Neuroprotective effect of l-serine against white matter demyelination by harnessing and modulating inflammation in mice. (1st March 2019)

• Record Type: Journal Article
• Authors: Wang, Guohua; Ding, Lingzhi; Gao, Chunyi; Zhang, Nianjiao; Gan, Deqiang; Sun, Yechao; Xu, Lihua; Luo, Qianqian; Jiang, Zhenglin
• Is Part Of: Neuropharmacology. Volume 146(2019)
• Page Start: 39
• Page End: 49
• Publication Date: 2019-03-01
• Subjects: Lysophosphatidylcholine -- l-serine -- Demyelination -- White matter injury -- Microglia; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2018.11.025
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Demyelination in white matter is the end product of numerous pathological processes. This study was designed to evaluate the neuroprotective effect of l -serine and the underlying mechanisms against the demyelinating injury of white matter. A model of focal demyelinating lesions (FDL) was established using the two-point stereotactic injection of 0.25% lysophosphatidylcholine (LPC, 10 μg per point) into the corpus callosum of mice. Mice were then intraperitoneally injected with one of three doses of l -serine (114, 342, or 1026 mg/kg) 2 h after FDL, and then twice daily for the next five days. Behavior tests and histological analysis were assessed for up to twenty-eight days post-FDL induction. Electron microscopy was used for ultrastructural investigation. In vitro, we applied primary co-cultures of microglia and oligodendrocytes for oxygen glucose deprivation (OGD). After establishing FDL, l -serine treatment: 1) improved spatial learning, memory and cognitive ability in mice, and relieved anxiety for 4 weeks post-FDL induction; 2) reduced abnormally dephosphorylated neurofilament proteins, increased myelin basic protein, and preserved anatomic myelinated axons; 3) inhibited microglia activation and reduced the release of inflammatory factors; 4) promoted recruitment and proliferation of oligodendrocyte progenitor cells, and the efficiency of subsequent remyelination on day twenty-eight post-FDL induction. In vitro experiments, showed that l -serine not only directly protected against oligodendrocytes from OGD damage, but also provided an indirect protective effect by regulating microglia. In our study, l -serine offered long-lasting behavioral and oligodendrocyte protection and promoted remyelination. Therefore, l -serine may be an effective clinical treatment aganist white matter injury. Highlights: l -serine has an outstanding therapeutic effect against LPC-induced white matter injury in mice. l -serine offers long-lasting behavioral and oligodendrocyte protection and promotes remyelination. l -serine could provide an additional protective effect by regulating microglia activation.