Regulation and role of ERK phosphorylation in glial cells following a nigrostriatal pathway injury

• Published in: Brain research Vol. 1648; no. Pt A; pp. 90 - 100
• Main Authors: Li, Dan, Tong, Lei, Kawano, Hitoshi, Liu, Nan, Yan, Hong-Jing, Zhao, Liang, Li, Hong-Peng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2016
• Subjects: Animals; Astrocyte; Astrocytes - metabolism; Blotting, Western; Brain Injuries - therapy; Butadienes - pharmacology; Butadienes - therapeutic use; Cell Proliferation - physiology; ERK signal pathway; Extracellular Signal-Regulated MAP Kinases - metabolism; Macrophages - metabolism; Male; MAP Kinase Signaling System - physiology; Mice; Microglia - metabolism; Microglia/macrophage; Neuralgia - drug therapy; Neuroglia - metabolism; Neuroglia - physiology; Neurology; Nigrostriatal pathway injury; Nitriles - pharmacology; Nitriles - therapeutic use; Phosphorylation - physiology; Signal Transduction; U0126; ERK signal pathway; Nigrostriatal pathway injury; astrocyte; U0126; microglia/macrophage; Microglia/macrophage; Astrocyte
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2016.07.008

Abstract This study was undertaken to examine the function of extracellular signal–regulated kinase (ERK) signaling pathway on the proliferation and activation of microglia/macrophage and astrocytes after brain injury in mice. The result of Western blot showed that p-ERK was immediately activated after injury (< 4 hours), but the duration was short (< 4 days). According to immunofluorescence double staining, it was found that at 4 and 8 hours after injury, p-ERK was expressed in microglia/macrophages, and that more cells were co-expressed by p-ERK and IBA-1 (microglia/macrophage marker) at 8 hours; at days 1 and 4, p-ERK was expressed in astrocytes, and more cells were co-expressed by p-ERK and GFAP (astrocyte marker) at day 4. After injury, the mice were injected with U0126 (MAPK/ERK signaling pathway inhibitor) via the femoral vein. Compared with those injected with DMSO, the cell number co-expressed by p-ERK and IBA-1 or GFAP significantly decreased ( P < 0.05). The increase of microglia/macrophage and astrocyte caused by injury was remitted, and the positive cell number significantly decreased ( P < 0.05). Western blot showed that the expression quantity of IBA-1 and GFAP significantly decreased ( P < 0.05). Furthermore, the ERK signaling pathway was involved in the proliferation and activation of the two glial cells types and improved long-term neurobehavioral function after brain injury. Therefore, the exploration of the formation mechanism of glial scar after injury and further research on the therapeutic method of neural regeneration are essential.