Characterization of the neural mechanisms involved in cardiovascular and respiratory changes in juvenile mice exposed to successive hypoxic challenges in the postnatal period

• Grant number: 24/10793-2
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2028
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Benedito Honorio Machado
• Grantee: Benedito Honorio Machado
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Daniela Accorsi Mendonça Eichenberger

Abstract

In the present project we will evaluate the impact of successive hypoxic challenges in the first 2 postnatal weeks of mice on the autonomic, cardiovascular and respiratory functions of these animals when they are 5-6 weeks old (juvenile). For this, female mice, immediately after giving birth, will be exposed together with their litters to the sustained hypoxia (SH) protocols for 5 days (P1-P5) and then to the chronic intermittent hypoxia (HCI) protocol for 10 days (P6 -P15) while in the control group after birth, the mothers and their litters will be kept in normoxia for 15 days (P1-P15). The pups will be kept with their mothers until weaning (21 days) and males and females will be studied 3-4 weeks after the end of the hypoxia or normoxia protocols, that is, when they will be 5-6 weeks old. Cardiovascular and respiratory parameters will be evaluated in awake animals and in the in situ working heart brainstem preparation, recordings from autonomic and respiratory nerves will be evaluated, as well as responses to the activation of peripheral chemoreceptors. Possible changes in synaptic transmission in the NTS neurons of these animals (hypoxia and normoxia groups) will also be investigated using the whole cell patch clamp technique, as well as possible changes in the neuron-astrocyte interaction in the NTS using multiphoton laser microscopy. With the results to be obtained through these different experimental approaches, we will be able to elucidate some of the neural mechanisms underlying the autonomic, cardiovascular and respiratory changes that occur in young people as a result of exposure to hypoxic challenges that occur in the postnatal phase. (AU)