Silencing of Activity During Hypoxia Improves Functional Outcomes in Motor Neuron Networks

activity-dependent mechanisms hypoxia longitudinal motor neuron disease multielectrode array (MEA) recording network activity

Journal

Frontiers in integrative neuroscience
ISSN: 1662-5145
Titre abrégé: Front Integr Neurosci
Pays: Switzerland
ID NLM: 101477950

Informations de publication

Date de publication:
2021
Historique:
received: 11 10 2021
accepted: 01 12 2021
entrez: 3 1 2022
pubmed: 4 1 2022
medline: 4 1 2022
Statut: epublish

Résumé

The effects of hypoxia, or reduced oxygen supply, to brain tissue can be disastrous, leading to extensive loss of function. Deoxygenated tissue becomes unable to maintain healthy metabolism, which leads to increased production of reactive oxygen species (ROS) and loss of calcium homoeostasis, with damaging downstream effects. Neurons are a highly energy demanding cell type, and as such they are highly sensitive to reductions in oxygenation and some types of neurons such as motor neurons are even more susceptible to hypoxic damage. In addition to the immediate deleterious effects hypoxia can have on neurons, there can be delayed effects which lead to increased risk of developing neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), even if no immediate consequences are apparent. Furthermore, impairment of the function of various hypoxia-responsive factors has been shown to increase the risk of developing several neurodegenerative disorders. Longitudinal assessment of electrophysiological network activity is underutilised in assessing the effects of hypoxia on neurons and how their activity and communication change over time following a hypoxic challenge. This study utilised multielectrode arrays and motor neuron networks to study the response to hypoxia and the subsequent development of the neuronal activity over time, as well as the effect of silencing network activity during the hypoxic challenge. We found that motor neuron networks exposed to hypoxic challenge exhibited a delayed fluctuation in multiple network activity parameters compared to normoxic networks. Silencing of activity during the hypoxic challenge leads to maintained bursting activity, suggesting that functional outcomes are better maintained in these networks and that there are activity-dependent mechanisms involved in the network damage following hypoxia.

Identifiants

pubmed: 34975426
doi: 10.3389/fnint.2021.792863
pmc: PMC8716921
doi:

Types de publication

Journal Article

Langues

eng

Pagination

792863

Informations de copyright

Copyright © 2021 Fiskum, Sandvig and Sandvig.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Vegard Fiskum (V)

Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.

Axel Sandvig (A)

Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Neurology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
Department of Pharmacology and Clinical Neurosciences, Division of Neuro, Head, and Neck, Umeå University Hospital, Umeå, Sweden.
Department of Community Medicine and Rehabilitation, Umeå University, Umeå, Sweden.

Ioanna Sandvig (I)

Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.

Classifications MeSH