Sharp James W, Ross-Inta Catherine M, Hao Shuzhen, Rudell J B, Gietzen Dorothy W
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, California 95616, USA.
J Comp Neurol. 2006 Jan 20;494(3):485-94. doi: 10.1002/cne.20817.
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 alpha-subunit of the eukaryotic initiation factor 2alpha (eIF2alpha) has been directly linked to amino acid deficiency in yeast. Recently, we have shown increased phosphorylation of eIF2alpha (p-eIF2alpha) in the rat APC 20 minutes after ingestion of an IAA-deficient meal. We suggest that if phosphorylation of eIF2alpha is an important mechanism in detection of IAA deficiency, then APC neurons that show p-eIF2alpha should also show molecular evidence of potentiation. The present research demonstrates increased expression and co-localization of p-eIF2alpha 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-eIF2alpha 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-eIF2alpha and p-ERK1/2. These chemosensory neurons probably detect IAA deficiency and generate neuronal signaling to other portions of the brain, changing feeding behavior.
前梨状皮质（APC）已被证明是检测膳食必需氨基酸（IAA）缺乏的重要脑结构，但对于可能的分子检测机制知之甚少。真核起始因子2α（eIF2α）α亚基的磷酸化增加已直接与酵母中的氨基酸缺乏相关联。最近，我们发现摄入缺乏IAA的食物20分钟后，大鼠APC中eIF2α（p-eIF2α）的磷酸化增加。我们认为，如果eIF2α的磷酸化是检测IAA缺乏的重要机制，那么显示p-eIF2α的APC神经元也应该显示出增强的分子证据。本研究表明，响应缺乏IAA的饮食，APC神经元中p-eIF2α和磷酸化细胞外信号调节蛋白激酶1/2（p-ERK1/2）的表达和共定位增加，但在初级运动皮质或无颗粒岛叶皮质中未出现这种情况。ERK1/2是丝裂原活化蛋白激酶级联反应的一个元件，是一种与神经元激活相关的神经元内信号传导机制。APC中对IAA缺乏作出反应且p-eIF2α和p-ERK1/2标记增加的区域位于前囟嘴侧3.1至2.5毫米之间。在该区域内，只有少数神经元对IAA缺乏作出反应，p-eIF2α和p-ERK1/2大量共定位。这些化学感觉神经元可能检测IAA缺乏，并向大脑其他部分产生神经元信号，从而改变进食行为。
