title: 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).
abstract: 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.
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Physiology, Dalian Medical University, Dalian, China; The Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia.
authors.forename: Shi-Wei
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Liaoning Engineering Technology Centre of Target-based Nature Products for Prevention and Treatment of Ageing-related Neurodegeneration, Dalian, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Dalian Medical University, Dalian, China.
authors.forename: Xue-Fei
authors.initials: XF
authors.lastname: Wu
authors.affiliation: Department of Physiology, Dalian Medical University, Dalian, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Physiology, Dalian Medical University, Dalian, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Liaoning Engineering Technology Centre of Target-based Nature Products for Prevention and Treatment of Ageing-related Neurodegeneration, Dalian, China.
authors.forename: Bi-Ying
authors.initials: BY
authors.lastname: Ge
authors.affiliation: Department of Physiology, Dalian Medical University, Dalian, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Physiology, Dalian Medical University, Dalian, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, China.
authors.forename: Jin-Tao
authors.initials: JT
authors.lastname: Lin
authors.affiliation: Department of Physiology, Dalian Medical University, Dalian, China.
authors.forename: Wan-Qin
authors.initials: WQ
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Dalian Medical University, Dalian, China.
authors.forename: Shao
authors.initials: S
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D049109:Cell Proliferation; D017077:Culture Media, Conditioned / Q000737:chemistry; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016501:Neurites / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage*; D012604:Scorpion Venoms / Q000008:administration & dosage*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017077:Culture Media, Conditioned; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D010455:Peptides; D012604:Scorpion Venoms; C528900:glial fibrillary astrocytic protein, mouse; C000603756:scorpion venom heat-resistant peptide, Buthus martensii