Valproic acid suppresses cuprizone-induced hippocampal demyelination and anxiety-like behavior by promoting cholesterol biosynthesis.
In: Neurobiology of Disease, Jg. 158 (2021-10-01), S. N.PAG
Online
academicJournal
Zugriff:
Myelin consists of several layers of tightly compacted membranes that form an insulating sheath around axons. These membranes are highly enriched in cholesterol, which is essential for the myelination process. Proper myelination is crucial for various neurophysiological functions while demyelination may cause CNS disease, such as multiple sclerosis (MS). Recent studies demonstrated that demyelination occurs not only in the white matter but also in the grey matter, such as the hippocampus, which may cause cognitive deficits and mental disorders. Valproic acid (VPA) is an anticonvulsant agent prescribed for the treatment of epilepsy and seizure. Recently, VPA was reported to alter cholesterol metabolism in neural cells, suggesting that it may play an important role in myelin biogenesis. Here in this study, we found significant demyelination in the hippocampus of the mouse cuprizone model, which is accompanied by reduced cholesterol biosynthesis and increased anxiety-like behavior. VPA treatment, however, suppressed cuprizone-induced hippocampal demyelination and anxiety-like behavior by promoting cholesterol biosynthesis. These data identify an important role of VPA in the hippocampal demyelination process and the hippocampal demyelination-related behavior deficit via regulation of cholesterol biosynthesis, which provides new insights into the mechanisms of VPA as a protective agent against CNS demyelination. • Cuprizone treatment induces hippocampal demyelination and anxiety-like behavior • Cuprizone treatment suppresses hippocampal cholesterol biosynthesis • Valproic acid promotes hippocampal cholesterol biosynthesis in cuprizone-induced demyelination model • Valproic acid protects against cuprizone-induced hippocampal demyelination • Valproic acid suppresses cuprizone-induced anxiety-like behavior [ABSTRACT FROM AUTHOR]
Titel: |
Valproic acid suppresses cuprizone-induced hippocampal demyelination and anxiety-like behavior by promoting cholesterol biosynthesis.
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Autor/in / Beteiligte Person: | Zhu, Xinjian ; Yao, Yuanyuan ; Hu, Yang ; Yang, Jiurong ; Zhang, Canyu ; He, Yuqi ; Zhang, Aifeng ; Liu, Xiufang ; Zhang, Chenchen ; Gan, Guangming |
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Zeitschrift: | Neurobiology of Disease, Jg. 158 (2021-10-01), S. N.PAG |
Veröffentlichung: | 2021 |
Medientyp: | academicJournal |
ISSN: | 0969-9961 (print) |
DOI: | 10.1016/j.nbd.2021.105489 |
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