Neuropeptides contribute to long term adaptation to respiratory stress
(2019) Australian Society for Medical Research (ASMR) — Location: Sydney, Australia
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- Abstract
- Introduction: Chemoreceptor neurons in the retrotrapezoid nucleus (RTN) are critical in mediating the central respiratory chemoreflex, the primary homeostatic mechanism controlling blood carbon dioxide (CO2) levels. Excitatory (glutamatergic) RTN neurons co-express specific subsets of neuropeptides (including Neuromedin B [NMB], galanin, PACAP, gastrin-releasing peptide [GRP]). We hypothesise that altered co-release of neuropeptides contributes to adaptation of the respiratory chemoreflex in response to long-term hypercapnia (such as occurs in respiratory disorders). Objective: Our first objective was to determine, if there are changes in neuropeptide mRNA expression within the RTN following short-term hypercapnia (SH: 6 or 8 hour exposure to 5 or 8% CO2) or long-term hypercapnia challenge (LH: 10 day exposure to 5 or 8% CO2), using qPCR. We also investigated alterations in the responsiveness of neuropeptide-containing RTN neurons after LH (8% CO2, 10 days) in vivo, by exposing mice to an acute chemoreflex challenge (AC: 1 hr of 10% CO2 exposure, 40% O2, 50% N2) after LH, followed by c-Fos (to identify activated neurons) and Phox2b (to identify RTN neurons) immunoreactivity combined with in situ hybridisation for neuropeptides. Methods and Results: BL6/J mice (n=5-7/group) were used. We found that SH downregulates ppGal whereas LH upregulates ppGal in the rostral RTN. In the caudal RTN, in contrast, ppGal, ppGRP and ppNMB were all downregulated following SH and upregulated following LH. As previously described, ~30% of RTN neurons were activated following AC, compared to baseline conditions (no AC) (p<0.05). In mice that had LH, whilst 26% of RTN neurons were activated following AC, which was not statistically significant to RTN neurons that were activated under baseline conditions (LH, no AC). Conclusions: LH upregulates the expression of at least 3 inducible neuropeptides within the RTN. RTN chemoreceptor activity is altered following LH, suggesting adaptation of the respiratory chemoreflex circuit.
- Affiliations
University of New South Wales
Citations
Kumar, N. N., Dereli, A., & Yaseen, Z. (2019). Neuropeptides contribute to long term adaptation to respiratory stress. Australian Society for Medical Research (ASMR), Sydney, Australia.