In Vivo Structural and Functional Abnormalities of the Striatums Is Related to Decreased Astrocytic BDNF in Itpr2-/- Mice Exhibiting Depressive-Like Behavior
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-/- mi...
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Wiley
2020-01-01
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Series: | Neural Plasticity |
Online Access: | http://dx.doi.org/10.1155/2020/8830670 |
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author | Shanmei Zeng Kai Liu Jingyu Zhang Chunhui Chen Yihua Xu Yulan Wu Yanjia Deng Xuegang Sun Ge Wen Linlin Jing |
author_facet | Shanmei Zeng Kai Liu Jingyu Zhang Chunhui Chen Yihua Xu Yulan Wu Yanjia Deng Xuegang Sun Ge Wen Linlin Jing |
author_sort | Shanmei Zeng |
collection | DOAJ |
description | 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. |
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institution | Kabale University |
issn | 2090-5904 1687-5443 |
language | English |
publishDate | 2020-01-01 |
publisher | Wiley |
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series | Neural Plasticity |
spelling | doaj-art-f1846cefd05f4436aff886eb918c7eac2025-02-03T00:58:44ZengWileyNeural Plasticity2090-59041687-54432020-01-01202010.1155/2020/88306708830670In Vivo Structural and Functional Abnormalities of the Striatums Is Related to Decreased Astrocytic BDNF in Itpr2-/- Mice Exhibiting Depressive-Like BehaviorShanmei Zeng0Kai Liu1Jingyu Zhang2Chunhui Chen3Yihua Xu4Yulan Wu5Yanjia Deng6Xuegang Sun7Ge Wen8Linlin Jing9NanFang Hospital, Southern Medical University, Guangzhou, ChinaNanFang Hospital, Southern Medical University, Guangzhou, ChinaNanFang Hospital, Southern Medical University, Guangzhou, ChinaThe Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaNanFang Hospital, Southern Medical University, Guangzhou, ChinaNanFang Hospital, Southern Medical University, Guangzhou, ChinaThe Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaNanFang Hospital, Southern Medical University, Guangzhou, ChinaIntegrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, ChinaBackground. 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.http://dx.doi.org/10.1155/2020/8830670 |
spellingShingle | Shanmei Zeng Kai Liu Jingyu Zhang Chunhui Chen Yihua Xu Yulan Wu Yanjia Deng Xuegang Sun Ge Wen Linlin Jing In Vivo Structural and Functional Abnormalities of the Striatums Is Related to Decreased Astrocytic BDNF in Itpr2-/- Mice Exhibiting Depressive-Like Behavior Neural Plasticity |
title | In Vivo Structural and Functional Abnormalities of the Striatums Is Related to Decreased Astrocytic BDNF in Itpr2-/- Mice Exhibiting Depressive-Like Behavior |
title_full | In Vivo Structural and Functional Abnormalities of the Striatums Is Related to Decreased Astrocytic BDNF in Itpr2-/- Mice Exhibiting Depressive-Like Behavior |
title_fullStr | In Vivo Structural and Functional Abnormalities of the Striatums Is Related to Decreased Astrocytic BDNF in Itpr2-/- Mice Exhibiting Depressive-Like Behavior |
title_full_unstemmed | In Vivo Structural and Functional Abnormalities of the Striatums Is Related to Decreased Astrocytic BDNF in Itpr2-/- Mice Exhibiting Depressive-Like Behavior |
title_short | In Vivo Structural and Functional Abnormalities of the Striatums Is Related to Decreased Astrocytic BDNF in Itpr2-/- Mice Exhibiting Depressive-Like Behavior |
title_sort | in vivo structural and functional abnormalities of the striatums is related to decreased astrocytic bdnf in itpr2 mice exhibiting depressive like behavior |
url | http://dx.doi.org/10.1155/2020/8830670 |
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