Changes in serotoninergic receptors 1A and 2A in the piglet brainstem after intermittent hypercapnic hypoxia (IHH) and nicotine.
We studied the effects of intermittent hypercapnic hypoxia (IHH) and/or nicotine on the immunoreactivity of serotoninergic (5-HT) receptors 1A and 2A in the piglet brainstem. These exposures were developed to mimic two common risk factors for Sudden Infant Death Syndrome (SIDS); prone sleeping (IHH) and cigarette smoke exposure (nicotine). Immunoreactivity for 5-HT(1A)R and 5-HT(2A)R were studied in four nuclei of the caudal medulla. Three exposure groups were compared to controls (n=14): IHH (n=10), nicotine (n=14), and nicotine+IHH (n=14). In control piglets, the immunoreactivity of 5-HT(1A)R was highest in the hypoglossal nucleus (XII), followed by inferior olivary nucleus (ION), nucleus of the solitary tract (NTS) and dorsal motor nucleus of the vagus (DMNV), whereas for 5-HT(2A)R, the immunoreactivity was highest in DMNV/NTS and then ION. Compared to controls, IHH reduced 5-HT(1A)R immunoreactivity in all studied nuclei (p<0.05) but had no effect on 5-HT(2A)R immunoreactivity. Nicotine reduced 5-HT(1A)R immunoreactivity in the DMNV, ION and NTS (p<0.001), and reduced 5-HT(2A)R immunoreactivity in DMNV/NTS (p<0.05). Nicotine+IHH reduced 5-HT(1A)R in DMNV, ION and NTS (p<0.001) but had no effect on 5-HT(2A)R immunoreactivity. Effects of nicotine on the DMNV were more significant in males compared to the females. These results show for the first time that IHH and/or nicotine can reduce 5-HT receptor immunoreactivity within functionally important nuclei of the piglet medulla. The findings support our hypothesis that 5-HT receptor abnormalities may be caused by postnatal exposures to clinically-relevant stimuli such as cigarette smoke exposure and/or prone sleeping.
Say
Meichien
M
Department of Paediatrics and Child Health, University of Sydney, NSW 2006, Australia.
Machaalani
Rita
R
Waters
Karen A
KA
D000818:Animals; D001933:Brain Stem / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D006935:Hypercapnia / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000096:biosynthesis*; D044402:Receptor, Serotonin, 5-HT2A / Q000096:biosynthesis*; D012737:Sex Factors; D013552:Swine; D013556:Swine, Miniature
D044402:Receptor, Serotonin, 5-HT2A; D044282:Receptor, Serotonin, 5-HT1A; D009538:Nicotine