Synaptic silencing affects the density and complexity of oligodendrocyte precursor cells in the adult mouse hippocampus
Synaptic silencing affects the density and complexity of oligodendrocyte precursor cells in the adult mouse hippocampus
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DOI：
10.1101/2020.09.23.309682
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发表时间：
2020-09
期刊：
影响因子：
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通讯作者：
Irene Chacon-De-La-Rocha;Gemma L. Fryatt;Andrea D Rivera;L. Restani;M. Caleo;O. Raineteau;D. Gomez-Nicola;A. Butt
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文献类型：
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作者：
Irene Chacon-De-La-Rocha;Gemma L. Fryatt;Andrea D Rivera;L. Restani;M. Caleo;O. Raineteau;D. Gomez-Nicola;A. Butt
少突胶质细胞祖细胞（OPC）负责产生少突胶质细胞，CNS的髓鞘形成细胞。终生髓鞘形成由神经元活动促进，并且对于神经网络可塑性和学习至关重要。已知OPC接触突触，并且提出神经元突触活性反过来调节OPC增殖和分化。为了在成年小鼠中检验这一点，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中。我们证实BoNT/A切割海马CA 1区的SNAP-25，这已被证明可以阻断神经传递。值得注意的是，通过BoNT/A的突触沉默显著降低了OPC密度并导致其收缩，如通过OPC标记物NG 2的免疫标记所确定的。突触活动的抑制导致OPC过程的数量总体减少，以及它们的长度和分支频率减少。这些数据表明，突触活动是重要的维持成人OPC的数量和细胞的完整性，这是相关的病理情况下，其特征在于减少突触活动。
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 OPC proliferation and differentiation. 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, synaptic silencing by BoNT/A significantly decreased OPC density and caused their shrinkage, as determined by immunolabelling for the OPC marker NG2. Inhibition of synaptic activity 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 pathological scenarios characterized by decreased synaptic activity.