Abstract
Sonic hedgehog (SHH) as a secreted protein is important for neuronal development in the central nervous system (CNS). However, the mechanism about SHH release remains largely unknown. Here, we showed that SHH was expressed mainly in the synaptic vesicles of hippocampus in both young postnatal and adult rats. High, but not low, frequency stimulation, induces SHH release from the neurons. Moreover, removal of extracellular Ca2+, application of tetrodotoxin (TTX), an inhibitor of voltage-dependent sodium channels, or downregulation of soluble n-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNAREs) proteins, all blocked SHH release from the neurons in response to HFS. Our findings suggest a novel mechanism to control SHH release from the hippocampal neurons.
Highlights
The PTCH1 and SMO have been reported to localize at the synapse of the postnatal and adult hippocampus[7]
We initially examined whether SHH is expressed in the synapse of rat hippocampus at the age of postnatal 20 days (P20) or 2 months old (2-month), on behalf of young postnatal and adult animals, a method similar with previous reports[7]
Analysis of the band densities revealed that SHH expression was enriched in the SYP and post-synaptic density (PSD) fractionations when compared with that in the total lysates (Total) (P = 0.0009 for SYP vs. total, P = 0.008 for PSD vs. total)
Summary
The PTCH1 and SMO have been reported to localize at the synapse of the postnatal and adult hippocampus[7]. It has been reported that enhancing intracellular Ca2+ can induce SHH release in a gastric acid secretion model[8,9]. Exposure to high potassium can increase the amount of SHH protein in the medium of cultured PC6 cells[10]. After confirming the synaptic localization of SHH in the young postnatal and adult hippocampus by synaptosome fractionation, vesicle isolation and immunoelectron microscopy studies, we used cultured hippocampal neurons and acute hippocampal slices to explore whether increase in neuronal activity by electrical stimulation can induce SHH release. We found that electrical stimulation at 100 Hz, but not at 10 Hz, can induce SHH release from the neurons, but not from the astrocytes, in a manner that depends on extracellular Ca2+ and SNAREs proteins
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