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Morphofunctional studies of the interaction between the catecholaminergic and cholinergic neurons in the medulla oblongata involved with the hepatic and pancreatic functions

Grant number: 22/02895-4
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): October 01, 2022
Effective date (End): December 31, 2023
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Vagner Roberto Antunes
Grantee:Deborah de Paula Romeu
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Glucose is the main energetic source to the organism, including the brain, and it can be obtained by the food and by metabolic process involving the liver and pancreas. Changes on glycemia can be extremely dangerous to the body, and to avoid them there are several physiological mechanisms to keep the glucose levels at a regular range, which involves pancreatic hormones insulin and glucagon, both acting on the liver as the main target to control the glycemia. Not only this systemic and local mechanisms are involved in the control of glycemia, but also the autonomic nervous system with sympathetic and parasympathetic efferent branches to the liver and pancreas. The main sympathetic efferents innervating the liver and the pancreas comprises neuronal projections to the intermediolateral cell column in the spinal cord and adrenal gland, and the parasympathetic component has the involvement of neurons from the Dorsal Motor nucleus of the Vagus (DMV). Among several neural connections converging to the DMV, one of particular interest in this study is the projections from the C1, a subset of catecholaminergic neurons in the ventrolateral medulla. Comprising the main cluster of adrenergic neurons in the medulla, C1 neurons are involved in a circuitry recruited during acute stresses to the organism, such as hypotension, hypoxia and hypoglycemia. Recently, neuroanatomical studies have shown a monosynaptic glutamatergic neurotransmission between the C1 neurons and the parasympathetic preganglionic neurons of the DMV. Considering glucose as an essential energetic source, particularly to the brain, it is reasonable to suppose that the projection from C1 to DMV may comprise a significant neuronal circuitry as part of the glycemic control, through the parasympathetic efferents to the liver and pancreas. Our preliminary data have shown a close apposition of DMV-liver projecting neurons with terminals and varicosities from C1, suggesting that C1 may excite these cholinergic neurons and affects the glycemia. Nevertheless, we should not rule out the hypothesis that parasympathetic preganglionic cells at the DMV level also can innervate other organs, such as the pancreas. Keeping those evidence in mind, here we aim to use a combination of neuroanatomical and optogenetic techniques to investigate the interactions between C1 and DMV, using anterograde and retrograde neural tracers and immunohistochemical techniques for multiple labeling. Neuroanatomic data will be analyzed three-dimensionally and by electron microscopy for a greater refinement. Functional optogenetic experiments will also allow us to analyze the function of C1-DMV projections and its implication on glucose homeostasis of conscious rats. (AU)

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