Protective effect of a spider recombinant toxin in a murine model of Huntington's disease

Autor(es):Mostrar menos -

Joviano-Santos, Julliane V. ^[1] ; Valadao, Priscila A. C. ^[1] ; Magalhaes-Gomes, Matheus P. S. ^{[1, 2]} ; Fernandes, Lorena F. ^[3] ; Diniz, Danuza M. ^[4] ; Machado, Thatiane C. G. ^[1] ; Soares, Kivia B. ^[1] ; Ladeira, Marina S. ^[1] ; Miranda, Aline S. ^[5] ; Massensini, Andre R. ^[3] ; Gomez, Marcus V. ^[4] ; Guatimosim, Cristina ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Minas Gerais, Dept Morfol, Lab Biol Neurotransmissao, Belo Horizonte, MG - Brazil

^[2] Fac Ciencias Med Minas Gerais, FCMMG, Dept Med, Belo Horizonte, MG - Brazil

^[3] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Fisiol & Biofis, Nucleo Neurociencias, Belo Horizonte, MG - Brazil

^[4] IEP Santa Casa, Belo Horizonte, MG - Brazil

^[5] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Morfol, Lab Neurobiol, Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Neuropeptides; v. 85, FEB 2021.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 18/20777-3 - Variantes genéticas do canal para sódio Nav 1.5 e suas consequências terapêuticas
• Beneficiário: Julliane Vasconcelos Joviano dos Santos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado