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

- The nigrostriatal pathway injury affects the proliferation and activation of glial cells.
- P-ERK was located in glial cells at different time points after brain injury.
- U0126 attenuates p-ERK expression and proliferation and activation of glial cells after injury.
- U0126 improved long-term neurobehavioral function after brain injury.

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 h), but the duration was short (<4 days). According to immunofluorescence double staining, it was found that at 4 and 8 h 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 h; 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.

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