| Full text | |
| Author(s): Show less - |
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]
Total Authors: 12
|
| Affiliation: | [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
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | Neuropeptides; v. 85, FEB 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
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) | |
| FAPESP's process: | 18/20777-3 - Genetic variants of the Nav 1.5 sodium channel and its therapeutic implications. |
| Grantee: | Julliane Vasconcelos Joviano dos Santos |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |