Nuclear respiratory factor-2α and adenosine triphosphate synapses in rat primary cortical neuron cultures: The key role of adenosine monophosphate-activated protein kinase.

Nuclear respiratory factor‑2α (NRF‑2α) is an important transcription factor that regulates mitochondrial oxidative phosphorylation and regeneration. NRF‑2α regulates mitochondrial transcription factors (mTF)A and B, and mitochondrial DNA by indirectly regulating the mitochondrial respiratory enzyme chain subunit. In addition, NRF‑2α is involved in the mitochondrial energy metabolism. Peroxisome proliferator‑activated receptor γ coactivator 1α (PGC‑1α), is an important transcription coactivator of NRF‑2α. Adenosine monophosphate‑activated protein kinase (AMPK) is considered an important effector in the regulation of the energy metabolism balance of nervous system microenvironments. However, the signaling mechanism underlying the energy coupling of PGC‑1α and NRF‑2α in visual cortical neurons remains to be elucidated. The present study used a primary culture system of rat visual cortical neurons in order to investigate whether AMPK is involved in the regulation of NRF‑2α and PGC‑1α expression in cortical neurons. The results of the present study indicated that KCl depolarization rapidly activated AMPK, and significantly increased the expression levels of PGC‑1α, NRF‑2α and mtTFA, as well as adenosine triphosphate production in cultured neurons. Similarly, the AMPK agonists 5‑aminoimidazole‑4‑carboxamide riboside and resveratrol significantly increased the mRNA expression levels of PGC‑1α and NRF‑2α in cultured neurons. These responses were blocked by compound C, an AMPK inhibitor. In conclusion, AMPK is an important transcriptional regulator of the neuronal excitation response, and exerts its regulatory effects via the PGC‑1α/NRF‑2α signaling pathway.