Perinatal Nicotine Reduces Chemosensitivity of Medullary 5-HT Neurons after Maturation in Culture.
Neuroscience
; 446: 80-93, 2020 10 15.
Article
em En
| MEDLINE
| ID: mdl-32818601
ABSTRACT
Perinatal exposure to nicotine produces ventilatory and chemoreflex deficits in neonatal mammals. Medullary 5-HT neurons are putative central chemoreceptors that innervate respiratory nuclei and promote ventilation, receive cholinergic input and express nicotinic acetylcholine receptors (nAChRs). Perforated patch clamp recordings were made from cultured 5-HT neurons dissociated from the medullary raphé of 0-3â¯day old mice expressing enhanced yellow fluorescent protein driven by the enhancer region for PET1 (ePet-EYFP). The effect of exposure to low (6â¯mgâ¯kg-1day-1) or high (60â¯mgâ¯kg-1day-1) doses of nicotine in utero (prenatal), in culture (postnatal), or both and the effect of acute nicotine exposure (10⯵M), were examined on baseline firing rate (FR at 5% CO2, pHâ¯=â¯7.4) and the change in FR with acidosis (9% CO2, pH 7.2) in young (12-21â¯days in vitro, DIV) and older (≥22 DIV) acidosis stimulated 5-HT neurons. Nicotine exposed neurons exhibited â¼67% of the response to acidosis recorded in neurons given vehicle (pâ¯=â¯0.005), with older neurons exposed to high dose prenatal and postnatal nicotine, exhibiting only 28% of that recorded in the vehicle neurons (pâ¯<â¯0.01). In neurons exposed to low or high dose prenatal and postnatal nicotine, acute nicotine exposure led to a smaller increase in FR (â¼+51% vs +168%, pâ¯=â¯0.026) and response to acidosis (+6% vs +67%, pâ¯=â¯0.014) compared to vehicle. These data show that exposure to nicotine during development reduces chemosensitivity of 5-HT neurons as they mature, an effect that may be related to the abnormal chemoreflexes reported in rodents exposed to nicotine in utero, and may cause a greater risk for sudden infant death syndrome (SIDS).
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MEDLINE
Assunto principal:
Serotonina
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Nicotina
Idioma:
En
Ano de publicação:
2020
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Article