Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
Centre for Biological Sciences, University of Southampton, Southampton, UK.
J Neurosci Res. 2021 Sep;99(9):2216-2227. doi: 10.1002/jnr.24856. Epub 2021 May 29.
Oligodendrocyte progenitor cells (OPCs) are responsible for generating oligodendrocytes, the myelinating cells of the CNS. Life-long myelination is promoted by neuronal activity and is essential for neural network plasticity and learning. OPCs are known to contact synapses and it is proposed that neuronal synaptic activity in turn regulates their behavior. To examine this in the adult, we performed unilateral injection of the synaptic blocker botulinum neurotoxin A (BoNT/A) into the hippocampus of adult mice. We confirm BoNT/A cleaves SNAP-25 in the CA1 are of the hippocampus, which has been proven to block neurotransmission. Notably, BoNT/A significantly decreased OPC density and caused their shrinkage, as determined by immunolabeling for the OPC marker NG2. Furthermore, BoNT/A resulted in an overall decrease in the number of OPC processes, as well as a decrease in their lengths and branching frequency. These data indicate that synaptic activity is important for maintaining adult OPC numbers and cellular integrity, which is relevant to pathophysiological scenarios characterized by dysregulation of synaptic activity, such as age-related cognitive decline, Multiple Sclerosis and Alzheimer's disease.
少突胶质前体细胞（OPCs）负责生成少突胶质细胞，后者是中枢神经系统的髓鞘形成细胞。神经元活动促进终生髓鞘形成，对于神经网络可塑性和学习至关重要。已知 OPC 与突触接触，并且有人提出神经元突触活动反过来调节它们的行为。为了在成年动物中研究这一点，我们将突触阻滞剂肉毒杆菌神经毒素 A（BoNT/A）单侧注射到成年小鼠的海马体中。我们证实 BoNT/A 可在海马体的 CA1 区裂解突触相关蛋白 25（SNAP-25），这已被证明可阻断神经传递。值得注意的是，BoNT/A 显著降低了 OPC 密度，并导致其收缩，这可通过 OPC 标志物 NG2 的免疫标记来确定。此外，BoNT/A 导致 OPC 过程的总数总体减少，以及它们的长度和分支频率降低。这些数据表明，突触活动对于维持成年 OPC 数量和细胞完整性很重要，这与突触活动失调为特征的病理生理情况相关，例如与年龄相关的认知能力下降、多发性硬化症和阿尔茨海默病。
