The synaptic blocker botulinum toxin A decreases the density and complexity of oligodendrocyte precursor cells in the adult mouse hippocampus

Abstract

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.

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“…Indeed, oligodendrocyte precursor cells (OPCs) had diversified potentials due to the ability of modification and transformation to functional oligodendrocytes, in combination with the dynamic changes of OPCs with time, OPCs has a rapid differentiation rate as neural stem cells (Figure 4E). In fact, OPCs in hippocampus interplay with cells that secrete or express neurotrophic factors, kinds of growth factors and small molecular cytokines to promote their own growth and differentiation 17,18 . And then, the communication circos plot of interaction signature was identified, which mainly acted as Apoe‐Sort1 and Psap‐Gpr37l1 ligand‐receptor pairs between type IC spiral ganglion neuron (cluster4) and astrocytes (cluster15) (Figure 4F,G).…”

“…In fact, OPCs in hippocampus interplay with cells that secrete or express neurotrophic factors, kinds of growth factors and small molecular cytokines to promote their own growth and differentiation. 17,18 And then, the communication circos plot of interaction signature was identified, which mainly acted as Apoe-Sort1 and Psap-Gpr37l1 ligand-receptor pairs between type IC spiral ganglion neuron (cluster4) and astrocytes (cluster15) (Figure 4F,G). Shown as above, Apoe is the marker of astrocytes (cluster15) and Sort1 named sortilin-related receptor, LDLR class A repeats-containing, mainly expressed on type IC spiral ganglion neuron (cluster4), which belongs to fibronectin type III domain family and participates in BP of positive regulation of glial cell-derived neurotrophic factor secretion, negative regulation of neuron death, neurogenesis and so on (Table 1).…”