Differential galanin expression by chemoreceptor neurons in mouse following long term hypercapnia challenge: Evidence for regulation of galanin transmission.
(2018) Society for Neuroscience (SfN) — Location: San Diego, USA
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- Abstract
- Glutamatergic chemoreceptor neurons in the retrotrapezoid nucleus (RTN) extensively project to the ventral respiratory column (VRC). VRC is located in the ventrolateral medulla (VLM) and generates the rhythmic breathing pattern. RTN chemoreceptors are critical in mediating the central respiratory chemoreflex, the primary homeostatic mechanism used by mammals to control blood carbon dioxide (CO2) levels. Interestingly, 50% of RTN neurons also express the inducible neuropeptide transmitter galanin. The functional role of these galaninergic RTN neurons remains unknown. Previous studies have demonstrated that injection of galanin into VRC induces apnoea by inhibiting breathing and ventilatory chemoreflex responses. We hypothesise that elevated environmental CO2 levels elicit chronic chemoreceptor stimulation, resulting in altered regulation of galanin expression in the RTN. Galanin signalling from the RTN then adjusts the central respiratory chemoreflex in the long term (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. The results showed that in the rostral brainstem, the distribution of galaninergic neurons was localised mainly to the RTN, inferior olive, paragiganticellular nucleus, nucleus of the solitary tract (NTS), and locus coeruleus (n=5). Also, the GalR1 positive neurons in the VLM were localised to nucleus ambiguous, VRC and A1 and C1 catecholaminergic populations (n=3). We next aimed to determine whether ppGal mRNA expression is altered in the RTN, VLM, NTS, or cerebellum, following hypercapnia challenge. Mice (n=5) were exposed either to room air (0% CO2) or hypercapnia (5% CO2, balance room air) for 3, 6 or 8 hours (short term challenge) or continuously for 10 days (long term challenge). Gene expression analysis was performed with quantitative PCR followed by one-way ANOVA. Our main findings were that ppGal mRNA levels increased by 62% in the RTN after long term hypercapnia (10 days) compared to room air (p<0.001). Whereas, 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. Overall, long term hypercapnia modulates galanin expression in the RTN suggesting a role for altered galaninergic transmission from RTN
- Affiliations
University of New South Wales
Citations
Dereli, A., & Kumar, N. N. (2018). Differential galanin expression by chemoreceptor neurons in mouse following long term hypercapnia challenge: Evidence for regulation of galanin transmission. Society for Neuroscience (SfN), San Diego, USA.