PMID- 28528122 OWN - NLM STAT- MEDLINE DCOM- 20180328 LR - 20220311 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1668 DP - 2017 Aug 1 TI - ProBDNF inhibits proliferation, migration and differentiation of mouse neural stem cells. PG - 46-55 LID - S0006-8993(17)30209-3 [pii] LID - 10.1016/j.brainres.2017.05.013 [doi] AB - ProBDNF, a precursor of brain-derived neurotrophic factor (BDNF), is an important regulator of neurodegeneration, hippocampal long-term depression, and synaptic plasticity. ProBDNF and its receptors pan-neurotrophin receptor p75 (p75NTR), vps10p domain-containing receptor Sortilin and tropomyosin receptor kinase B (TrkB) are expressed in neuronal and glial cells. The role of proBDNF in regulation of neurogenesis is not fully defined. This study aims to uncover the function of proBDNF in regulating the differentiation, migration and proliferation of mouse neural stem cells (NSCs) in vitro. We have found that proBDNF and its receptors are constitutively expressed in NSCs when assessed by immunocytochemistry and western blotting. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay showed that exogenous proBDNF treatment reduced mouse NSCs viability by 38% at 10ng/mL. The migration of NSCs was also reduced by exogenous proBDNF treatment in a concentration-dependent manner (by 90% at 10ng/mL) but increased by anti-proBDNF antibody treatment (by 50%). BrdU (5-Bromo-2'-Deoxyuridine) incorporation was performed for detection of newborn cells. We have found that proBDNF significantly inhibited proliferation of NSCs and reduced the number of differentiated neurons, oligodendrocytes and astrocytes, while anti-proBDNF antibody treatment promoted proliferation and differentiation of NSCs. In conclusion, proBDNF may oppose the functions of mature BDNF by inhibiting the proliferation, differentiation and migration of NSCs during development. Conversely, anti-proBDNF antibody treatment promoted proliferation and differentiation of NSCs. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Li, Jia-Yi AU - Li JY AD - School of Pharmacy and Medical Sciences, Division of Health Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide 5000, SA, Australia. Electronic address: jiayi.li@mymail.unisa.edu.au. FAU - Liu, Jia AU - Liu J AD - Animal Research Centre, Kunming Medical University, Kunming, China. FAU - Manaph, Nimshitha Pavathuparambil Abdul AU - Manaph NPA AD - School of Pharmacy and Medical Sciences, Division of Health Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide 5000, SA, Australia. FAU - Bobrovskaya, Larisa AU - Bobrovskaya L AD - School of Pharmacy and Medical Sciences, Division of Health Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide 5000, SA, Australia. Electronic address: Larisa.Bobrovskaya@unisa.edu.au. FAU - Zhou, Xin-Fu AU - Zhou XF AD - School of Pharmacy and Medical Sciences, Division of Health Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide 5000, SA, Australia. LA - eng PT - Journal Article DEP - 20170517 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Adaptor Proteins, Vesicular Transport) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Protein Precursors) RN - 0 (Receptor, Nerve Growth Factor) RN - Z020Y8WIJ4 (sortilin) SB - IM MH - Adaptor Proteins, Vesicular Transport/pharmacology MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - *Cell Differentiation/drug effects MH - *Cell Movement/drug effects MH - *Cell Proliferation/drug effects MH - Cells, Cultured MH - Hippocampus/drug effects/metabolism MH - Mice, Inbred C57BL MH - Neural Stem Cells/*cytology/drug effects MH - Oligodendroglia/cytology MH - Protein Precursors/metabolism MH - Receptor, Nerve Growth Factor/metabolism OTO - NOTNLM OT - Differentiation OT - Migration OT - Neural stem cell OT - ProBDNF OT - Proliferation EDAT- 2017/05/22 06:00 MHDA- 2018/03/29 06:00 CRDT- 2017/05/22 06:00 PHST- 2016/12/18 00:00 [received] PHST- 2017/04/19 00:00 [revised] PHST- 2017/05/12 00:00 [accepted] PHST- 2017/05/22 06:00 [pubmed] PHST- 2018/03/29 06:00 [medline] PHST- 2017/05/22 06:00 [entrez] AID - S0006-8993(17)30209-3 [pii] AID - 10.1016/j.brainres.2017.05.013 [doi] PST - ppublish SO - Brain Res. 2017 Aug 1;1668:46-55. doi: 10.1016/j.brainres.2017.05.013. Epub 2017 May 17.