Baclofen modulates the expression and release of neurotrophins in schwann-like adipose stem cells.
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.
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. alessandro.faroni@postgrad.manchester.ac.uk
Alessandro
A
Faroni
Francesca
F
Calabrese
Marco Andrea
MA
Riva
Giorgio
G
Terenghi
Valerio
V
Magnaghi
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D058786:GABA-B Receptor Agonists / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D020932:Nerve Growth Factor; D001418:Baclofen