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|Title:||THE ELECTROPHYSIOLOGICAL ACTIONS OF ADIPONECTIN IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS|
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|Authors/Affiliations:||1 Ted D. Hoyda*; 1 Alastair V. Ferguson; |
1 Queens University, Department of Physiology, Kingston, ON, Canada
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|Content:||Objectives: Adiponectin is an adipocyte derived hormone which acts in the brain to modulate energy homeostasis and autonomic function. The paraventricular nucleus of the hypothalamus (PVN), which plays a key role in controlling pituitary hormone secretion, has been suggested to be a central target for adiponectin actions. A number of hormones produced by PVN neurons have been implicated in the regulation of energy homeostasis including oxytocin, corticotropin releasing hormone and thyrotropin releasing hormone. Using RT-PCR and in situ hybridization techniques we have shown expression of both adiponectin receptors in the PVN. In this study we investigated the role of adiponectin in controlling the excitability of both magnocellular (MNC – oxytocin or vasopressin secreting) and parvocellular (neuroendocrine – CRH or TRH secreting or pre-autonomic) neurons within the PVN. |
Materials and Methods: Whole cell patch clamp recordings were made from hypothalamic slices including PVN from male Sprague Dawley rats. Following the completion of an experiment, cytoplasm was removed to perform an in situ single cell RT-PCR protocol to obtain the molecular phenotype of the neuron.
Results: Patch clamp recordings identified mixed (23% hyperpolarization (-5.8 ± 0.6mV), 43% depolarization (6.4 ± 0.9mV)) effects of adiponectin (10nM) in modulating the excitability of the majority of PVN neurons tested (n=135). These effects are maintained when cells are placed in synaptic isolation using tetrodotoxin. We hypothesized that these effects were cell type specific and assessed this by using single cell RT-PCR techniques to examine adiponectin actions on unique groups of cells within the PVN and to determine their expression profile of adiponectin receptors. Adiponectin was found to hyperpolarize 100% of MNC oxytocin neurons tested (n=6). MNC Vasopressin cells, while all affected (n=6) showed mixed responses. Further analysis indicates that oxytocin neurons express both receptors (6/7) while vasopressin neurons express either both receptors (3/8) or one receptor (5/8). In contrast 6/6 MNC neurons expressing both oxytocin and vasopressin were unaffected by adiponectin and expressed neither receptor (4/6). In addition neuroendocrine and pre-autonomic cells expressing either TRH or CRH almost all depolarize in the presence of adiponectin (TRH = 6/8, 5.4 ± 1.1mV, CRH = 4/5, 5.2 ± 2.2mV).
Conclusions: The results presented in this study suggest that adiponectin plays specific roles in controlling the excitability of unique groups of neurons in the PVN, actions which may underlie the mechanism by which adiponectin controls the metabolic state of the organism.
Research funding provided by grants from the Heart and Stoke Foundation (AVF) and CIHR Doctoral Research Award (TDH).
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