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Nicotine Restores Wt-Like Levels of Reelin and GAD67 Gene Expression in Brain of Heterozygous Reeler Mice

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Abstract

Important reduction of reelin, a neural development- and plasticity-associated protein, and glutamic acid decarboxylase (GAD67) are reported in brains of schizophrenic patients. These individuals are consistently engaged in tobacco smoking and nicotine is thought to alleviate negative behavioral symptoms or cognitive alterations. In mouse brain, nicotine has been shown to reduce GAD67 promoter methylation and increase its transcription. We assessed the effects of administration of nicotine (1 mg/kg s.c.) for 6 days, in male mice heterozygous for reelin (HRM), a putative model for symptoms related to schizophrenia. Expression of reelin, GAD67 and brain-derived neurotrophic factor (BDNF) was measured in different brain areas. RNA expression analysis evidenced genotype-related changes, with a marked reduction in reelin and GAD67 gene expression in prefrontal cortex, hippocampus, cerebellum, and striatum from HRM. Nicotine treatment selectively reversed the HRM-related phenotype in most brain areas and increased BDNF gene expression in cortex and hippocampus of both genotypes. Locomotor performance in their home cage revealed that HRM subjects were characterized by general hyperactivity; with nicotine administration restoring WT-like levels of locomotion. These findings are interpreted within the hypothesis of pre-existing vulnerability (based on haploinsufficiency of reelin) to brain and behavioral disorders and regulative effects associated with nicotine exposure.

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Acknowledgments

This research was supported by IRE-IFO (RF2008) “MECP2 phosphorylation and related kinase in Rett syndrome” to GL and by Italian ministry of health, with “under 40” young-investigator project “ADHD-sythe” to Walter Adriani. We are grateful to Luigia Cancemi for animal care.

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The authors declare no conflict of interest.

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  1. Section of Behavioural Neuroscience, Department of Cell Biology & Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy

    Emilia Romano & Giovanni Laviola

  2. Section of Neuroscience, Department of Psychology, Sapienza University of Rome, Rome, Italy

    Andrea Fuso

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  1. Emilia Romano
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  2. Andrea Fuso
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  3. Giovanni Laviola
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Correspondence to Giovanni Laviola.

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Romano, E., Fuso, A. & Laviola, G. Nicotine Restores Wt-Like Levels of Reelin and GAD67 Gene Expression in Brain of Heterozygous Reeler Mice. Neurotox Res 24, 205–215 (2013). https://doi.org/10.1007/s12640-013-9378-3

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