Studies suggest that both hypertension and pregnancy are conditions associated with increased activity of the sympathetic nervous system. This increased activity is due, in part, to changes in the neurochemistry of the hypothalamic paraventricular nucleus (PVN). Work previously presented to the Physiological Society showed that the PVN of both spontaneously hypertensive (SHR) and late-term pregnant rats were associated with a significant decrease in the expression of the α1 and α5 subunits of the GABAA receptor. In the SHR, α5 expression was 97 ± 2% lower than Wistar controls. Furthermore, the SHR was also associated with a significant increase in expression of the GluN2A subunit of the NMDA receptor. These molecular changes could underpin the sympathoexcitation observed in these two states. We therefore aimed to assess whether these subunits were associated with presympathetic neurones (PSN) targeting the spinal cord. All experiments were performed in accordance with the Animals (Scientific Procedures) Act, 1986. Female Wistar rats (n=5) were anaesthetised with medetomindine (0.6mg/kg) and ketamine (30mg/kg) and secured into a stereotaxic frame. The T2 region of the spinal cord was exposed and 2µl of 2% Fluorogold (FG) was injected into the IML region. Animals were left to recover for 7 days before being perfused via the descending aorta with 4% paraformaldehyde. Brains were sectioned to 40µm and sections were stained for either the α1 or α5 subunit of the GABAA receptor or the GluN2A subunit of the NMDA receptor. This was visualised using a fluorescently-conjugating secondary antibody and viewed under epifluorescence. Quantitative analysis of the number of double labelled neurones show that 55.15 ± 2.5% of PSN express the α1 subunit and 73.29 ± 3.2% express the α5 subunit of the GABAA receptor. Furthermore, 54.95 ± 2.8% of PSNs express the GluN2A subunit of the NMDA receptor. Of those PSNs which did not express either the α1 or GluN2A subunits, many were found in close apposition to neurones which did express these subunits. Furthermore, a number of neurones were found to be positive for the either of the subunits in the absence of FG expression. These results suggest that a significant proportion of PSNs emanating from the PVN have the potential to be influenced by the changes in GABAA and NMDA receptor subunit expression presented previously. The changes observed are likely to significantly increase the level of neuronal activity of these neurones and thus sympathetic activity. Furthermore, it is likely that a number of other neuronal populations within the PVN are also likely to be influenced by these changes.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCC012
Poster Communications: Neurones in the PVN, which project to the intermediolateral cell column, express subunits of the GABAA and NMDA receptors known to be altered in hypertension and pregnancy
S. C. Cork1, P. L. Chazot1, S. Pyner1
1. School of Biological and Biomedical Sciences, University of Durham, Durham, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.