Nicotine and cigarette smoke modulate Nrf2-BDNF-dopaminergic signal and neurobehavioral disorders in adult rat cerebral cortex#
| Autor: | DN Gandhi, AK Gautam, J Ravi Prakash, Nibedita Naha |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Nicotine medicine.medical_specialty NF-E2-Related Factor 2 Dopamine Health Toxicology and Mutagenesis media_common.quotation_subject Toxicology 03 medical and health sciences 0302 clinical medicine Neurotrophic factors Smoke Internal medicine Tobacco medicine Animals Rats Wistar media_common Cerebral Cortex Behavior Animal business.industry Brain-Derived Neurotrophic Factor Addiction Neurodegeneration Dopaminergic General Medicine medicine.disease 030104 developmental biology medicine.anatomical_structure Endocrinology Anxiogenic Cerebral cortex Anesthesia Tobacco Smoke Pollution business 030217 neurology & neurosurgery Signal Transduction medicine.drug |
| Zdroj: | Human & Experimental Toxicology. 37:540-556 |
| ISSN: | 1477-0903 0960-3271 |
| DOI: | 10.1177/0960327117698543 |
| Popis: | Background: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.Conclusion/Significance:Overall, our data strongly suggest that the intervention of DA and BDNF, and depletion of antioxidants are important factors during nicotine/CS-induced cerebral cortex pathological changes leading to neurobehavioral impairments, which could underpin the novel therapeutic approaches targeted at tobacco smoking/nicotine’s neuropsychological disorders including cognition and drug addiction. |
| Databáze: | OpenAIRE |
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