A potential defense mechanism against amyloid deposition in cerebellum
Autor: | Satoru Funamoto, Alam Shahnur, Hina Uchiyama, Tomohiro Miyasaka, Masaki Nakano, Masaki Nishimura, Yuuna Shirai, Takaomi C. Saido, Mohammad Moniruzzaman, Takashi Saito, Nobuto Kakuda, Seiko Ishihara |
---|---|
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Cerebellum Biophysics Mice Transgenic environment and public health Biochemistry Pathogenesis 03 medical and health sciences 0302 clinical medicine Interstitial fluid hemic and lymphatic diseases Internal medicine medicine Animals Humans Senile plaques Molecular Biology Potential mechanism Cerebral Cortex Amyloid beta-Peptides Chemistry Rhodamines fungi Extracellular Fluid Cell Biology Mice Inbred C57BL enzymes and coenzymes (carbohydrates) 030104 developmental biology Endocrinology medicine.anatomical_structure Amyloid deposition Lymphatic system Cerebral cortex 030220 oncology & carcinogenesis Cervical Vertebrae Lymph Nodes Sulfonic Acids hormones hormone substitutes and hormone antagonists |
Zdroj: | Biochemical and biophysical research communications. 535 |
ISSN: | 1090-2104 |
Popis: | Amyloid-β (Aβ) is the major component of senile plaques in Alzheimer’s disease (AD) brains. Senile plaques are generally observed in cerebral cortex (CTX) rather than cerebellum (CBL) in AD patients. However, it is not clear why CBL has less Aβ deposition than CTX. It is very important to elucidate the mechanism of suppressing Aβ deposition in CBL, because it contributes to understanding of not only AD pathogenesis but also prevention and cure of AD. In this study, we explored to figure out the potential mechanism of reducing Aβ deposition in CBL. We observed higher age-dependent elevation of Aβ level in CTX rather than CBL of human APP knock-in AD model mice, although we detected no significant differences in the levels of interstitial fluid Aβ in these brain tissues. These data imply that less Aβ deposition in CBL is due to enhanced Aβ clearance rather than altered Aβ production in CBL. To gain insights into Aβ clearance in CBL, we injected fluorescence-labeled Aβ in brain tissues. Importantly diffusion area of fluorescent Aβ in CBL was roughly six-times larger than that in CTX within 2 h of injection. In addition, injected Aβ area in CBL decreased sharply after 24 h and CBL-injected Aβ was robustly detected in deep cervical lymph nodes (DcLNs). In contrast, diffusion area of fluorescent Aβ in CTX was consistent up to 72 h and CTX-injected Aβ was faintly detected in DcLNs. Our data suggest that enhanced Aβ drainage in association with meningeal lymphatic system is responsible for less Aβ deposition in CBL. |
Databáze: | OpenAIRE |
Externí odkaz: |