Blocking mPTP on Neural Stem Cells and Activating the Nicotinic Acetylcholine Receptor a7 Subunit on Microglia Attenuate Aß-Induced Neurotoxicity on Neural Stem Cells.

Neurochemical research

PubMedID: 26875732

Chen Q, Wang K, Jiang D, Wang Y, Xiao X, Zhu N, Li M, Jia S, Wang Y. Blocking mPTP on Neural Stem Cells and Activating the Nicotinic Acetylcholine Receptor a7 Subunit on Microglia Attenuate Aß-Induced Neurotoxicity on Neural Stem Cells. Neurochem Res. 2016;.
ß-Amyloid (Aß) can stimulate microglia to release a variety of proinflammatory cytokines and induce neurotoxicity. Nicotine has been reported to inhibit TNF-a, IL-1, and ROS production in microglia. Mitochondrial permeability transition pore (mPTP) plays an important role in neurotoxicity as well. Here, we investigated whether activating the microglial a7-nAChR has a neuroprotective role on neural stem cells (NSCs) and the function of mPTP in NSCs in this process. The expression of a7-nAChR in rat NSCs was detected by immunocytochemistry and RT-PCR. The viability of microglia and NSCs was examined by MTT assay. The mitochondrial membrane potential (??m) and morphological characteristics of NSCs was measured by JC-1 staining and transmission electron microscopy respectively. The distribution of cytochrome c in the subcellular regions of NSCs was visualized by confocal laser scanning microscopy, and the expression levels of cyclophilin D and cleaved caspase-3 were assayed by western blot. The apoptotic rate of NSCs was measured by flow cytometry. The expression of a7-nAChR was detected in microglial cells, but no expression was found in NSCs. The viability of rat microglial cells and NSCs was not affected by reagents or coculture itself. Aß1-42-mediated microglial activation impaired the morphology and the ??m of mitochondria of NSCs as well as increased cell apoptosis. However, the damage was attenuated when the a7-nAChRs on microglial cells were activated or the mPTPs on NSCs were blocked. Blockade of mPTPs on NSCs and activation of a7-nAChRs on microglia exhibit neuroprotective roles in Aß-induced neurotoxicity of NSCs.