Nrf2 deficiency leads to behavioral, neurochemical and transcriptional changes in mice.

Nrf2 is a transcription factor that regulates the antioxidant and detoxification enzyme genes and provides defense against oxidative and electrophilic stresses in various tissues. In brain, while neuroprotective functions of Nrf2 have been well documented, Nrf2 contribution to the brain function remains to be elucidated. To address this issue, we investigated whether Nrf2 deficiency affects psychological behaviors, neurotransmitter systems and gene expressions in mice. We conducted four behavioral tests, social interaction, open-field, rotarod and forced swimming tests and found that Nrf2 knockout mice exhibited reduced immobility in the forced swimming test. Neurochemical analyses revealed that the dopamine and serotonin metabolites increased in the brains of Nrf2 knockout mice. We also present a catalog of genes whose expression is Nrf2-dependent in brain under unstressed conditions, which includes a number of xenobiotic-metabolizing enzyme genes. These results thus support our contention that Nrf2 regulates its target genes in brain under unstressed conditions and loss of Nrf2 affects various brain functions.