Nagasawa Mao, Ikeda Hiromi, Kawase Takahiro, Iwamoto Ayaka, Yasuo Shinobu, Furuse Mitsuiro
Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 812-8581, Japan.
Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 812-8581, Japan.
Brain Res. 2015 Oct 22;1624:208-213. doi: 10.1016/j.brainres.2015.07.043. Epub 2015 Aug 1.
We previously reported that Wistar Kyoto rats, an animal model of depression, have a characteristically abnormal serine metabolism in the brain, i.e., lower serine and cystathionine, which is a metabolite of serine, concentrations in the brain. To explore the mechanism underlying this abnormality, the expression of cystathionine β-synthase and serine racemase, which are the enzymes involved in the serine metabolism, was investigated in the cerebellum and hippocampus of Wistar and Wistar Kyoto rats. Wistar Kyoto rats exhibited a significantly lower mRNA expression of cystathionine β-synthase in the cerebellum in comparison with Wistar rats, while expression levels in the hippocampus did not differ between strains. Previous study indicated that the reduction of cystathionine β-synthase in the brain induced cerebellar aplasia in mice. Therefore, the cerebellar size was compared between Wistar rats and Wistar Kyoto rats. Wistar Kyoto rats displayed a lower ratio of cerebellum weight to whole-brain weight compared with Wistar rats of the same generation or similar body weight, suggesting that Wistar Kyoto rats exhibit smaller cerebellum. These results suggest that the lower mRNA expression of cystathionine β-synthase in the cerebellum and the smaller size of cerebellum may be related to the depression-like behavior in Wistar Kyoto rats.
我们之前报道过,作为抑郁症动物模型的Wistar Kyoto大鼠大脑中丝氨酸代谢存在特征性异常,即大脑中丝氨酸及其代谢产物胱硫醚的浓度较低。为探究这种异常背后的机制,我们研究了Wistar大鼠和Wistar Kyoto大鼠小脑和海马中参与丝氨酸代谢的酶——胱硫醚β-合酶和丝氨酸消旋酶的表达。与Wistar大鼠相比,Wistar Kyoto大鼠小脑中胱硫醚β-合酶的mRNA表达显著降低,而两品系大鼠海马中的表达水平没有差异。先前的研究表明,大脑中胱硫醚β-合酶的减少会导致小鼠小脑发育不全。因此,我们比较了Wistar大鼠和Wistar Kyoto大鼠的小脑大小。与同代或体重相似的Wistar大鼠相比,Wistar Kyoto大鼠的小脑重量与全脑重量之比更低,这表明Wistar Kyoto大鼠的小脑较小。这些结果表明,小脑中胱硫醚β-合酶的mRNA表达降低以及小脑较小可能与Wistar Kyoto大鼠的抑郁样行为有关。