دانلود رایگان مقاله اثرات آمفتامین حاد بر Nurr1 و NF-kB P65 در ناحیه تگمنتوم شکمی

Abstract

Dopamine neurons are overstimulated by drugs of abuse and suffer molecular alterations that lead to addiction behavior. Nurr1 is a transcription factor crucial for dopamine neurons survival and dopamine production, activating the transcription of key genes like tyrosine hydroxylase (TH). Interestingly, nuclear factor-kappa B (NF-κB) has emerged as a new Nurr1 partner in response to inflammatory stimulus. In this study we evaluated the effects of single and repeated amphetamine administration in the expression of Nurr1 and the NF-κB p65 subunit in the rat ventral tegmental area (VTA). We found that acute amphetamine treatment increased Nurr1, p65 and TH protein levels in the VTA. On the other hand, chronic amphetamine treatment decreased Nurr1 and p65 protein levels, but TH was unchanged. Mammalian reporter assays in cell lines showed that p65 represses Nurr1 transcriptional activity in an artificial promoter driven by Nurr1 response elements and in the native rat TH promoter. These results indicate that Nurr1 and NF-κB p65 factors are involved in the adaptive response of dopamine neurons to psychostimulants and that both transcription factors could be regulating Nurr1- dependent transactivation in the VTA.

4.8. Statistical Analysis

Results are expressed as mean ± S.E.M. from at least three independent assays. Quantification analyses were performed using the ImageJ software. Statistical analyses were performed by means of the unpaired Student's t test (for two groups analyses) or one-way analysis of variance (ANOVA) followed by Tukey's post-test (for multiple group analyses), using the GraphPad Prism v5.0 software (San Diego, CA). A value of p < 0.05 was considered significant.