Ampakine CX614 increases respiratory rate in a mouse model of Parkinson's disease

Autor(es)

Oliveira, Luiz M. ; Severs, Liza ; Moreira, Thiago S. ; Ramirez, Jan-Marino ; Takakura, Ana C.

• Tipo de documento: Artigo Científico
• Fonte: Brain Research; v. 1815, p. 6-pg., 2023-06-13.

Resumo

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra compacta (SNpc). In a mouse model of PD induced by the injection of 6-hydroxydopamine (6-OHDA) into the caudate putamen (CPu) dyspnea events are very common. Neuroanatomical and functional studies show that the number of glutamatergic neurons in the pre-Bo & BULL;tzinger Complex (preBo & BULL;tC) are reduced. We hypothesize that the neuronal loss, and consequently loss of glutamatergic connections in the respiratory network previously investigated, are responsible for the breathing impairment in PD. Here, we tested whether ampakines (CX614), a subgroup of AMPA receptor positive allosteric modulators, could stimulate the respiratory activity in PD-induced animals. CX614 (50 & mu;M) injected intraperitoneally or directly into the preBo & BULL;tC region reduced the irregularity pattern and increased the respiratory rate by 37% or 82%, respectively, in PD-induced animals. CX614 also increased the respiratory frequency in healthy animals. These data suggest that ampakine CX614 could become a tool to restore breathing in PD. (AU)

• Processo FAPESP: 19/09323-3 - Regulação do fluxo sanguíneo na superfície ventrolateral do bulbo em modelo animal de Doença de Parkinson
• Beneficiário: Luiz Marcelo Oliveira Santos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/01236-4 - Efeitos de tratamentos farmacológicos e não farmacológicos nas alterações respiratórias observadas em um modelo murino da Doença de Parkinson
• Beneficiário: Ana Carolina Takakura Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/23376-1 - Núcleo retrotrapezóide, quimiossensibilidade central e automaticidade respiratória
• Beneficiário: Thiago dos Santos Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/12266-6 - Estimulação optogenética dos neurônios do complexo de pre-Bötzinger e o controle da respiração em um modelo murino da doença de Parkinson
• Beneficiário: Luiz Marcelo Oliveira Santos
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado