Author Correction: A shared disease-associated oligodendrocyte signature among multiple CNS pathologies

Kenigsbuch, Mor; Bost, Pierre; Halevi, Shahar; Chang, Yuzhou; Chen, Shuo; Ma, Qin; Hajbi, Renana; Schwikowski, Benno; Bodenmiller, Bernd; Fu, Hongjun; Schwartz, Michal; Amit, Ido

doi:10.1038/s41593-023-01266-y

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“…7A). Using prior literature and classical marker genes, we annotated these 15 cell types [37][38][39][40][41][42][43][44][45][46][47][48][49][50] (Fig. 7B).…”

Section: The Glycolysis-related Gene Gapdh Was Downregulated In Hippo...mentioning

confidence: 99%

Neuroinflammation Induces Myelin Damage by Inhibiting Gapdh of Oligodendrocytes in the Hippocampus

Li,

Fu,

Liu

et al. 2024

Preprint

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Background Myelin damage has been detected in central nervous system disease accompanied by neuroinflammation and cognitive dysfunction. However, the mechanism of myelin damage associated with neuroinflammation in the aged brain has not been clarified. Methods We explored the mechanism of myelin damage induced by neuroinflammation in the hippocampus of aged rats through both in vivo and in vitro approaches from the perspective of energy synthesis in oligodendrocytes. We developed a neuroinflammation model by single intraperitoneal injection of LPS and determined cognitive dysfunction and myelin damage in the hippocampus. Single-cell RNA sequencing was employed to exam gene expression changes related to neuroinflammation in oligodendrocytes of the hippocampus and identified Gapdh as a significantly downregulated gene. In vitro, OLN-93 cells were induced to differentiate into mature oligodendrocytes and treated with TNF-α. The effect of Gapdh on TNF-α-induced energy synthesis suppression and MBP reduction in mature oligodendrocytes, and mitochondrial damage, was assessed through Gapdhoverexpression. Results In aged rats, spatial learning and memory impairments were triggered by LPS, alongside neuroinflammatory responses, as evidenced by elevated levels of TNF-α and IL-1β in the hippocampus. Additionally, there was a reduction in myelin protein expression and disorganization within the myelin structure, which was notably thinner in the hippocampus of the LPS-treated group. The proportion of mature oligodendrocyte clusters related to myelination and remyelination decreased, and the expression level of Gapdh significantly decreased in each oligodendrocyte cluster of the LPS group. In vitro, TNF-α induced mature oligodendrocyte apoptosis and reduced GAPDH and MBP expression. The glycolysis and oxidative phosphorylation ability of cells decreased, accompanied by decreased lactate concentration and ATP content. Mitochondrial oxidative stress and damage were also detected. Overexpression of Gapdh improved damage induced by TNF-α. Conclusions Neuroinflammation impairs the energy synthesis functions of glycolysis and oxidative phosphorylation, and mitochondria in mature oligodendrocytes, by inhibiting Gapdh expression. Lack of energy support decreases myelin basic protein levels, subsequently resulting in myelin deterioration, which may lead to cognitive dysfunction.

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“…7A). Using prior literature and classical marker genes, we annotated these 15 cell types [37][38][39][40][41][42][43][44][45][46][47][48][49][50] (Fig. 7B).…”

Section: The Glycolysis-related Gene Gapdh Was Downregulated In Hippo...mentioning

confidence: 99%

Neuroinflammation Induces Myelin Damage by Inhibiting Gapdh of Oligodendrocytes in the Hippocampus

Li,

Fu,

Liu

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Author Correction: A shared disease-associated oligodendrocyte signature among multiple CNS pathologies

Cited by 1 publication

References 0 publications

Neuroinflammation Induces Myelin Damage by Inhibiting Gapdh of Oligodendrocytes in the Hippocampus

Neuroinflammation Induces Myelin Damage by Inhibiting Gapdh of Oligodendrocytes in the Hippocampus

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