title: Exposure of Neonatal Mice to Tobacco Smoke Disturbs Synaptic Proteins and Spatial Learning and Memory from Late Infancy to Early Adulthood.
abstract: Exposure to environmental tobacco smoke (ETS) in the early postnatal period has been associated with several diseases; however, little is known about the brain effects of ETS exposure during this critical developmental period or the long-term consequences of this exposure. This study investigated the effects of the early postnatal ETS exposure on both reference and working memory, synaptic proteins and BDNF from late infancy to early adulthood (P3-P73). BALB/c mice were exposed to ETS generated from 3R4F reference research cigarettes (0.73 mg of nicotine/cigarette) from P3 to P14. Spatial reference and working memory were evaluated in the Morris water maze during infancy (P20-P29), adolescence (P37-P42) and adulthood (P67-P72). Synapsin, synaptophysin, PSD95 and brain-derived neurotrophic factor (BDNF) were assessed at P15, P35 and P65 by immunohistochemistry and immunoblotting. Mice that were exposed to ETS during the early postnatal period showed poorer performance in the spatial reference memory task. Specifically, the ETS-exposed mice exhibited a significantly reduced time and distance traveled in the target quadrant and in the platform location area than the controls at all ages evaluated. In the spatial working memory task, ETS disrupted the maintenance but not the acquisition of the critical spatial information in both infancy and adolescence. ETS also induced changes in synaptic components, including decreases in synapsin, synaptophysin, PSD95 and BDNF levels in the hippocampus. Exposure to ETS in the early postnatal period disrupts both spatial reference and working memory; these results may be related to changes in synaptogenesis in the hippocampus. Importantly, most of these effects were not reversed even after a long exposure-free period.
authors: Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo/SP, CEP: 05508-000, Brazil.
authors: Larissa Helena
authors: LH
authors: Torres
authors: Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo/SP, CEP: 05508-000, Brazil.
authors: Raphael C T
authors: RC
authors: Garcia
authors: Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo/SP, CEP: 05508-000, Brazil.
authors: Anne M M
authors: AM
authors: Blois
authors: Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo/SP, CEP: 05508-000, Brazil.
authors: Lívia M M
authors: LM
authors: Dati
authors: Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo/SP, CEP: 05508-000, Brazil.
authors: Ana Carolina
authors: AC
authors: Durão
authors: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo/SP, CEP: 05508-000, Brazil.
authors: Adilson Silva
authors: AS
authors: Alves
authors: Department of Clinical Pathology, School of Medicine, University of São Paulo, São Paulo/SP, CEP: 05403-010, Brazil.
authors: Maurílio
authors: M
authors: Pacheco-Neto
authors: Department of Pathology, School of Medicine, University of São Paulo, São Paulo/SP, CEP: 01246-903, Brazil.
authors: Thais
authors: T
authors: Mauad
authors: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo/SP, CEP: 05508-000, Brazil.
authors: Luiz R G
authors: LR
authors: Britto
authors: Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo/SP, CEP: 05508-900, Brazil.
authors: Gilberto Fernando
authors: GF
authors: Xavier
authors: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo/SP, CEP: 05508-900, Brazil.
authors: Rosana
authors: R
authors: Camarini
authors: Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo/SP, CEP: 05508-000, Brazil.
authors: Tania
authors: T
authors: Marcourakis
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000097:blood; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002248:Carbon Monoxide / Q000032:analysis; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning; D008565:Membrane Proteins / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D012907:Smoking / Q000009:adverse effects*; D065853:Spatial Learning; D065852:Spatial Memory; D013569:Synapses / Q000378:metabolism*; D013647:Task Performance and Analysis; D013997:Time Factors
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D008565:Membrane Proteins; D002248:Carbon Monoxide