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| Author(s): |
Deborah de Paula Romeu
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2024-10-08 |
| Examining board members: |
Vagner Roberto Antunes;
Pedro Lourenço Katayama;
Thiago dos Santos Moreira;
Simone Cristina Motta
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| Advisor: | Vagner Roberto Antunes |
| Abstract | |
Glucose is the most important energy substrate for maintaining body functions, particularly for the brain., and its plasma level is finely regulated through a complex interaction of hormonal and neuronal autonomic signals, from and to organs. Parasympathetic fibers innervating the liver originate from preganglionic neurons of the dorsal motor nucleus of the vagus (DMV), which receives monosynaptic glutamatergic neurotransmission from the C1 neurons in the ventrolateral medulla, being reasonable to suppose that this connection from C1 to DMV may comprise a neuronal circuitry as part of the glycemic control. We sought to assess whether there is apposition of the terminals of C1 neurons with the hepatic efferents, and which glycemic challenge may activate this circuitry. The experimental procedures were approved by the Ethics Committee of Animals Welfare of the ICB-USP (#9141070319). Male Wistar rats at eight weeks of age received an anterograde lentiviral vector PRSx8-ChR2-eYFP, delivered stereotaxically into the C1 region. After 30 days, the animals received injections of the retrograde tracer FluoroGold (FG) in the liver. After seven more days, these rats were deeply anesthetized and transcardially perfused to collect the brains. To assess which glycemic challenge could activate the C1-DMV pathway, we tested three stimuli: hypoglycemia (insulin; 1UI/kg, i.p), glucose overload (3.6g/kg; i.p.), and glucoprivation (2-deoxy-d-glucose; 400mg/kg), all by intraperitoneal injection. A control group received an intraperitoneal injection of 0,9% NaCl. After 90 minutos, rats were deeply anesthetized and transcardially perfused to fixate for immunoreaction to detect the FOS protein, as a marker for neuronal activation. We observed varicosities and fibers originating from the C1 neurons with apposition with the DMV FG+ neurons, suggesting that C1 neurons might excite theses parasympathetic preganglionic neurons. Glucose overload and glucoprivation led to an expressive FOS+ staining in the dorsal vagal complex, including the DMV, when compared to insulin-induced hypoglycemia and control groups. In two separated cases, we injected FG in the liver of the rats seven days prior the glycemic challenges. In this cases, some of these DMV-FOS+ neurons were also liver projecting, as confirmed by FG staining. Detection of FOS+ neurons also in the C1 region and the C1/A1 region overlap. The results lead us to suggest that the C1 neurons might recruit the parasympathetic efferent pathway to the liver, via the DMV neurons, as a reponse to glycemic challenges. (AU) | |
| FAPESP's process: | 22/02895-4 - Morphofunctional studies of the interaction between the catecholaminergic and cholinergic neurons in the medulla oblongata involved with the hepatic and pancreatic functions |
| Grantee: | Deborah de Paula Romeu |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |