title: Effect of hyperoxic exposure during early development on neurotrophin expression in the carotid body and nucleus tractus solitarii.
abstract: Synaptic activity can modify expression of neurotrophins, which influence the development of neuronal circuits. In the newborn rat, early hyperoxia silences the synaptic activity and input from the carotid body, impairing the development and function of chemoreceptors. The purpose of this study was to determine whether early hyperoxic exposure, sufficient to induce hypoplasia of the carotid body and decrease the number of chemoafferents, would also modify neurotrophin expression within the nucleus tractus solitarii (nTS). Rat pups were exposed to hyperoxia (fraction of inspired oxygen 0.60) or normoxia until 7 or 14 days of postnatal development (PND). In the carotid body, hyperoxia decreased brain-derived neurotrophic factor (BDNF) protein expression by 93% (P = 0.04) after a 7-day exposure, followed by a decrease in retrogradely labeled chemoafferents by 55% (P = 0.004) within the petrosal ganglion at 14 days. Return to normoxia for 1 wk after a 14-day hyperoxic exposure did not reverse this effect. In the nTS, hyperoxia for 7 days: 1) decreased BDNF gene expression by 67% and protein expression by 18%; 2) attenuated upregulation of BDNF mRNA levels in response to acute hypoxia; and 3) upregulated p75 neurotrophic receptor, truncated tropomyosin kinase B (inactive receptor), and cleaved caspase-3. These effects were not observed in the locus coeruleus (LC). Hyperoxia for 14 days also decreased tyrosine hydroxylase levels by 18% (P = 0.04) in nTS but not in the LC. In conclusion, hyperoxic exposure during early PND reduces neurotrophin levels in the carotid body and the nTS and shifts the balance of neurotrophic support from prosurvival to proapoptotic in the nTS, the primary brain stem site for central integration of sensory and autonomic inputs.
authors.affiliation: Department of Pediatrics, Division of Neonatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-3200, USA.
authors.forename: Raul
authors.initials: R
authors.lastname: Chavez-Valdez
authors.forename: Ariel
authors.initials: A
authors.lastname: Mason
authors.forename: Ana R
authors.initials: AR
authors.lastname: Nunes
authors.forename: Frances J
authors.initials: FJ
authors.lastname: Northington
authors.forename: Clarke
authors.initials: C
authors.lastname: Tankersley
authors.forename: Rajni
authors.initials: R
authors.lastname: Ahlawat
authors.forename: Sheree M
authors.initials: SM
authors.lastname: Johnson
authors.forename: Estelle B
authors.initials: EB
authors.lastname: Gauda
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002344:Carotid Body / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D004195:Disease Models, Animal; D018496:Hyperoxia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D017552:Solitary Nucleus / Q000254:growth & development / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C068313:Ngfr protein, rat; D014446:Tyrosine 3-Monooxygenase; D011494:Protein Kinases; C041311:tropomyosin kinase; C505410:Casp3 protein, rat; D053148:Caspase 3