A role for neuropeptide transmission in central respiratory chemoreception following hypercapnia.
(2018) “Kioloa at Newcastle” Neuroscience Colloquium — Location: Newcastle, Australia
Files
No attached file found for this publication.
Details
- Authors
- Abstract
- ntroduction: Glutamatergic chemoreceptor neurons in the retrotrapezoid nucleus (RTN) are critical in mediating the central respiratory chemoreflex, the primary homeostatic mechanism used by mammals to control blood carbon dioxide (CO2) levels. RTN neurons extensively project to the ventral respiratory column (VRC), which is located in the ventrolateral medulla (VLM) and generates the rhythmic breathing pattern. Interestingly, 50% of RTN neurons also express the inducible neuropeptide transmitter galanin (Stornetta et al., 2009, Spirovski et al., 2012) however the function of galanin in these neurons remains unknown. Previous studies have demonstrated that injection of galanin into the VRC induces apnoea by inhibiting breathing and ventilatory chemoreflex responses (Abbott SB et al., 2009). We hypothesise that long-term exposure to elevated environmental CO2 elicits chronic chemoreceptor stimulation, resulting in altered regulation of galanin expression in the RTN. Furthermore, galanin signalling from the RTN adjusts the central respiratory chemoreflex in the long-term (neuronal plasticity). Aims: We aimed first to determine the distribution of preprogalanin (ppGal) and galanin receptor 1 (GalR1) mRNA in the mouse RTN and VLM respectively, using in situ hybridisation (ISH). We also aimed to determine whether preprogalanin (ppGal) mRNA expression is altered in the RTN, VLM, nucleus of the solitary tract (NTS) or cerebellum following short-term and long-term hypercapnia challenge, using qPCR. Method: For the short-term hypercapnia challenge, adult C57Bl6 mice were either exposed to normoxia (room air control, 0% CO2) or hypercapnia (5% CO2, balance room air) for 3, 6 or 8 hours. For chronic hypercapnia challenge, mice were exposed to either normoxia (room air control, 0% CO2) or hypercapnia (5% CO2, balance room air) for 10 days. Following the challenge, animals were euthanized and tissues (RTN, VRC, NTS and cerebellum) were isolated for galanin gene expression analysis with quantitative PCR (qPCR) followed by one-way ANOVA. Results; ISH revealed that in the rostral brainstem, the distribution of galaninergic (ppGal+) neurons is restricted to the mouse RTN, inferior olive, paragiganticellular nucleus NTS and LC; none of ppGal+ neurons are tyrosine hydroxylase positive (TH+). Also, the distribution of GalR1 positive neurons was shown in the VLM including nucleus ambiguous, ventral respiratory column and A1 and C1 catecholaminergic populations with a very small number double labelled with TH. qPCR results showed that ppGal mRNA levels increased by 62% in the RTN after long-term hypercapnia (10 days) compared to room air (p<0.001). No changes in gene expression were observed in the RTN following short-term challenge. Conversely, ppGal expression in the VLM decreased by 32% following 6 hour short-term hypercapnia (p<0.05) however no changes were observed after long-term challenge. ppGal expression was not altered in the NTS and cerebellum for any of the challenges. Conclusion: Overall, long-term hypercapnia modulates galanin expression in the RTN suggesting a role for altered galaninergic transmission from RTN neurons during adaptation to long-term respiratory challenges.
- Affiliations
University of New South Wales
Citations
Dereli, A., McMullan, S., & Kumar, N. N. (2018). A role for neuropeptide transmission in central respiratory chemoreception following hypercapnia. “Kioloa at Newcastle” Neuroscience Colloquium, Newcastle, Australia.