Important reduction of reelin, a neural devel- opment- and plasticity-associated protein, and glutamic acid decarboxylase (GAD67) are reported in brains of schizo- phrenic 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 schizo- phrenia. 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 hippocam- pus 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 vulnera- bility (based on haploinsufficiency of reelin) to brain and behavioral disorders and regulative effects associated with nicotine exposure.

Nicotine Restores Wt-Like Levels of Reelin and GAD67 Gene Expression in Brain of Heterozygous Reeler Mice / Emilia Romano;Andrea Fuso;Giovanni Laviola. - In: NEUROTOXICITY RESEARCH. - ISSN 1029-8428. - ELETTRONICO. - (2013), pp. ---. [10.1007/s12640-013-9378-3]

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

ROMANO, EMILIA;
2013

Abstract

Important reduction of reelin, a neural devel- opment- and plasticity-associated protein, and glutamic acid decarboxylase (GAD67) are reported in brains of schizo- phrenic 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 schizo- phrenia. 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 hippocam- pus 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 vulnera- bility (based on haploinsufficiency of reelin) to brain and behavioral disorders and regulative effects associated with nicotine exposure.
2013
-
-
Emilia Romano;Andrea Fuso;Giovanni Laviola
File in questo prodotto:
File Dimensione Formato  
Romano 2013.pdf

Accesso chiuso

Tipologia: Altro
Licenza: Tutti i diritti riservati
Dimensione 759.57 kB
Formato Adobe PDF
759.57 kB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/806286
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 10
social impact