulated the expression of MCU in the brains and alleviated cognitive impairment. In conclusion, the present study demonstrated that the administration of GK protected neurons by preventing apoptosis. Furthermore, the neuroprotective effect of GK in neuronal cells was indicated to be related to the inhibition of MCU expression. Therefore, administration of GK may be a promising strategy for treating AD.

Project description:Brain connectivity studies have revealed that highly connected 'hub' regions are particularly vulnerable to Alzheimer pathology: they show marked amyloid-β deposition at an early stage. Recently, excessive local neuronal activity has been shown to increase amyloid deposition. In this study we use a computational model to test the hypothesis that hub regions possess the highest level of activity and that hub vulnerability in Alzheimer's disease is due to this feature. Cortical brain regions were modeled as neural masses, each describing the average activity (spike density and spectral power) of a large number of interconnected excitatory and inhibitory neurons. The large-scale network consisted of 78 neural masses, connected according to a human DTI-based cortical topology. Spike density and spectral power were positively correlated with structural and functional node degrees, confirming the high activity of hub regions, also offering a possible explanation for high resting state Default Mode Network activity. 'Activity dependent degeneration' (ADD) was simulated by lowering synaptic strength as a function of the spike density of the main excitatory neurons, and compared to random degeneration. Resulting structural and functional network changes were assessed with graph theoretical analysis. Effects of ADD included oscillatory slowing, loss of spectral power and long-range synchronization, hub vulnerability, and disrupted functional network topology. Observed transient increases in spike density and functional connectivity match reports in Mild Cognitive Impairment (MCI) patients, and may not be compensatory but pathological. In conclusion, the assumption of excessive neuronal activity leading to degeneration provides a possible explanation for hub vulnerability in Alzheimer's disease, supported by the observed relation between connectivity and activity and the reproduction of several neurophysiologic hallmarks. The insight that neuronal activity might play a causal role in Alzheimer's disease can have implications for early detection and interventional strategies.

Dataset Information

Activity-dependent oligodendrocyte calcium dynamics and their changes in Alzheimer's disease.

Publications

Activity-dependent oligodendrocyte calcium dynamics and their changes in Alzheimer's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets