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1.
J Neuroendocrinol ; 32(6): e12855, 2020 06.
Article in English | MEDLINE | ID: mdl-32436241

ABSTRACT

Phoenixin (PNX) is a neuropeptide shown to play roles in the control of reproduction. The nucleus of the solitary tract (NTS), a critical autonomic integrating centre in the hindbrain, is one of many areas with dense expression of PNX. Using coronal NTS slices obtained from male Sprague-Dawley rats, the present study characterised the effects of PNX on both spike frequency and membrane potential of NTS neurones. Extracellular recordings demonstrated that bath-applied 10 nmol L-1 PNX increased the firing frequency in 32% of NTS neurones, effects which were confirmed with patch-clamp recordings showing that 50% of NTS neurones tested depolarised in response to application of the peptide. Surprisingly, the responsiveness to PNX in NTS neurones then declined suddenly to 9% (P < 0.001). This effect was subsequently attributed to stress associated with construction in our animal care facility because PNX responsiveness was again observed in slices from rats delivered and maintained in a construction-free facility. We then examined whether this loss of PNX responsiveness could be replicated in rats placed on a chronic stress regimen involving ongoing corticosterone (CORT) treatment in the construction-free facility. Slices from animals treated in this way showed a similar lack of neuronal responsiveness to PNX (9.1 ± 3.9%) within 2 weeks of CORT treatment. These effects were specific to PNX responsiveness because CORT treatment had no effect on the responsiveness of NTS neurones to angiotensin II. These results are the first to implicate PNX with respect to directly controlling the excitability of NTS neurones and also provide intriguing data showing the plasticity of these effects associated with environmental and glucocorticoid stress levels of the animal.


Subject(s)
Cellular Microenvironment , Glucocorticoids/adverse effects , Neurons/drug effects , Peptide Hormones/pharmacology , Solitary Nucleus/drug effects , Action Potentials/drug effects , Animals , Cellular Microenvironment/drug effects , Cellular Microenvironment/physiology , Electric Stimulation , Electrophysiological Phenomena/drug effects , Male , Membrane Potentials/drug effects , Neurons/physiology , Rats , Rats, Sprague-Dawley , Solitary Nucleus/cytology , Solitary Nucleus/physiology , Stress, Physiological/drug effects , Stress, Physiological/physiology
2.
Front Cell Neurosci ; 12: 275, 2018.
Article in English | MEDLINE | ID: mdl-30210300

ABSTRACT

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.

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