Co‐localization of phosphorylated extracellular signal‐regulated protein kinases 1/2 (ERK1/2) and phosphorylated eukaryotic initiation factor 2α (eIF2α) in response to a threonine‐devoid diet

The anterior piriform cortex (APC) has been shown to be an essential brain structure for the detection of dietary indispensable amino acid (IAA) deficiency, but little has been known about possible molecular detection mechanisms. Increased phosphorylation of the α-subunit of the eukaryotic initiation factor 2α (eIF2α) has been directly linked to amino acid deficiency in yeast. Recently, we have shown increased phosphorylation of eIF2α (p-eIF2α) in the rat APC 20 minutes after ingestion of an IAA-deficient meal. We suggest that if phosphorylation of eIF2α is an important mechanism in detection of IAA deficiency, then APC neurons that show p-eIF2α should also show molecular evidence of potentiation. The present research demonstrates increased expression and co-localization of p-eIF2α and phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) in APC neurons, but not in the primary motor or agranular insular cortices in response to an IAA-deficient diet. ERK1/2 is an element of the mitogen-activated protein kinase cascade, an intraneuronal signaling mechanism associated with neuronal activation. The region of the APC that responds to IAA deficiency with increased p-eIF2α and p-ERK1/2 labeling ranges from 3.1 to 2.5 mm rostral of bregma. Within this region, only a few neurons respond to IAA deficiency with co-localization of abundant p-eIF2α and p-ERK1/2. These chemosensory neurons probably detect IAA deficiency and generate neuronal signaling to other portions of the brain, changing feeding behavior. J. Comp. Neurol. 494:485–494, 2006. © 2005 Wiley-Liss, Inc.