Blond McIndoe Laboratories, Manchester Academic Health Science Centre, The University of Manchester, School of Biomedicine, 3.108 Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
J Mol Neurosci. 2013 Feb;49(2):233-43. doi: 10.1007/s12031-012-9813-6. Epub 2012 May 31.
Neurotrophins are a group of polypeptides that specifically influence neuronal activity during development and adult life in the central and peripheral nervous system (PNS). In particular, Schwann cells (SC) in the PNS exert a neurotrophic role following up-regulation of several growth factors, including nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF). Also SC-like cells derived from adipose tissue (dASC), which have molecular and functional properties similar to SC, can produce and secrete NGF and BDNF. Interestingly, gamma-aminobutyric acid (GABA) and its receptors have been also suggested as modulators of development and myelination in PNS. Therefore, it was interesting to investigate whether the stimulation of the GABA-B receptor may regulate the expression of neurotrophins in SC and dASC. Our findings demonstrated that the specific GABA-B receptors agonist baclofen influences the expression and the secretion NGF and BDNF. In particular, 2 and 24 h of baclofen exposure lead to increased neurotrophins expression in both SC and dASC, as measured by western blot. Moreover, enzyme-linked immunosorbent assay showed that also the levels of released neurotrophins were modified after baclofen treatments. The possibility to modulate the neurotrophic potential of adult stem cell, acting on functional GABAergic receptors, could represent a novel pharmacological approach to improve nerve regeneration.
神经营养因子是一组多肽，它们在中枢和周围神经系统（PNS）的发育和成年期特异性地影响神经元活动。特别是 PNS 中的雪旺细胞（SC）在几种生长因子（包括神经生长因子（NGF）和脑源性神经营养因子（BDNF））的上调后发挥神经营养作用。此外，源自脂肪组织的类似 SC 的细胞（dASC）也具有与 SC 相似的分子和功能特性，可以产生和分泌 NGF 和 BDNF。有趣的是，γ-氨基丁酸（GABA）及其受体也被认为是 PNS 发育和髓鞘形成的调节剂。因此，研究 GABA-B 受体的刺激是否可能调节 SC 和 dASC 中神经营养因子的表达是很有趣的。我们的研究结果表明，特异性 GABA-B 受体激动剂巴氯芬影响 NGF 和 BDNF 的表达和分泌。具体而言，巴氯芬暴露 2 和 24 小时后，Western blot 检测到 SC 和 dASC 中神经营养因子的表达增加。此外，酶联免疫吸附试验显示，巴氯芬处理后释放的神经营养因子水平也发生了改变。通过作用于功能性 GABA 能受体来调节成体干细胞的神经营养潜能，可能代表一种改善神经再生的新的药理学方法。
