Electrophysiological Effects of Ghrelin in the Hypothalamic Paraventricular Nucleus Neurons
| Autor: | André S. Mecawi, Hanna M. Grover, Raoni C Dos-Santos, Alastair V. Ferguson, Luís Carlos Reis |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Vasopressin endocrine system vasopressin corticotropin-releasing hormone lcsh:RC321-571 03 medical and health sciences Corticotropin-releasing hormone Cellular and Molecular Neuroscience 0302 clinical medicine Internal medicine oxytocin medicine Patch clamp lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Original Research Chemistry digestive oral and skin physiology Glutamate receptor Electrophysiology 030104 developmental biology Endocrinology Oxytocin nervous system neuroendocrinology Magnocellular cell Ghrelin thyrotropin releasing hormone appetite regulation 030217 neurology & neurosurgery hormones hormone substitutes and hormone antagonists medicine.drug Neuroscience |
| Zdroj: | Frontiers in Cellular Neuroscience Frontiers in Cellular Neuroscience, Vol 12 (2018) |
| ISSN: | 1662-5102 |
| Popis: | The paraventricular nucleus (PVN) is involved in the control of sympathetic tone and the secretion of hormones, both functions known to be influenced by ghrelin, suggesting direct effect of ghrelin in this nucleus. However, the effects of ghrelin on the excitability of different PVN neuronal populations have not been demonstrated. This study assessed the effects of ghrelin on the activity of PVN neurons, correlating the responses to subpopulations of PVN neurons. We used a 64 multielectrode array to examine the effects of ghrelin administration on extracellular spike frequency in PVN neurons recorded in brain slices obtained from male Sprague-Dawley rats. Bath administration of 10 nM ghrelin increased (29/97, 30%) or decreased (37/97, 38%) spike frequency in PVN neurons. The GABAA and glutamate receptors antagonists abolish the decrease in spike frequency, without changes in the proportion of increases in spike frequency (23/53, 43%) induced by ghrelin. The results indicate a direct effect of ghrelin increasing PVN neurons activity and a synaptic dependent effect decreasing PVN neurons activity. The patch clamp recordings showed similar proportions of PVN neurons influenced by 10 nM ghrelin (33/95, 35% depolarized; 29/95, 30% hyperpolarized). Using electrophysiological fingerprints to identify specific subpopulations of PVN neurons we observed that the majority of pre-autonomic neurons (11/18 -61%) were depolarized by ghrelin, while both neuroendocrine (29% depolarizations, 40% hyperpolarizations), and magnocellular neurons (29% depolarizations, 21% hyperpolarizations) showed mixed responses. Finally, to correlate the electrophysiological response and the neurochemical phenotype of PVN neurons, cell cytoplasm was collected after recordings and RT-PCR performed to assess the presence of mRNA for vasopressin, oxytocin, thyrotropin (TRH) and corticotropin (CRH) releasing hormones. The single-cell RT-PCR showed that most TRH-expressing (4/5) and CRH-expressing (3/4) neurons are hyperpolarized in response to ghrelin. In conclusion, ghrelin either directly increases or indirectly decreases the activity of PVN neurons, this suggests that ghrelin acts on inhibitory PVN neurons that, in turn, decrease the activity of TRH-expressing and CRH-expressing neurons in the PVN. |
| Databáze: | OpenAIRE |
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