Impaired chemosensory control of breathing after depletion of bulbospinal catecholaminergic neurons in rats

Author(s)

Malheiros-Lima, Milene R. ^[1] ; Totola, Leonardo T. ^[1] ; Takakura, Ana C. ^[2] ; Moreira, Thiago S. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Av Prof Lineu Prestes, 1524, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY; v. 470, n. 2, p. 277-293, FEB 2018.
• Web of Science Citations: 2

Abstract

Bulbospinal catecholaminergic neurons located in the rostral aspect of the ventrolateral medulla (C1 neurons) or within the ventrolateral pons (A5 neurons) are involved in the regulation of blood pressure and sympathetic outflow. A stimulus that commonly activates the C1 or A5 neurons is hypoxia, which is also involved in breathing activation. Although pharmacological and optogenetic evidence suggests that catecholaminergic neurons also regulate breathing, a specific contribution of the bulbospinal neurons to respiratory control has not been demonstrated. Therefore, in the present study, we evaluated whether the loss of bulbospinal catecholaminergic C1 and A5 cells affects cardiorespiratory control during resting, hypoxic (8% O-2), and hypercapnic (7% CO2) conditions in unanesthetized rats. Thoracic spinal cord (T4-T8) injections of the immunotoxin anti-dopamine beta-hydroxylase-saporin (anti-D beta H-SAP-2.4 ng/100 nl) and the retrograde tracer Fluor-Gold or ventrolateral pontine injections of 6-OHDA were performed in adult male Wistar rats (250-280 g, N = 7-9/group). Anti-D beta H-SAP or 6-OHDA eliminated most bulbospinal C1 and A5 neurons or A5 neurons, respectively. Serotonergic neurons and astrocytes were spared. Depletion of the bulbospinal catecholaminergic cells did not change cardiorespiratory variables under resting condition, but it did affect the response to hypoxia and hypercapnia. Specifically, the increase in the ventilation, the number of sighs, and the tachycardia were reduced, but the MAP increased during hypoxia in anti-D beta H-SAP-treated rats. Our data reveal that the bulbospinal catecholaminergic neurons (A5 and C1) facilitate the ventilatory reflex to hypoxia and hypercapnia. (AU)

• FAPESP's process: 14/07698-6 - Contribution of catecholaminergic neurons of the rostral ventrolateral medulla in the respiratory control
• Grantee: Milene Rodrigues Malheiros Lima
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/22406-1 - Respiratory anatomofunctional changes observed in an experimental model of Parkinson Disease
• Grantee: Ana Carolina Takakura Moreira
• Support Opportunities: Regular Research Grants