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...

Full description

Saved in:
Bibliographic Details
Main Authors: Shanmei Zeng, Kai Liu, Jingyu Zhang, Chunhui Chen, Yihua Xu, Yulan Wu, Yanjia Deng, Xuegang Sun, Ge Wen, Linlin Jing
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2020/8830670
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832568609797308416
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.
format Article
id doaj-art-f1846cefd05f4436aff886eb918c7eac
institution Kabale University
issn 2090-5904
1687-5443
language English
publishDate 2020-01-01
publisher Wiley
record_format Article
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
work_keys_str_mv AT shanmeizeng invivostructuralandfunctionalabnormalitiesofthestriatumsisrelatedtodecreasedastrocyticbdnfinitpr2miceexhibitingdepressivelikebehavior
AT kailiu invivostructuralandfunctionalabnormalitiesofthestriatumsisrelatedtodecreasedastrocyticbdnfinitpr2miceexhibitingdepressivelikebehavior
AT jingyuzhang invivostructuralandfunctionalabnormalitiesofthestriatumsisrelatedtodecreasedastrocyticbdnfinitpr2miceexhibitingdepressivelikebehavior
AT chunhuichen invivostructuralandfunctionalabnormalitiesofthestriatumsisrelatedtodecreasedastrocyticbdnfinitpr2miceexhibitingdepressivelikebehavior
AT yihuaxu invivostructuralandfunctionalabnormalitiesofthestriatumsisrelatedtodecreasedastrocyticbdnfinitpr2miceexhibitingdepressivelikebehavior
AT yulanwu invivostructuralandfunctionalabnormalitiesofthestriatumsisrelatedtodecreasedastrocyticbdnfinitpr2miceexhibitingdepressivelikebehavior
AT yanjiadeng invivostructuralandfunctionalabnormalitiesofthestriatumsisrelatedtodecreasedastrocyticbdnfinitpr2miceexhibitingdepressivelikebehavior
AT xuegangsun invivostructuralandfunctionalabnormalitiesofthestriatumsisrelatedtodecreasedastrocyticbdnfinitpr2miceexhibitingdepressivelikebehavior
AT gewen invivostructuralandfunctionalabnormalitiesofthestriatumsisrelatedtodecreasedastrocyticbdnfinitpr2miceexhibitingdepressivelikebehavior
AT linlinjing invivostructuralandfunctionalabnormalitiesofthestriatumsisrelatedtodecreasedastrocyticbdnfinitpr2miceexhibitingdepressivelikebehavior