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.
Highlights
The scorpion Buthus martensii Karsch (BmK) and its venom have long been used in traditional Chinese medicine as drugs for treating chronic neurological diseases, such as epilepsy and cerebral infarction [1]
To determine whether scorpion venom heat-resistant peptide (SVHRP) can increase the number of immature neurons, PSANCAM immunofluorescence staining in the olfactory bulb (OB), subventricular zone (SVZ) and subgranular zone (SGZ) of adult mice was analyzed
These analyses showed that the number of PSA-NCAM-positive cells was significantly increased in the OB, SVZ and SGZ of SVHRP-treated mice (Fig. 2Aa, Ba, Ca, D) compared with untreated adult mice (Fig. 2Ab, Bb, Cb, D) (p, 0.05)
Summary
The scorpion Buthus martensii Karsch (BmK) and its venom have long been used in traditional Chinese medicine as drugs for treating chronic neurological diseases, such as epilepsy and cerebral infarction [1]. It is believed that scorpions and their venom are the effective components. Scorpion venomoriginated peptides exhibit multiple pharmaceutical effects in various physiological and pathological conditions, such as antitumor effects [4], analgesic effects [5] and bradykinin-potentiating, antimicrobial, hemolytic and immune-modulating activities [6]. Our previous work identified one scorpion venom heat-resistant peptide (SVHRP) from BmK venom [7], this peptide exhibits protective effects by inhibiting the excitability of freshly isolated hippocampal neurons [8,9]
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