Current Progress in Molecular Responses to Acidosis in the Central Nervous System

The ventral medullary surface of the medulla oblongata is known as the site of the central chemosensitive neurons in humans. These neurons sense decrease in pH of the cerebrospinal fluid followed by hypercapnia (increased arterial CO2) and induce hyperventilation. Recently, several advances have been made in understanding central chemosensitivity at the molecular and cellular levels. Recent studies have identified several transcription factors such as c-Jun, c-Fos, FosB and small Maf proteins that may play critical roles in the brain adaptation to hypercapnia. Hypercapnic stimulation also activates c-Jun NH2-terminal kinase (JNK) cascade via influx of extracellular Ca2+ through voltage-gated Ca2+ channels. In addition, several transmembrane proteins including Rhombex-29 (rhombencephalic expression protein-29 kDa) and Past-A (proton-associated sugar transporter-A) have been implicated in regulation of H+ sensitivity and brain acidosismediated energy metabolism, respectively. These novel discoveries may provide new insights into the design for new drugs and understanding of neurological disorders. This review focuses on the properties of genes stimulated by acidosis in response to hypercapnia and discusses current knowledge on the molecular basis of neuronal regulation during acidosis.