Author: Junichi Sakaguchi
Sakaguchi, Junichi, 2024 Functional Link between the Amygdala and Brown Adipose Tissue Thermogenesis, Flinders University, College of Medicine and Public Health
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Introduction:
The amygdala plays a crucial role in emotion. When animals are in emotionally significant situations, their body temperature rises. This increase in body temperature is known to be due to heat production in brown adipose tissue (BAT), which is controlled by the sympathetic nervous system. The amygdala may trigger a sympathetic drive to BAT, contributing to the rise in body temperature. This project aims to identify the role of the amygdala in BAT thermogenesis in rats, specifically whether activation of neurons in the amygdala can cause BAT thermogenesis in anesthetized rats. Known brain circuits controlling BAT thermogenesis include the dorsomedial hypothalamus (DMH) and the medullary raphe. Therefore, this project also investigates whether the medullary raphe mediates amygdala-induced BAT thermogenesis.
Method:
In this project, we measured the electrical signals from the sympathetic nerves controlling the BAT in anesthetized rats (Spargue-Dawley, male). Since BAT is regulated by the sympathetic nervous system, using anesthetized rats allowed us to record these signals. A pharmacological approach was used to control the activity of neurons in the amygdala and the raphe nuclei. Neurons were activated by disinhibition using bicuculline, a GABA receptor antagonist. This activation aimed to determine whether drug-induced BAT thermogenesis could be elicited by stimulating neurons in the amygdala. Subsequently, muscimol, a GABA receptor agonist, was administered to the raphe nuclei to inhibit amygdala-induced BAT thermogenesis. During the experiments, several physiological parameters were recorded, including BAT sympathetic nerve activity, end-tidal CO2, BAT temperature, body temperature, skin temperature, heart rate, and arterial blood pressure. After recording, perfusion and brain extraction were performed for sectioning and immunostaining. Injection sites were observed under a microscope using Horse Radish Peroxidase (HRP) and fluorescent beads to identify the locations of the injections and determine if they corresponded to the observed responses.
Result:
It was found that activating neurons in the amygdala with bicuculline caused an increase in BAT sympathetic nerve activity and BAT temperature. When bicuculline was injected outside the amygdala, the BAT thermogenic response was minimal. Administration of muscimol to the raphe pallidus inhibited amygdala-induced BAT thermogenesis, while drug administration outside this brain region did not produce an inhibitory response.
Conclusion:
These results indicate that the amygdala provides excitatory drives to BAT via the medullary raphe. Future research aims to understand the newly discovered autonomic functions of the amygdala and how its emotional functions trigger BAT thermogenesis in conscious animal experiments. Bicuculline-induced BAT thermogenesis suggests that tonic GABAergic inputs into the amygdala plays an important role in this response. It is also important to elucidate GABAergic system in the amygdala involved in BAT thermogenesis. This project has highlighted new functions of the amygdala and suggested that autonomic functions could serve as valuable biomarkers in amygdala research.
Keywords: Brown Adipose Tissue, the amygdala, the medullary raphe, thermogenesis, sympathetic nervous system, GABAergic neurons, bicuculline, muscimol
Subject: Biotechnology thesis
Thesis type: Masters
Completed: 2024
School: College of Medicine and Public Health
Supervisor: Yoichiro Otsuka