Differential neuropeptide expression by central chemoreceptor neurons following long-term versus short-term hypercapnia: a role for neuropeptides in respiratory neural plasticity.

Dereli, Ayse;Kumar, Natasha N
(2018) Central Cardio-Respiratory Control: Future Directions Conference (CCRCFD), — Location: Melbourne, Australia

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Abstract
Glutamatergic chemoreceptor neurons in the retrotrapezoid nucleus (RTN) are critical in mediating the central respiratory chemoreflex. 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 RTN neurons also express inducible neuropeptide transmitters including the inhibitory galanin (50%), the excitatory gastrin-releasing peptide (GRP) and neuromedin B (NMB, 75%). The function of these neuropeptides in the RTN remains unclear. Here, we hypothesise that long-term exposure to elevated environmental CO2 elicits an increase in inhibitory and a decrease in excitatory neuropeptide expression in the RTN which adjusts central respiratory chemoreflex signalling leading to neuronal plasticity. We aimed first to determine the distribution of preprogalanin (ppGal) and galanin receptor 1 (GalR1) mRNA in the adult C57Bl6 mouse RTN and VLM respectively, using qualitative PCR and in situ hybridisation. We next aimed to determine whether ppGal, preproneuromedin B (ppNMB) and preprogastrin-releasing peptide (ppGRP) mRNA expression was altered in the RTN, VLM, or cerebellum, following hypercapnia challenge. Mice were exposed either to room air or hypercapnia (5 or 8%CO2, balance room air) for 6 or 8 hours (short-term challenge) or continuously for 10 days (long-term challenge). Gene expression analysis was performed with quantitative PCR. Distribution studies showed that in the rostral brainstem, galaninergic neurons were localised mainly to the RTN, inferior olive, paragiganticellular nucleus, nucleus of the solitary tract and locus coeruleus (n=5). Also, the GalR1 positive neurons in the VLM were localised to nucleus ambiguus, VRC and A1/C1 catecholaminergic populations (n=3). Gene expression studies (n=5 each) showed that in the RTN, ppGal mRNA levels decreased by 30% (p<0.01) following short-term hypercapnia (5%CO2) and increased by either 70% (5%CO2, p<0.001) or 30% (8%CO2, p<0.05) after long-term hypercapnia, while ppNMB or ppGRP expression remained unaffected. In the VLM, while short-term hypercapnia (5%CO2) decreased ppGal, ppNMB and ppGRP expression by 30% (p<0.05), 40% (p<0.01) and 50% (p<0.01) respectively, long-term hypercapnia (8%CO2) increased ppGal expression by 50% (p<0.01) and ppNMB expression by 30% (p<0.05). None of the challenges altered the expression of the neuropeptides in the cerebellum. Overall, long-term hypercapnia modulates ppGal expression in the RTN, ppGal and ppNMB expression in the VLM suggesting a role for altered peptidergic transmission during adaptation to long-term respiratory challenges.
Affiliations
  • University of New South Wales

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Dereli, A., & Kumar, N. N. (2018). Differential neuropeptide expression by central chemoreceptor neurons following long-term versus short-term hypercapnia: a role for neuropeptides in respiratory neural plasticity. Central Cardio-Respiratory Control: Future Directions Conference (CCRCFD), Melbourne, Australia.