title: Long-term effects of gestational nicotine exposure and food-restriction on gene expression in the striatum of adolescent rats.
abstract: Gestational exposure to environmental toxins such as nicotine may result in detectable gene expression changes in later life. To investigate the direct toxic effects of prenatal nicotine exposure on later brain development, we have used transcriptomic analysis of striatal samples to identify gene expression differences between adolescent Lister Hooded rats exposed to nicotine in utero and controls. Using an additional group of animals matched for the reduced food intake experienced in the nicotine group, we were also able to assess the impact of imposed food-restriction on gene expression profiles. We found little evidence for a role of gestational nicotine exposure on altered gene expression in the striatum of adolescent offspring at a significance level of p<0.01 and |log2 fold change >0.5|, although we cannot exclude the possibility of nicotine-induced changes in other brain regions, or at other time points. We did, however, find marked gene expression differences in response to imposed food-restriction. Food-restriction resulted in significant group differences for a number of immediate early genes (IEGs) including Fos, Fosb, Fosl2, Arc, Junb, Nr4a1 and Nr4a3. These genes are associated with stress response pathways and therefore may reflect long-term effects of nutritional deprivation on the development of the stress system.
authors.affiliation: Medical Research Council (MRC), Social, Genetic and Developmental Psychiatry (SGDP) centre, Institute of Psychiatry, King's College London, London, United Kingdom ; Computational Genomics Analysis and Training (CGAT), Medical Research Council (MRC) Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Ilott
authors.affiliation: Department of addictions, Institute of Psychiatry, King's College London, London, United Kingdom, ; Experimental Psychology, University of Oxford, Oxford, United Kingdom.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Schneider
authors.affiliation: Medical Research Council (MRC), Social, Genetic and Developmental Psychiatry (SGDP) centre, Institute of Psychiatry, King's College London, London, United Kingdom ; University of Exeter Medical School, Exeter, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mill
authors.affiliation: Medical Research Council (MRC), Social, Genetic and Developmental Psychiatry (SGDP) centre, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Leonard
authors.initials: L
authors.lastname: Schalkwyk
authors.affiliation: Departamento de Psicologia do Desenvolvimento e da Personalidade, Instituto de Psicologia, Universidade Federal do Rio Grande do Sul, Porto Alegre-RS, Brazil.
authors.forename: Giovana
authors.initials: G
authors.lastname: Brolese
authors.affiliation: Departamento de Psicologia do Desenvolvimento e da Personalidade, Instituto de Psicologia, Universidade Federal do Rio Grande do Sul, Porto Alegre-RS, Brazil.
authors.forename: Lisiane
authors.initials: L
authors.lastname: Bizarro
authors.affiliation: Department of addictions, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Stolerman
authors.affiliation: Medical Research Council (MRC), Social, Genetic and Developmental Psychiatry (SGDP) centre, Institute of Psychiatry, King's College London, London, United Kingdom ; University of Exeter Medical School, Exeter, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Dempster
authors.affiliation: Medical Research Council (MRC), Social, Genetic and Developmental Psychiatry (SGDP) centre, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Asherson
mesh_terms: D000367:Age Factors; D000818:Animals; D031204:Caloric Restriction / Q000009:adverse effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics; D046228:Microarray Analysis; D009538:Nicotine / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D059467:Transcriptome
chemical_list: D009538:Nicotine