| First Author | Pacchioni AM | Year | 2007 |
| Journal | Brain Res | Volume | 1127 |
| Issue | 1 | Pages | 26-35 |
| PubMed ID | 17113054 | Mgi Jnum | J:116598 |
| Mgi Id | MGI:3694565 | Doi | 10.1016/j.brainres.2006.10.036 |
| Citation | Pacchioni AM, et al. (2007) Nrf2 gene deletion fails to alter psychostimulant-induced behavior or neurotoxicity. Brain Res 1127(1):26-35 |
| abstractText | The transcription factor NF-E2-related factor (Nrf2) regulates the induction of phase 2 detoxifying enzymes by oxidative stress, including synthesis of the catalytic subunit (xCT) of the heterodimeric cystine-glutamate exchanger (system xc-). Repeated cocaine treatment in rats causes persistent neuroadaptations in glutamate neurotransmission in the nucleus accumbens that result, in part, from reduced activity of system xc-. Since in vitro under- or over-expression of Nrf2 regulates system xc- activity and xCT content, it was hypothesized that in vivo deletion of the Nrf2 gene would: 1) decrease system xc- activity, 2) produce a behavioral phenotype resembling that elicited by chronic cocaine administration, and 3) enhance dopamine depletion after methamphetamine-induced oxidative stress. In all three experiments no genotypic difference was measured between mice sustaining homozygous Nrf2 gene deletion and wild-type littermates. Thus, while Nrf2 is a transcriptional regulator of xCT and capable of protecting cells from oxidative stress, following Nrf2 gene deletion this role can be partially compensated by other mechanisms and methamphetamine-induced oxidative stress and dopamine toxicity does not significantly involve Nrf2. |
