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

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-Bötzinger Complex (preBötC) 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 µM) injected intraperitoneally or directly into the preBötC 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.

• Authors: Luiz M Oliveira, Liza Severs, Thiago S Moreira, Jan-Marino Ramirez, Ana C Takakura
• Journal: Brain research (Brain Res) Vol. 1815 Pg. 148448 (09 15 2023) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 37301422 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• 2H,3H,6aH-pyrrolidino(2'',1''-3',2')1,3-oxazino(6',5'-5,4)benzo(e)1, 4-dioxan-10-one
• Oxazines

Topics

• Animals
• Mice
• Disease Models, Animal
• Dopaminergic Neurons (metabolism, pathology)
• Oxazines (pharmacology, therapeutic use)
• Parkinson Disease (drug therapy, physiopathology)
• Respiratory Rate (drug effects)
• Substantia Nigra (pathology)
• Male
• Mice, Inbred C57BL