Low-Moderate Doses of Nicotine Decreased mRNA of NGF and BDNF and Their Receptors at 30 Min in the Frontal Cortex and Hippocampus of ApoE-KO Mice

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Background: Several studies have detected nicotine-associated increases in the mRNA and protein expression of NGF, BDNF and TrkA and TrkB receptors in multiple brain regions. Methods: We investigated the acute effects of different doses of nicotine (0.1, 0.5 and 1.0 mg/kg) on the mRNA levels of NGF, BDNF, TrkA and TrkB in the frontal cortex and hippocampus of ApoE-knockout (ApoE-KO) and wild-type (WT) mice. Results: The results demonstrated that in the frontal cortex and hippocampus, nicotine decreases NGF and BDNF mRNA levels in both ApoE-KO and WT mice. Nicotine also reduced TrkA in the frontal cortex and TrkB in both brain regions of WT mice, whereas no changes were observed in ApoE-KO mice. Interestingly, all of these effects were limited to low-intermediate doses (0.1 and 0.5 mg/kg) of nicotine, while 1.0 mg/kg of nicotine had no noticeable effect on the brain of either strain of mice. ApoE-KO mice showed a distinctly higher level of NGF mRNA expression versus the WT mice in both regions of the brain, whereas TrkA expression was lower only in the frontal cortex. Conclusions: These findings suggest that acute nicotine causes a decrease in the mRNA levels of NGF, BDNF and their receptors in the frontal cortex and hippocampus of mice depending on nicotine doses. A high level of NGF mRNA was observed in the brain of ApoE-KO mice, suggesting a role of ApoE in the expressions of neurotrophins in the hippocampus. doi: http://dx.doi.org/10.4021/jnr217e