Protective effect of a spider recombinant toxin in a murine model of Huntington's disease
Neuropeptides(2021)
摘要
Abnormal calcium influx and glutamatergic excitotoxicity have been extensively associated with neuronal death in Huntington's disease (HD), a genetic movement disorder. Currently, there is no effective treatment for this fatal condition. The neurotoxin Ph alpha 1 beta has demonstrated therapeutic effects as a calcium channel blocker, for example during pain control. However, little is known about its neuroprotective effect in HD. Herein, we investigated if Ph alpha 1 beta is effective in inhibiting neuronal cell death in the BACHD mouse model for HD. We performed intrastriatal injection of Ph alpha 1 beta in WT and BACHD mice. No side effects or unusual behaviors were observed upon Ph alpha 1 beta administration. Using three different motor behavior tests, we observed that injection of the toxin in BACHD mice greatly improved the animals' motor-force as seen in the Wire-hang test, and also the locomotor performance, according to the Open field test. NeuN labeling for mature neuron detection revealed that Ph alpha 1 beta toxin promoted neuronal preservation in the striatum and cortex, when injected locally. Intrastriatal injection of Ph alpha 1 beta was not able to preserve neurons from the spinal cord and also not revert muscle atrophy in BACHD mice. Finally, we observed that Ph alpha 1 beta might, at least in part, exert its protective effect by decreasing L glutamate, measured in cerebrospinal fluid. Our data provide evidence of a novel neuroprotector effect of Ph alpha 1 beta, paving a path for the development of new approaches to treat HD motor symptoms.
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关键词
Huntington's disease,Ph alpha 1 beta,Calcium blocker,L-glutamate,Striatum
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