Acute nitrogen dioxide inhalation induces mitochondrial dysfunction in rat brain

• Acute NO2 inhalation stimulated ROS generation in rat brain.
• Acute NO2 exposure altered mitochondrial ultrastructure.
• Acute NO2 inhalation impaired mitochondrial respiratory function.
• Acute NO2 exposure repressed mitochondrial biogenesis.

Recent epidemiological literatures imply that NO2 is a potential risk factor of neurological disorders. Whereas, the pathogenesis of various neurological diseases has been confirmed correlate to mitochondrial dysfunction, and mitochondria play the crucial roles in energy metabolism, free radicals production and apoptosis triggering in response to neuronal injury. Therefore, to clarify the possible mechanisms for NO2-induced neurotoxicity, in the present study, we investigated the possible effects of acute NO2 inhalation (5, 10 and 20 mg/m3 with 5 h/day for 7 days) on energy metabolism and biogenesis in rat cortex, mainly including mitochondrial ultrastructure, mitochondrial membrane potential, cytochrome c oxidase activity, cytochrome c oxidase (CO) and ATP synthase subunits, ATP content, and transcription factors. The results showed that NO2 exposure induced mitochondrial morphological changes in rat cortex, and the alteration was coupled with the abnormality of mitochondrial energy metabolism, including decreased respiratory complexes, reduced ATP production and increased production of ROS. Also, increased ROS in turn caused mitochondrial membrane damage, energy production defect and mitochondrial biogenesis inhibition. It suggests the significantly damaged mitochondrial energy metabolism and impaired biogenesis in rat brain after NO2 exposure, and provides a new understanding of the pathophysiological mechanisms of NO2-induced neurological disorders.