Background. Previous researches indicate that Itpr2^-/- mice (inositol 1,4,5-trisphosphate receptor type 2 knockout mice) show depressive-like symptoms; however, little is known regarding the in vivo neurobiological effect of Itpr2 as well as the specific pattern of brain abnormalities in Itpr2^-/- mice. Methods/Materials. First, behavioral tests, structural magnetic resonance imaging (MRI), and resting-state functional MRI were performed on Itpr2^-/- mice and matched healthy controls. Voxel-based morphometry and seed-based voxel-wise functional connectivity (FC) were, respectively, calculated to assess the gray matter volume and the functional activities of the brain in vivo. Second, the sample of relevant changed brain regions was extracted to detect the expression of BDNF. Finally, to further validate the relationship between Itpr2 deficiency and the observed brain abnormalities, we performed Western blotting to detect the expression of pro-BDNF and mBDNF in Itpr2^-/- C8-D1A (a type of astrocyte). Results. Compared with controls, Itpr2^-/- mice showed depressive-like behaviors as well as significantly lower gray matter volume in striatums mainly, periaqueductal GM, and the right frontoparietal cortices as well as lower striatal-hippocampal and striatal-right parietal cortex (mainly for the primary and secondary somatosensory cortex) FC. Moreover, decreased expression of mBDNF was found in both sample tissues of the striatum in Itpr2^-/- mice and Itpr2^-/- C8-D1A. Conclusion. By combining biochemistry and MR analyses, this study provides evidences to support that the Itpr2-related neuropathological effect is possibly mediated by the striatal abnormality associated with dysfunctional astrocytes in Itpr2^-/- mice in vivo, thus may help us better understand underlying mechanisms of Itpr2 deficiency as well as its relation to depressive-like behavior.

中文翻译：

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纹状体的体内结构和功能异常与 Itpr2-/- 小鼠表现出抑郁样行为的星形胶质细胞 BDNF 减少有关。

背景。之前的研究表明，Itpr2 ^-/-小鼠（肌醇1,4,5-三磷酸受体2型敲除小鼠）表现出抑郁样症状；然而，关于Itpr2 的体内神经生物学效应以及Itpr2 ^-/-小鼠脑异常的特定模式知之甚少。方法/材料。首先，对Itpr2进行了行为测试、结构磁共振成像（MRI）和静息态功能性MRI ^-/-小鼠和匹配的健康对照。分别计算基于体素的形态测量学和基于种子的体素功能连接 (FC) 以评估灰质体积和体内大脑的功能活动。其次，提取相关变化的大脑区域的样本以检测BDNF的表达。最后，为了进一步验证 Itpr2 缺乏与观察到的大脑异常之间的关系，我们进行了蛋白质印迹以检测Itpr2 ^-/- C8-D1A（一种星形胶质细胞）中 pro-BDNF 和 mBDNF 的表达。结果。与对照相比，Itpr2 ^-/-小鼠表现出抑郁样行为以及显着降低的灰质体积，主要是纹状体、导水管周围 GM、右额顶叶皮质以及下纹状体 - 海马和纹状体 - 右顶叶皮层（主要用于初级和次级体感皮层） FC . 此外，在Itpr2 ^-/-小鼠和Itpr2 ^-/- C8-D1A的纹状体样本组织中发现 mBDNF 的表达降低。结论。通过结合生物化学和 MR 分析，该研究提供证据支持 Itpr2 相关的神经病理学效应可能是由体内Itpr2 ^-/-小鼠中与功能失调的星形胶质细胞相关的纹状体异常介导的，因此可以帮助我们更好地理解 Itpr2 缺乏的潜在机制及其与抑郁样行为的关系。