Analysis of Cerebral Small Vessel Changes in AD Model Mice
Amyloid β (Aβ) peptide is deposited in the brains of sporadic Alzheimer’s disease (AD) due to impaired vessel-dependent clearance. To understand the mechanisms, we investigated time-dependent cerebrovascular changes in AD model mice. Cerebrovascular and other pathological changes were analyzed in AD...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/11/1/50 |
| _version_ | 1797445724804218880 |
|---|---|
| author | Abu Zaffar Shibly Abdullah Md. Sheikh Makoto Michikawa Shatera Tabassum Abul Kalam Azad Xiaojing Zhou Yuchi Zhang Shozo Yano Atsushi Nagai |
| author_facet | Abu Zaffar Shibly Abdullah Md. Sheikh Makoto Michikawa Shatera Tabassum Abul Kalam Azad Xiaojing Zhou Yuchi Zhang Shozo Yano Atsushi Nagai |
| author_sort | Abu Zaffar Shibly |
| collection | DOAJ |
| description | Amyloid β (Aβ) peptide is deposited in the brains of sporadic Alzheimer’s disease (AD) due to impaired vessel-dependent clearance. To understand the mechanisms, we investigated time-dependent cerebrovascular changes in AD model mice. Cerebrovascular and other pathological changes were analyzed in AD model mice (J20 strain) aging from 2 to 9 months by immunostaining. At 2 months, Aβ was only intraneuronal, whereas vessels were positive from 3 months in J20 mice. Compared to wild-type (WT), vessel density was increased at 2 months but decreased at 9 months in J20 mice, claudin-5 levels were decreased, and vascular endothelial growth factor (VEGF) levels were increased in the cortex and hippocampus of J20 mice brain at all time points. Albumin extravasation was evident from 3 months in J20 brains. Collagen 4 was increased at 2 and 3 months. Aquaporin 4 was spread beyond the vessels starting from 3 months in J20, which was restricted around the vessel in wild-type mice. In conclusion, the study showed that an early decrease in claudin-5 was associated with VEGF expression, indicating dysfunction of the blood–brain barrier. Decreased claudin-5 might cause the leakage of blood constituents into the parenchyma that alters astrocyte polarity and its functions. |
| first_indexed | 2024-03-09T13:30:00Z |
| format | Article |
| id | doaj.art-2f30aa809c574cd29fd9703b5a6e4f66 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T13:30:00Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-2f30aa809c574cd29fd9703b5a6e4f662023-11-30T21:18:42ZengMDPI AGBiomedicines2227-90592022-12-011115010.3390/biomedicines11010050Analysis of Cerebral Small Vessel Changes in AD Model MiceAbu Zaffar Shibly0Abdullah Md. Sheikh1Makoto Michikawa2Shatera Tabassum3Abul Kalam Azad4Xiaojing Zhou5Yuchi Zhang6Shozo Yano7Atsushi Nagai8Department of Neurology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, JapanDepartment of Laboratory Medicine, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, JapanDepartment of Biochemistry, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, JapanDepartment of Laboratory Medicine, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, JapanDepartment of Neurology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, JapanDepartment of Neurology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, JapanDepartment of Neurology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, JapanDepartment of Laboratory Medicine, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, JapanDepartment of Neurology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, JapanAmyloid β (Aβ) peptide is deposited in the brains of sporadic Alzheimer’s disease (AD) due to impaired vessel-dependent clearance. To understand the mechanisms, we investigated time-dependent cerebrovascular changes in AD model mice. Cerebrovascular and other pathological changes were analyzed in AD model mice (J20 strain) aging from 2 to 9 months by immunostaining. At 2 months, Aβ was only intraneuronal, whereas vessels were positive from 3 months in J20 mice. Compared to wild-type (WT), vessel density was increased at 2 months but decreased at 9 months in J20 mice, claudin-5 levels were decreased, and vascular endothelial growth factor (VEGF) levels were increased in the cortex and hippocampus of J20 mice brain at all time points. Albumin extravasation was evident from 3 months in J20 brains. Collagen 4 was increased at 2 and 3 months. Aquaporin 4 was spread beyond the vessels starting from 3 months in J20, which was restricted around the vessel in wild-type mice. In conclusion, the study showed that an early decrease in claudin-5 was associated with VEGF expression, indicating dysfunction of the blood–brain barrier. Decreased claudin-5 might cause the leakage of blood constituents into the parenchyma that alters astrocyte polarity and its functions.https://www.mdpi.com/2227-9059/11/1/50Alzheimer’s disease (AD)APP transgenic mouseamyloid βvessel leakageblood brain barrier (BBB) |
| spellingShingle | Abu Zaffar Shibly Abdullah Md. Sheikh Makoto Michikawa Shatera Tabassum Abul Kalam Azad Xiaojing Zhou Yuchi Zhang Shozo Yano Atsushi Nagai Analysis of Cerebral Small Vessel Changes in AD Model Mice Biomedicines Alzheimer’s disease (AD) APP transgenic mouse amyloid β vessel leakage blood brain barrier (BBB) |
| title | Analysis of Cerebral Small Vessel Changes in AD Model Mice |
| title_full | Analysis of Cerebral Small Vessel Changes in AD Model Mice |
| title_fullStr | Analysis of Cerebral Small Vessel Changes in AD Model Mice |
| title_full_unstemmed | Analysis of Cerebral Small Vessel Changes in AD Model Mice |
| title_short | Analysis of Cerebral Small Vessel Changes in AD Model Mice |
| title_sort | analysis of cerebral small vessel changes in ad model mice |
| topic | Alzheimer’s disease (AD) APP transgenic mouse amyloid β vessel leakage blood brain barrier (BBB) |
| url | https://www.mdpi.com/2227-9059/11/1/50 |
| work_keys_str_mv | AT abuzaffarshibly analysisofcerebralsmallvesselchangesinadmodelmice AT abdullahmdsheikh analysisofcerebralsmallvesselchangesinadmodelmice AT makotomichikawa analysisofcerebralsmallvesselchangesinadmodelmice AT shateratabassum analysisofcerebralsmallvesselchangesinadmodelmice AT abulkalamazad analysisofcerebralsmallvesselchangesinadmodelmice AT xiaojingzhou analysisofcerebralsmallvesselchangesinadmodelmice AT yuchizhang analysisofcerebralsmallvesselchangesinadmodelmice AT shozoyano analysisofcerebralsmallvesselchangesinadmodelmice AT atsushinagai analysisofcerebralsmallvesselchangesinadmodelmice |