title: Low intensity, long term exposure to tobacco smoke inhibits hippocampal neurogenesis in adult mice.
abstract: Previous data have shown that high dose of nicotine administration or tobacco smoke exposure can reduce cell formation and the survival rate of adult-born neurons in the dentate gyrus. Here, we subjected adult mice to low intensity cigarette smoke exposure over long time periods. We did a 2×30min/day smoke exposure with two cigarettes per occasion over 1- or 2-months. Subsequently, we carried out a systematic quantitative histopathological analysis to assess the number of newborn neurons in the dentate gyrus. To investigate cell proliferation, the exogenous marker 5-bromo-2'-deoxyuridine (BrdU) was administered on the last experimental day and animals were sacrificed 2h later. To investigate the effect of tobacco smoke on the population of immature neurons, we quantified the number of doublecortin-positive (DCX+) neurons in the same animals. We found that exposing animals to cigarette smoke for 1- or 2-months had no influence on cell proliferation rate, but significantly reduced the number of DCX-positive immature neurons. Our tobacco smoke exposure regimen caused no substantial changes in respiratory functions, but histopathological analysis of the pulmonary tissue revealed a marked perivascular/peribronchial edema formation after 1-month and signs of chronic pulmonary inflammation after 2-months of cigarette smoke exposure. These data demonstrate that even mild exposure to cigarette smoke, without significantly affecting respiratory functions, can have a negative effect on adult-born neurons in the dentate gyrus, when applied over longer time periods. Our data indicate that besides nicotine other factors, such as inflammatory mediators, may also contribute to this effect.
authors.affiliation: MTA-PTE, Neurobiology of Stress Research Group, Szentágothai Research Center, University of Pécs, 7624 Pécs, Hungary.
authors.forename: Dávid
authors.initials: D
authors.lastname: Csabai
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, 7624 Pécs, Hungary.
authors.forename: Kata
authors.initials: K
authors.lastname: Csekő
authors.affiliation: MTA-PTE, Neurobiology of Stress Research Group, Szentágothai Research Center, University of Pécs, 7624 Pécs, Hungary.
authors.forename: Lilla
authors.initials: L
authors.lastname: Szaiff
authors.affiliation: MTA-PTE, Neurobiology of Stress Research Group, Szentágothai Research Center, University of Pécs, 7624 Pécs, Hungary.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Varga
authors.affiliation: Department of Laboratory Medicine, University of Pécs, Medical School, 7624 Pécs, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Miseta
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, 7624 Pécs, Hungary; MTA-PTE, Chronic Pain Research Group, Szentágothai Research Center, University of Pécs, 7624 Pécs, Hungary; PharmInVivo Ltd, 7629 Pécs, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
authors.affiliation: MTA-PTE, Neurobiology of Stress Research Group, Szentágothai Research Center, University of Pécs, 7624 Pécs, Hungary; Department of Laboratory Medicine, University of Pécs, Medical School, 7624 Pécs, Hungary. Electronic address: czeh.boldizsar@pte.hu.
authors.forename: Boldizsár
authors.initials: B
authors.lastname: Czéh
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D012129:Respiratory Function Tests; D012907:Smoking / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D014028:Tobacco Smoke Pollution; D001973:Bromodeoxyuridine
keywords: BrdU; Cigarette; Dentate gyrus; Doublecortin; Hippocampus; Inflammation; Nicotine; Smoking