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Orexin maintains wakefulness\/sleeping states, arousal, and rapid eye movement sleep, abnormalities of which have been reported in <jats:styled-content style=\"fixed-case\">SIDS<\/jats:styled-content>. This study examined the effects of two prominent risk factors for <jats:styled-content style=\"fixed-case\">SIDS<\/jats:styled-content>, intermittent hypercapnic hypoxia (<jats:styled-content style=\"fixed-case\">IHH<\/jats:styled-content>) (prone\u2010sleeping) and chronic nicotine exposure (cigarette\u2010smoking), on orexin A (OxA) and orexin B (OxB) expression in piglets. Piglets were randomly assigned to five groups: saline control (<jats:italic>n<\/jats:italic>\u00a0=\u00a07), air control (<jats:italic>n<\/jats:italic>\u00a0=\u00a07), nicotine [2\u00a0mg\/kg per day (14 days)] (<jats:italic>n<\/jats:italic>\u00a0=\u00a07), <jats:styled-content style=\"fixed-case\">IHH<\/jats:styled-content> (6\u00a0min of 7% O<jats:sub>2<\/jats:sub>\/8% <jats:styled-content style=\"fixed-case\">CO<\/jats:styled-content><jats:sub>2<\/jats:sub> alternating with 6\u2010min periods of breathing air, for four cycles) (<jats:italic>n<\/jats:italic>\u00a0=\u00a07), and the combination of nicotine and <jats:styled-content style=\"fixed-case\">IHH<\/jats:styled-content> (N\u00a0+\u00a0<jats:styled-content style=\"fixed-case\">IHH<\/jats:styled-content>) (<jats:italic>n<\/jats:italic>\u00a0=\u00a07). OxA\/OxB expression was quantified in the central tuberal hypothalamus [dorsal medial hypothalamus (<jats:styled-content style=\"fixed-case\">DMH<\/jats:styled-content>), perifornical area (PeF), and lateral hypothalamus], and the dorsal raphe, locus coeruleus of the pons. Nicotine and N\u00a0+\u00a0<jats:styled-content style=\"fixed-case\">IHH<\/jats:styled-content> exposures significantly increased: (i) orexin expression in the hypothalamus and pons; and (ii) the total number of neurons in the <jats:styled-content style=\"fixed-case\">DMH<\/jats:styled-content> and PeF. <jats:styled-content style=\"fixed-case\">IHH<\/jats:styled-content> decreased orexin expression in the hypothalamus and pons without changing neuronal numbers. Linear relationships existed between the percentage of orexin\u2010positive neurons and the area of pontine orexin immunoreactivity of control and exposure piglets. These results demonstrate that postnatal nicotine exposure increases the proportion of orexin\u2010positive neurons in the hypothalamus and fibre expression in the pons, and that <jats:styled-content style=\"fixed-case\">IHH<\/jats:styled-content> exposure does not prevent the nicotine\u2010induced increase. Thus, although both nicotine and <jats:styled-content style=\"fixed-case\">IHH<\/jats:styled-content> are risk factors for <jats:styled-content style=\"fixed-case\">SIDS<\/jats:styled-content>, it appears they have opposing effects on OxA and OxB expression, with the <jats:styled-content style=\"fixed-case\">IHH<\/jats:styled-content> exposure closely mimicking what we recently found in <jats:styled-content style=\"fixed-case\">SIDS<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/ejn.13246","type":"journal-article","created":{"date-parts":[[2016,4,2]],"date-time":"2016-04-02T20:37:39Z","timestamp":1459629459000},"page":"1612-1622","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Changes in orexinergic immunoreactivity of the piglet hypothalamus and pons after exposure to chronic postnatal nicotine and intermittent hypercapnic hypoxia"],"prefix":"10.1111","volume":"43","author":[{"given":"Nicholas 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