Castellano Stefania, Macchi Francesca, Scali Manuela, Huang Josh Z, Bozzi Yuri
Istituto di Neuroscienze del C.N.R., via Moruzzi 1, 56100 Pisa, Italy.
Brain Res. 2006 Sep 7;1108(1):12-8. doi: 10.1016/j.brainres.2006.06.012. Epub 2006 Jul 7.
Branched chain aminotransferase (BCAT) catalyzes the transamination of the essential branched chain amino acids (leucine, isoleucine and valine) with alpha-ketoglutarate. BCAT exists in two isoforms: one cytosolic (BCATc), mainly expressed in the nervous system, and the other mitochondrial (BCATm), present in a greater number of tissues. We previously showed that BCATc mRNA and protein expression in the dorsal lateral geniculate nucleus of the thalamus is up-regulated by exogenous administration of brain-derived neurotrophic factor (BDNF) following lesion of the visual cortex in newborn rats. Here, we analyzed the expression of BCATc mRNA in the brain of transgenic mice overexpressing the rat BDNF cDNA under the control of the alpha-calcium/calmodulin-dependent kinase II (alphaCaMKII) promoter. In these animals, BDNF is overexpressed in the telencephalon starting from the second postnatal week. RT-PCR and in situ hybridization experiments showed that BCATc mRNA is overexpressed in restricted regions of the cerebral cortex (parietal area) and hippocampus (hilus and CA3 pyramidal cell layer) of adult BDNF transgenic mice respect to wild-type animals. These differences between wt and BDNF mice were not detected in animals of 1 week of age. These results demonstrate that the expression of the BCATc gene in the brain is specifically regulated by BDNF in a time- and region-dependent fashion.
支链氨基酸转氨酶（BCAT）催化必需支链氨基酸（亮氨酸、异亮氨酸和缬氨酸）与α-酮戊二酸之间的转氨基作用。BCAT存在两种同工型：一种是胞质型（BCATc），主要在神经系统中表达；另一种是线粒体型（BCATm），存在于更多组织中。我们之前发现，新生大鼠视觉皮层损伤后，脑源性神经营养因子（BDNF）的外源性给药可上调丘脑背外侧膝状核中BCATc的mRNA和蛋白表达。在此，我们分析了在α-钙/钙调蛋白依赖性激酶II（αCaMKII）启动子控制下过表达大鼠BDNF cDNA的转基因小鼠脑中BCATc mRNA的表达。在这些动物中，从出生后第二周开始，BDNF在端脑中过表达。逆转录聚合酶链反应（RT-PCR）和原位杂交实验表明，与野生型动物相比，成年BDNF转基因小鼠大脑皮层（顶叶区域）和海马体（门区和CA3锥体细胞层）的特定区域中BCATc mRNA过表达。在1周龄的动物中未检测到野生型和BDNF小鼠之间的这些差异。这些结果表明，大脑中BCATc基因的表达受到BDNF以时间和区域依赖性方式的特异性调控。
