title: Antenatal insults modify newborn olfactory function by nitric oxide produced from neuronal nitric oxide synthase.
abstract: Newborn feeding, maternal, bonding, growth and wellbeing depend upon intact odor recognition in the early postnatal period. Antenatal stress may affect postnatal odor recognition. We investigated the exact role of a neurotransmitter, nitric oxide (NO), in newborn olfactory function. We hypothesized that olfactory neuron activity depended on NO generated by neuronal NO synthase (NOS). Utilizing in vivo functional manganese enhanced MRI (MEMRI) in a rabbit model of cerebral palsy we had shown previously that in utero hypoxia-ischemia (H-I) at E22 (70% gestation) resulted in impaired postnatal response to odorants and poor feeding. With the same antenatal insult, we manipulated NO levels in the olfactory neuron in postnatal day 1 (P1) kits by administration of intranasal NO donors or a highly selective nNOS inhibitor. Olfactory function was quantitatively measured by the response to amyl acetate stimulation by MEMRI. The relevance of nNOS to normal olfactory development was confirmed by the increase of nNOS gene expression from fetal ages to P1 in olfactory epithelium and bulbs. In control kits, nNOS inhibition decreased NO production in the olfactory system and increased MEMRI slope enhancement. In H-I kits the MEMRI slope did not increase, implicating modification of endogenous NO-mediated olfactory function by the antenatal insult. NO donors as a source of exogenous NO did not significantly change function in either group. In conclusion, olfactory epithelium nNOS in newborn rabbits probably modulates olfactory signal transduction. Antenatal H-I injury remote from delivery may affect early functional development of the olfactory system by decreasing NO-dependent signal transduction.
authors: Department of Pediatrics, NorthShore University HealthSystem Research Institute, Evanston, IL, USA. oldrobys@gmail.com
authors: Alexander
authors: A
authors: Drobyshevsky
authors: Lei
authors: L
authors: Yu
authors: Yirong
authors: Y
authors: Yang
authors: Syed
authors: S
authors: Khalid
authors: Kehuan
authors: K
authors: Luo
authors: Rugang
authors: R
authors: Jiang
authors: Haitao
authors: H
authors: Ji
authors: Matthew
authors: M
authors: Derrick
authors: Leslie
authors: L
authors: Kay
authors: Richard B
authors: RB
authors: Silverman
authors: Sidhartha
authors: S
authors: Tan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002547:Cerebral Palsy / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D009830:Olfactory Bulb / Q000201:enzymology / Q000254:growth & development; D009831:Olfactory Mucosa / Q000201:enzymology / Q000254:growth & development; D055696:Olfactory Perception / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I