PMID- 25299676 OWN - NLM STAT- MEDLINE DCOM- 20151228 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 10 DP - 2014 TI - Scorpion venom heat-resistant peptide (SVHRP) enhances neurogenesis and neurite outgrowth of immature neurons in adult mice by up-regulating brain-derived neurotrophic factor (BDNF). PG - e109977 LID - 10.1371/journal.pone.0109977 [doi] LID - e109977 AB - Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus martensii Karsch scorpion venom. Although scorpions and their venom have been used in Traditional Chinese Medicine (TCM) to treat chronic neurological disorders, the underlying mechanisms of these treatments remain unknown. We applied SVHRP in vitro and in vivo to understand its effects on the neurogenesis and maturation of adult immature neurons and explore associated molecular mechanisms. SVHRP administration increased the number of 5-bromo-2'-dexoxyuridine (BrdU)-positive cells, BrdU-positive/neuron-specific nuclear protein (NeuN)-positive neurons, and polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive immature neurons in the subventricular zone (SVZ) and subgranular zone (SGZ) of hippocampus. Furthermore immature neurons incubated with SVHRP-pretreated astrocyte-conditioned medium exhibited significantly increased neurite length compared with those incubated with normal astrocyte-conditioned medium. This neurotrophic effect was further confirmed in vivo by detecting an increased average single area and whole area of immature neurons in the SGZ, SVZ and olfactory bulb (OB) in the adult mouse brain. In contrast to normal astrocyte-conditioned medium, higher concentrations of brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) was detected in the conditioned medium of SVHRP-pretreated astrocytes, and blocking BDNF using anti-BDNF antibodies eliminated these SVHRP-dependent neurotrophic effects. In SVHRP treated mouse brain, more glial fibrillary acidic protein (GFAP)-positive cells were detected. Furthermore, immunohistochemistry revealed increased numbers of GFAP/BDNF double-positive cells, which agrees with the observed changes in the culture system. This paper describes novel effects of scorpion venom-originated peptide on the stem cells and suggests the potential therapeutic values of SVHRP. FAU - Wang, Tao AU - Wang T AD - Department of Physiology, Dalian Medical University, Dalian, China; Liaoning Engineering Technology Centre of Target-based Nature Products for Prevention and Treatment of Ageing-related Neurodegeneration, Dalian, China. FAU - Wang, Shi-Wei AU - Wang SW AD - Department of Physiology, Dalian Medical University, Dalian, China; The Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia. FAU - Zhang, Yue AU - Zhang Y AD - Liaoning Engineering Technology Centre of Target-based Nature Products for Prevention and Treatment of Ageing-related Neurodegeneration, Dalian, China. FAU - Wu, Xue-Fei AU - Wu XF AD - Department of Physiology, Dalian Medical University, Dalian, China. FAU - Peng, Yan AU - Peng Y AD - Department of Physiology, Dalian Medical University, Dalian, China. FAU - Cao, Zhen AU - Cao Z AD - Department of Physiology, Dalian Medical University, Dalian, China. FAU - Ge, Bi-Ying AU - Ge BY AD - Liaoning Engineering Technology Centre of Target-based Nature Products for Prevention and Treatment of Ageing-related Neurodegeneration, Dalian, China. FAU - Wang, Xi AU - Wang X AD - Department of Physiology, Dalian Medical University, Dalian, China. FAU - Wu, Qiong AU - Wu Q AD - Department of Physiology, Dalian Medical University, Dalian, China. FAU - Lin, Jin-Tao AU - Lin JT AD - Department of Biotechnology, Dalian Medical University, Dalian, China. FAU - Zhang, Wan-Qin AU - Zhang WQ AD - Department of Physiology, Dalian Medical University, Dalian, China. FAU - Li, Shao AU - Li S AD - Department of Physiology, Dalian Medical University, Dalian, China. FAU - Zhao, Jie AU - Zhao J AD - Department of Physiology, Dalian Medical University, Dalian, China; Liaoning Engineering Technology Centre of Target-based Nature Products for Prevention and Treatment of Ageing-related Neurodegeneration, Dalian, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141009 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Culture Media, Conditioned) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Nerve Tissue Proteins) RN - 0 (Peptides) RN - 0 (Scorpion Venoms) RN - 0 (glial fibrillary astrocytic protein, mouse) RN - 0 (scorpion venom heat-resistant peptide, Buthus martensii) SB - IM MH - Animals MH - Astrocytes/drug effects MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/*biosynthesis MH - Cell Proliferation MH - Culture Media, Conditioned/chemistry MH - Gene Expression Regulation, Developmental/drug effects MH - Glial Fibrillary Acidic Protein MH - Humans MH - Mice MH - Nerve Tissue Proteins/antagonists & inhibitors/*biosynthesis MH - Neurites/drug effects MH - Neurogenesis/*drug effects MH - Neurons/drug effects MH - Peptides/*administration & dosage MH - Scorpion Venoms/*administration & dosage PMC - PMC4192587 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/10/10 06:00 MHDA- 2015/12/29 06:00 PMCR- 2014/10/09 CRDT- 2014/10/10 06:00 PHST- 2014/04/20 00:00 [received] PHST- 2014/09/10 00:00 [accepted] PHST- 2014/10/10 06:00 [entrez] PHST- 2014/10/10 06:00 [pubmed] PHST- 2015/12/29 06:00 [medline] PHST- 2014/10/09 00:00 [pmc-release] AID - PONE-D-14-17740 [pii] AID - 10.1371/journal.pone.0109977 [doi] PST - epublish SO - PLoS One. 2014 Oct 9;9(10):e109977. doi: 10.1371/journal.pone.0109977. eCollection 2014.