A potential role for galanin in the chemosensory response to chronic intermittent hypoxia
(2017) Interuniversity Neuroscience and Mental Health Conference — Location: Sydney, Australia
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- Abstract
- Chemoreceptor neurons in the retrotrapezoid nucleus (RTN) play a crucial role in the respiratory chemoreflex response to hypercapnia and hypoxia. A subpopulation of RTN neurons express the inhibitory neuropeptide galanin. Microinjection of galanin into the ventral respiratory column (VRC), the brain region that generates the rhythmic breathing pattern, inhibits breathing in the rat. Monosynaptic projections from galaninergic RTN chemosensory neurons to the VRC have been demonstrated in the rat. The mechanism by which galanin inhibits ventilation and the receptor substrates involved needs to be elucidated to understand its role in the CNS control of breathing. We aimed to examine the distribution of galanin receptor subtype 1 (GalR1) mRNA in the mouse brain and map brainstem populations that project to the VRC. We also aimed to quantify preprogalanin (ppGal) mRNA levels in RTN and ventrolateral medulla (VLM) after exposure to chronic intermittent hypoxia (CIH). Brainstem tissue sections from adult male C57BL/6 mice (n=4) were processed for either GalR1 or ppGal in situ hybridisation. Neonatal Sprague Dawley rats (n=4-5) were exposed to CIH (12%O2, 1 hour/day for 5 days). The results show that there is moderate expression of GalR1 in nucleus of the solitary tract (NTS), RTN, VRC, locus coeruleus (LC), median raphe, thalamus, hypothalamus, amygdala and lateral septum. ppGal mRNA is expressed in NTS, RTN, inferior olive, spinal trigeminal nucleus (SP5), LC and hypothalamus. Following injection of the retrograde tracer, CTB-555, into the VRC in adult mice, we identified specific neuronal populations that project to VRC including NTS, as described previously (Alheid G et al, 2011), and dorsal raphe, LC, parabrachial nucleus, Kolliker fuse nucleus, cuneate nucleus, SP5 and inferior olive. The CIH results showed that there was a significant decrease of ppGal expression in the VLM and RTN in mice exposed to intermittent 12% O2 compared to normoxia (p<0.01). In conclusion, we have identified all brainstem projections to the VRC in the mouse. The expression of galanin in RTN and GalR1 in VRC in the mouse provides for a circuit for homeostatic regulation of respiration by galanin. This is supported by decreased ppGal expression in both RTN and VLM during CIH.
- Affiliations
University of New South Wales
Citations
Dereli, A., Jones, N., McMullan, S., & Kumar, N. N. (2017). A potential role for galanin in the chemosensory response to chronic intermittent hypoxia. Interuniversity Neuroscience and Mental Health Conference, Sydney, Australia.