McNamara R K, Lenox R H
Department of Psychiatry, University of Florida College of Medicine, Gainesville 32610-0256, USA.
J Comp Neurol. 1997 Mar 3;379(1):48-71.
Myristoylated alanine-rich C-kinase substrate (MARCKS) and F1/GAP-43 (B-50/neuromodulin) are both major specific substrates for protein kinase C (PKC) and appear to play an important role in the regulation of neuroplastic events during development and in the adult brain. Since PKC isozymes are differentially expressed in brain and the expression of F1/GAP-43 and MARCKS are differentially regulated by PKC through posttranslational mechanisms, the present study examined the relative distribution of both mRNAs in the adult brain by using in situ hybridization histochemistry. MARCKS hybridization was most pronounced in the olfactory bulb, piriform cortex (layer II), medial habenular nucleus, subregions of the amygdala, specific hypothalamic nuclei, hippocampal granule cells, neocortex, and cerebellar cortex, intermediate in the superior colliculus, hippocampal CA1, and certain brainstem nuclei including the locus coeruleus, and low-absent in regions of the caudate-putamen, geniculate, thalamic nuclei, lateral habenular nucleus, and hippocampal CA3 pyramidal and hilar neurons. Consistent with previous reports, prominent F1/GAP-43 hybridization was observed in neocortex, medial geniculate, piriform cortex (layer II), substantia nigra pars compacta, hippocampal CA3 pyramidal cells, thalamic and hypothalamic nuclei, lateral habenular nucleus, locus coeruleus, raphe nuclei, and cerebellar granule cells, intermediate in regions of the thalamus, hypothalamus, and amygdala, and low-absent in regions of the olfactory bulb, caudate-putamen, medial habenular nucleus, hippocampal granule cells, and superior colliculus. Overall, F1/GAP-43 was highly expressed in a greater number of regions compared to MARCKS and, in a number of regions, including the hippocampus, habenular complex, ventral tegmentum, geniculate, and certain brain stem nuclei, a striking inverse pattern of expression was observed. These results indicate that MARCKS gene expression, like that of F1/GAP-43, remains elevated in select regions of the adult rat brain which are associated with a high degree of retained plasticity. The potential role of PKC in the regulation of MARCKS and F1/GAP-43 gene expression in brain is assessed.
豆蔻酰化富含丙氨酸的蛋白激酶C底物（MARCKS）和F1/GAP-43（B-50/神经调节蛋白）均为蛋白激酶C（PKC）的主要特异性底物，且似乎在发育过程及成体大脑中神经可塑性事件的调节中发挥重要作用。由于PKC同工酶在脑中呈差异表达，且F1/GAP-43和MARCKS的表达通过翻译后机制受到PKC的差异调节，故本研究采用原位杂交组织化学方法检测了二者mRNA在成体大脑中的相对分布。MARCKS杂交信号在嗅球、梨状皮质（II层）、内侧缰核、杏仁核亚区、特定下丘脑核团、海马颗粒细胞、新皮质和小脑皮质最为明显，在上丘、海马CA1以及包括蓝斑在内的某些脑干核团中信号强度中等，而在尾状核-壳核、膝状体、丘脑核团、外侧缰核以及海马CA3锥体细胞和齿状回神经元区域信号强度低或无信号。与先前报道一致，在新皮质、内侧膝状体、梨状皮质（II层）、黑质致密部、海马CA3锥体细胞、丘脑和下丘脑核团、外侧缰核、蓝斑、中缝核以及小脑颗粒细胞中观察到明显的F1/GAP-43杂交信号，在丘脑、下丘脑和杏仁核区域信号强度中等，而在嗅球、尾状核-壳核、内侧缰核、海马颗粒细胞和上丘区域信号强度低或无信号。总体而言，与MARCKS相比，F1/GAP-43在更多区域高表达，且在包括海马、缰核复合体、腹侧被盖区、膝状体以及某些脑干核团在内的多个区域观察到显著的反向表达模式。这些结果表明，与F1/GAP-43一样，MARCKS基因表达在成年大鼠大脑的特定区域中仍保持升高，这些区域与高度保留的可塑性相关。文中评估了PKC在调节脑中MARCKS和F1/GAP-43基因表达中的潜在作用。
