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      Nicotine and cigarette smoke modulate Nrf2-BDNF-dopaminergic signal and neurobehavioral disorders in adult rat cerebral cortex.

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          Abstract

          Nicotine and cigarette smoking (CS) are associated with addiction behavior, drug-seeking, and abuse. However, the mechanisms that mediate this association especially, the role of brain-derived neurotrophic factor (BDNF), dopamine (DA), and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling in the cerebral cortex, are not fully known. Therefore, we hypothesized that overexpression of BDNF and DA, and suppression of Nrf2 contribute to several pathological and behavioral alterations in adult cerebral cortex. Methodology/Principal Observations: We treated Wistar rats with different doses of oral nicotine and passive CS for 4-week (short-term) and 12-week (long-term) duration, where doses closely mimic the human smoking scenario. Our result showed dose-dependent association of anxiogenic and depressive behavior, and cognitive interference with neurodegeneration and DNA damage in the cerebral cortex upon exposure to nicotine/CS as compared to the control. Further, the results are linked to upregulation of oxidative stress, overexpression of BDNF, DA, and DA marker, tyrosine hydroxylase (TH), with concomitant downregulation of ascorbate and Nrf2 expression in the exposed cerebral cortex when compared with the control.

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          Author and article information

          Journal
          Hum Exp Toxicol
          Human & experimental toxicology
          SAGE Publications
          1477-0903
          0960-3271
          May 2018
          : 37
          : 5
          Affiliations
          [1 ] DN Gandhi: Former scientist & Head, NBT Div., ICMR-NIOH.
          Article
          10.1177/0960327117698543
          28641491
          fa5a2df6-a348-4338-9713-e1a0eb1f7837
          History

          Nicotine,BDNF,oxidative stress,molecular mechanism,dopamine,cigarette smoking,cerebral cortex behavior,Nrf2

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