nrf1 and nrf2 knockdown effect in anxiety-related behavior and mitochondrial function

Introduction: nuclear factor, erythroid-derived 2, -like2 (nrf2) and nuclear erythroid 2-related factor 1 (nrf1) stand as two important regulators of antioxidant defense system. materials and methods: small interfering rna (sirna) targeting nrf1 and nrf2 (nrf1&2) was injected in dorsal third ventricle of adult male albino wistar rats. anxiety-related behaviors and protein level of mitochondrial biogenesis, apoptotic marker factors and also electron transport chain (etc), citrate synthase (cs) and malate dehydrogenase (mdh) enzymes activity in three brain regions: hippocampus, prefrontal cortex, and amygdala were evaluated. results: nrf1&2-silenced rats induced anxiety-like behaviors compared to the control group. the level of peroxisome proliferator- activated receptor gamma coactivator 1-alpha (pgc-1α) protein increased in those three regions. although nrf1&2-silencing decreased mdh activity in hippocampus and prefrontal cortex, the activity of cs was increased in all three mentioned areas. however, nrf1&2 silencing had no effect in complex i and ii-iii activity, but complex iv activity was increased, particularly in amygdala. furthermore, bax/bcl_2 ratio and cleavage of caspase-3 was increased in all mentioned areas of the brain in nrf1&2-silenced group. conclusion: in conclusion, the presented data evaluated the complexity of mitochondrial functions and nrf1 and nrf2 in rat’s brain and points to mitochondrial crucial role in oxidative stress, energy metabolism, and behavior.