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

Author(s)

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

• Document type: Journal article
• Source: Brain Research; v. 1815, p. 6-pg., 2023-06-13.

Abstract

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)

• FAPESP's process: 19/09323-3 - Regulation of blood flow in the ventrolateral surface of the medulla in animal a model of Parkinson's disease
• Grantee: Luiz Marcelo Oliveira Santos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/01236-4 - Effects of pharmacological and non-pharmacological treatments on respiratory changes observed in a murine model of Parkinson's disease
• Grantee: Ana Carolina Takakura Moreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity
• Grantee: Thiago dos Santos Moreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/12266-6 - Optogenetic stimulation of pre-Bötzinger complex neurons and the control of breathing in a mice model of Parkinson's disease
• Grantee: Luiz Marcelo Oliveira Santos
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate