Background:
Brain-Derived Neurotrophic Factor (BDNF) plays critical roles during development
of the central and peripheral nervous systems, as well as in neuronal survival after injury.
Although proBDNF induces neuronal apoptosis after injury in vivo, whether it can also act as a death
factor in vitro and in vivo under physiological conditions and after nerve injury, as well as its mechanism
of inducing apoptosis, is still unclear.
Objective:
In this study, we investigated the mechanisms by which proBDNF causes apoptosis in sensory
neurons and Satellite Glial Cells (SGCs) in Dorsal Root Ganglia (DRG) After Sciatic Nerve
Transection (SNT).
Methods:
SGCs cultures were prepared and a scratch model was established to analyze the role of
proBDNF in sensory neurons and SGCs in DRG following SNT. Following treatment with proBDNF
antiserum, TUNEL and immunohistochemistry staining were used to detect the expression of Glial
Fibrillary Acidic Protein (GFAP) and Calcitonin Gene-Related Peptide (CGRP) in DRG tissue; immunocytochemistry
and Cell Counting Kit-8 (CCK8) assay were used to detect GFAP expression and
cell viability of SGCs, respectively. RT-qPCR, western blot, and ELISA were used to measure mRNA
and protein levels, respectively, of key factors in BDNF-TrkB, proBDNF-p75NTR/sortilin, and apoptosis
signaling pathways.
Results:
proBDNF induced mitochondrial apoptosis of SGCs and neurons by modulating BDNF-TrkB
and proBDNF-p75NTR/sortilin signaling pathways. In addition, neuroprotection was achieved by inhibiting
the biological activity of endogenous proBDNF protein by injection of anti-proBDNF serum. Furthermore,
the anti-proBDNF serum inhibited the activation of SGCs and promoted their proliferation.
Conclusion:
proBDNF induced apoptosis in SGCs and sensory neurons in DRG following SNT. The
proBDNF signaling pathway is a potential novel therapeutic target for reducing sensory neuron and
SGCs loss following peripheral nerve injury.
Sciatic nerve transection triggers release and intercellular transfer of a genetically expressed macromolecular tracer in dorsal root ganglia
