Hypothalamic transcriptome plasticity in two rodent species reveals divergent differential gene expression but conserved pathways

We have addressed the question of how different rodent species cope with the life-threatening homeostatic challenge of dehydration at the level of transcriptome modulation in the supraoptic nucleus (SON), a specialised hypothalamic neurosecretory apparatus responsible for the production of the antidiuretic peptide hormone arginine vasopressin (AVP). AVP maintains water balance by promoting water conservation at the level of the kidney. Dehydration evokes a massive increase in the regulated release of AVP from SON axon terminals located in the posterior pituitary, and this is accompanied by a plethora of changes in the morphology, electrophysiological properties, biosynthetic and secretory activity of this structure. Microarray analysis was used to generate a definitive catalogue of the genes expressed in the mouse SON, and to describe how the gene expression profile changes in response to dehydration. Comparison of the genes differentially expressed in the mouse SON as a consequence of dehydration with those of the rat has revealed many similarities, pointing to common processes underlying the function-related plasticity in this nucleus. In addition we have identified many genes that are differentially expressed in a species-specific manner. However, in many cases, we have found that the hyperosmotic cue can induce species-specific alterations in the expression of different genes in the same pathway. The same functional end can be served by different means, via differential modulation, in different species, of different molecules in the same pathway. We suggest that pathways, rather than specific genes, should be the focus of integrative physiological studies based on transcriptome data.本研究围绕不同啮齿类动物如何通过视上核（supraoptic nucleus, SON）的转录组调控，应对脱水这一可危及生命的稳态挑战展开。视上核是一类特化的下丘脑神经分泌装置，负责合成抗利尿肽激素精氨酸加压素（arginine vasopressin, AVP）。AVP通过促进肾脏的水重吸收维持机体水平衡。脱水会引发垂体后叶内视上核轴突末梢的AVP调控性释放大幅增加，同时伴随该结构在形态、电生理特性、生物合成与分泌活性等方面的大量改变。本研究采用微阵列分析（Microarray analysis），构建了小鼠视上核的明确基因表达清单，并阐明了脱水刺激下小鼠视上核的基因表达谱变化情况。将脱水诱导的小鼠视上核差异表达基因与大鼠的同类数据进行比对后，本研究发现二者存在诸多共性，提示该核团功能相关可塑性的背后存在共同的调控机制。此外，本研究还鉴定出一批以物种特异性方式差异表达的基因。不过在多数情况下，高渗刺激可在同一通路的不同基因上诱导物种特异性的表达改变。不同物种可通过对同一通路内不同分子的差异化调控，采用不同途径实现相同的功能终点。本研究提出，基于转录组数据开展整合生理学研究时，应将通路而非单一特定基因作为研究焦点。