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Platelets are responsible for the accumulation of ?-amyloid in blood clots inside and around blood vessels in mouse brain after thrombosis.

ABSTRACT: Platelets contain beta-amyloid precursor protein (APP) as well as A? peptide (A?) that can be released upon activation. During thrombosis, platelets are concentrated in clots and activated.We used in vivo fluorescent analysis and electron microscopy in mice to determine to what degree platelets are concentrated in clots. We used immunostaining to visualize A? after photothrombosis in mouse brains.Both in vivo results and electron microscopy revealed that platelets were 300-500 times more concentrated in clots than in non-clotted blood. After thrombosis in control mice, but not in thrombocytopenic animals, A? immunofluorescence was present inside blood vessels in the visual cortex and around capillaries in the entorhinal cortex.The increased concentration of platelets allows enhanced release of A? during thrombosis, suggesting an additional source of A? in the brains of Alzheimer's patients that may arise if frequent micro-thrombosis events occur in their brains.

SUBMITTER: Kucheryavykh LY

PROVIDER: S-EPMC5205543 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Platelets are responsible for the accumulation of β-amyloid in blood clots inside and around blood vessels in mouse brain after thrombosis.

Kucheryavykh Lilia Y LY Dávila-Rodríguez Josué J Rivera-Aponte David E DE Zueva Lidia V LV Washington A Valance AV Sanabria Priscilla P Inyushin Mikhail Y MY

Brain research bulletin 20161128

<h4>Introduction</h4>Platelets contain beta-amyloid precursor protein (APP) as well as Aβ peptide (Aβ) that can be released upon activation. During thrombosis, platelets are concentrated in clots and activated.<h4>Methods</h4>We used in vivo fluorescent analysis and electron microscopy in mice to determine to what degree platelets are concentrated in clots. We used immunostaining to visualize Aβ after photothrombosis in mouse brains.<h4>Results</h4>Both in vivo results and electron microscopy re ...[more]

PMID: 27908798

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Project description:Aquaporin-4 (AQP4) is located mainly in the astrocytic end-feet around cerebral blood vessels and regulates ion and water homeostasis in the brain. While deletion of AQP4 is shown to reduce amyloid-β (Aβ) clearance and exacerbate Aβ peptide accumulation in plaques and vessels of Alzheimer's disease mouse models, the mechanism and clearing pathways involved are debated. Here, we investigated how inhibiting the function of AQP4 in healthy male C57BL/6 J mice impacts clearance of Aβ40, the more soluble Aβ isoform. Using two-photon in vivo imaging and visualizing vessels with Sulfurodamine 101 (SR101), we first showed that Aβ40 injected as a ≤ 0.5-μl volume in the cerebral cortex diffused rapidly in parenchyma and accumulated around blood vessels. In animals treated with the AQP4 inhibitor TGN-020, the perivascular Aβ40 accumulation was significantly (P < 0.001) intensified by involving four times more vessels, thus suggesting a generalized clearance defect associated with vessels. Increasing the injecting volume to ≥ 0.5 ≤ 1 μl decreased the difference of Aβ40-positive vessels observed in non-treated and AQP4 inhibitor-treated animals, although the difference was still significant (P = 0.001), suggesting that larger injection volumes could overwhelm intramural vascular clearance mechanisms. While both small and large vessels accumulated Aβ40, for the ≤ 0.5-μl volume group, the average diameter of the Aβ40-positive vessels tended to be larger in control animals compared with TGN-020-treated animals, although the difference was non-significant (P = 0.066). Using histopathology and ultrastructural microscopy, no vascular structural change was observed after a single massive dose of TGN-020. These data suggest that AQP4 deficiency is directly involved in impaired Aβ brain clearance via the peri-/para-vascular routes, and AQP4-mediated vascular clearance might counteract blood-brain barrier abnormalities and age-related vascular amyloidopathy.

Dataset Information

Platelets are responsible for the accumulation of ?-amyloid in blood clots inside and around blood vessels in mouse brain after thrombosis.

Publications

Platelets are responsible for the accumulation of β-amyloid in blood clots inside and around blood vessels in mouse brain after thrombosis.

Similar Datasets

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