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Optogenetic stimulation of pre-Bötzinger complex neurons and the control of breathing in a mice model of Parkinson's disease

Grant number: 17/12266-6
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): September 01, 2017
Effective date (End): August 31, 2018
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Ana Carolina Thomaz Takakura
Grantee:Luiz Marcelo Oliveira Santos
Supervisor abroad: Jan-Marino Ramirez
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Seattle Children'S Research Institute, United States  
Associated to the scholarship:15/18842-3 - Orexinergic and aminergic mechanisms in respiratory control in an animal model of Parkinsons Disease, BP.DR


Parkinson´s disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra compacta (SNpc). We can observe non-motor symptoms as neuropsychiatric, sleep and breathing disorders. It was noticed in post-mortem humans brains and in 6-hydroxydopamine (6-OHDA) rat model of PD a significant reduction of neurokinin 1 receptor (NK1r) expression in the pre-Bötzinger complex (preBotC) (Benarroch et al. 2003; Tuppy et al., 2015). The preBötC is a functionally defined subregion of the VRC, that generates and transmits the rhythmic activity producing inspiration and is continually adjusted by particular mechanisms originated in the CNS to maintain blood gases homeostasis in the body (Ramirez and Richter 1996; Smith et al. 2009; Viemari et al. 2011; Zanella et al. 2014). Previous study has already demonstrated that in 6-OHDA rat model of PD there is a reduction of respiratory frequency at rest 40 days after PD induction. Based on that information our aim in the present project is investigate if there is any change in electrical activity of preBötC neurons in this PD´s model using mice and if selective activation of preBötC neurons by optogenetic is able to restore the ventilation in this PD´s model in mice. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
OLIVEIRA, LUIZ M.; HENRIQUE, ELISANDRA; BUSTELLI, ISABELLA B.; NETTO, NELSON F. C.; MOREIRA, THIAGO S.; TAKAKURA, ANA C.; CAETANO, ARIADINY L. Depletion of hypothalamic hypocretin/orexin neurons correlates with impaired memory in a Parkinson's disease animal model. Experimental Neurology, v. 323, JAN 2020. Web of Science Citations: 0.
OLIVEIRA, LUIZ M.; OLIVEIRA, MARIA A.; MORIYA, HENRIQUE T.; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Respiratory disturbances in a mouse model of Parkinson's disease. Experimental Physiology, v. 104, n. 5, p. 729-739, MAY 1 2019. Web of Science Citations: 3.
OLIVEIRA, LUIZ M.; FALQUETTO, BARBARA; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Orexinergic neurons are involved in the chemosensory control of breathing during the dark phase in a Parkinson's disease model. Experimental Neurology, v. 309, p. 107-118, NOV 2018. Web of Science Citations: 2.

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