Carboni L, Carletti R, Tacconi S, Corti C, Ferraguti F
Department of Pharmacology, Glaxo Wellcome Medicines Research Centre, Verona, Italy.
Brain Res Mol Brain Res. 1998 Sep 18;60(1):57-68. doi: 10.1016/s0169-328x(98)00166-1.
MAPK pathways transduce a broad variety of extracellular signals into cellular responses. Despite their pleiotropic effects and their ubiquitous distribution, surprisingly little is known about their involvement in the communication network of nerve cells. As a first step to elucidate the role of MAPK pathways in neuronal signalling, we studied the distribution of SAPK alpha/JNK2, SAPK beta/JNK3, and SAPK gamma/JNK1, three isoforms of SAPK/JNK, a stress-activated MAPK subfamily. We compared the mRNA localisation of the three main isoforms in the adult and developing rat brain using in situ hybridisation. In the adult brain, SAPK alpha and beta were widely but heterogeneously distributed, reproducing the pattern of a probe that does not discriminate the isoforms. Differently, high labelling for the SAPK gamma probe was exclusively localised in the endopiriform nucleus and medial habenula. Intermediate staining was detected in the hippocampus. During post-natal development, SAPK beta showed the same localisation as in the adult. Nevertheless, the semi-quantitative analysis of optical densities showed significantly different mRNA levels. In the adult, SAPK gamma signal was weak, whereas in newborn rats the labelling was intense and widely distributed. SAPK gamma mRNA levels decreased during development, to reach the low signals detected in the adult. These results suggest that in the central nervous system SAPK-type MAP kinases perform significant physiological functions which are particularly relevant during post-natal development. The distinct distribution patterns of SAPK isoforms in the adult rat brain support the hypothesis that separate functions are performed by the products of the three SAPK genes.
丝裂原活化蛋白激酶（MAPK）信号通路可将多种细胞外信号转导为细胞应答。尽管它们具有多效性作用且分布广泛，但令人惊讶的是，对于它们在神经细胞通讯网络中的作用却知之甚少。作为阐明MAPK信号通路在神经元信号传导中作用的第一步，我们研究了应激活化蛋白激酶（SAPK）/JNK（一种应激激活的MAPK亚家族）的三种亚型，即SAPKα/JNK2、SAPKβ/JNK3和SAPKγ/JNK1的分布情况。我们使用原位杂交技术比较了这三种主要亚型在成年和发育中的大鼠脑中的mRNA定位。在成年脑中，SAPKα和β分布广泛但不均匀，呈现出一种无法区分亚型的探针的分布模式。不同的是，SAPKγ探针的高标记仅定位于内梨状核和内侧缰核。在海马体中检测到中等程度的染色。在出生后的发育过程中，SAPKβ的定位与成年时相同。然而，光密度的半定量分析显示mRNA水平存在显著差异。在成年大鼠中，SAPKγ信号较弱，而在新生大鼠中标记强烈且分布广泛。SAPKγ mRNA水平在发育过程中下降，直至达到成年时检测到的低信号水平。这些结果表明，在中枢神经系统中，SAPK型丝裂原活化蛋白激酶发挥着重要的生理功能，这些功能在出生后的发育过程中尤为重要。成年大鼠脑中SAPK亚型的不同分布模式支持了这样一种假设，即三个SAPK基因的产物执行着不同的功能。
