scholarly journals Topological analyses in APP/PS1 mice reveal that astrocytes do not migrate to amyloid-β plaques

2015 ◽  
Vol 112 (51) ◽  
pp. 15556-15561 ◽  
Author(s):  
Elena Galea ◽  
Will Morrison ◽  
Eloise Hudry ◽  
Michal Arbel-Ornath ◽  
Brian J. Bacskai ◽  
...  

Although the clustering of GFAP immunopositive astrocytes around amyloid-β plaques in Alzheimer’s disease has led to the widespread assumption that plaques attract astrocytes, recent studies suggest that astrocytes stay put in injury. Here we reexamine astrocyte migration to plaques, using quantitative spatial analysis and computer modeling to investigate the topology of astrocytes in 3D images obtained by two-photon microscopy of living APP/PS1 mice and WT littermates. In WT mice, cortical astrocyte topology fits a model in which a liquid of hard spheres exclude each other in a confined space. Plaques do not disturb this arrangement except at very large plaque loads, but, locally, cause subtle outward shifts of the astrocytes located in three tiers around plaques. These data suggest that astrocytes respond to plaque-induced neuropil injury primarily by changing phenotype, and hence function, rather than location.

2021 ◽  
Author(s):  
Mosi Li ◽  
Akihiro Kitamura ◽  
Joshua Beverley ◽  
Juraj Koudelka ◽  
Jessica Duncombe ◽  
...  

Large vessel disease and carotid stenosis are key mechanisms contributing to vascular cognitive impairment (VCI) and dementia. Our previous work, and that of others, using rodent models, demonstrated that bilateral common carotid stenosis (BCAS) leads to cognitive impairment via gradual deterioration of the glial-vascular unit and accumulation of amyloid-β (Aβ) protein. Since brain-wide drainage pathways (glymphatic) for waste clearance, including Aβ removal, have been implicated in the pathophysiology of VCI via glial mechanisms, we hypothesized that glymphatic function would be impaired in a BCAS model and exacerbated in the presence of Aβ. Male wild-type and Tg-SwDI (model of microvascular amyloid) mice were subjected to BCAS or sham surgery which led to a reduction in cerebral perfusion and impaired spatial learning and memory. After 3 months survival, glymphatic function was evaluated by cerebrospinal fluid (CSF) fluorescent tracer influx. We demonstrated that BCAS caused a marked regional reduction of CSF tracer influx in the dorsolateral cortex and CA1-DG molecular layer. In parallel to these changes increased reactive astrogliosis was observed post-BCAS. To further investigate the mechanisms that may lead to these changes, we measured the pulsation of cortical vessels using two-photon microscopy. BCAS impaired vascular pulsation in pial arteries in WT and Tg-SwDI mice. Since our findings show that BCAS may influence VCI by impaired glymphatic drainage and reduced vascular pulsation we propose that these additional targets need to be considered when treating VCI.


2012 ◽  
Vol 20 (4) ◽  
pp. 12-16
Author(s):  
Tilman Franke ◽  
Sebastian Rhode

Two-photon microscopy (2PM) provides three-dimensional (3D) and four-dimensional (4D) (x, y, z, t) imaging in living specimens or under experimental physiological conditions very close to live. In conjunction with fluorescent labels, 2PM provides a powerful means of investigating the relationships between structure and function at the microscopic level that are key to understanding biological systems. This technique is able to provide time-resolved, 3D images of dynamic systems with near-diffraction-limited resolution and highly specific structural contrast.


2016 ◽  
Vol 54 (12) ◽  
pp. 1343-1404
Author(s):  
A Ghallab ◽  
R Reif ◽  
R Hassan ◽  
AS Seddek ◽  
JG Hengstler

ACS Omega ◽  
2020 ◽  
Author(s):  
Kazushi Yamaguchi ◽  
Kohei Otomo ◽  
Yuichi Kozawa ◽  
Motosuke Tsutsumi ◽  
Tomoko Inose ◽  
...  

2021 ◽  
Vol 18 (2) ◽  
pp. 220-220
Author(s):  
Weijian Zong ◽  
Runlong Wu ◽  
Shiyuan Chen ◽  
Junjie Wu ◽  
Hanbin Wang ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vincent D. Ching-Roa ◽  
Eben M. Olson ◽  
Sherrif F. Ibrahim ◽  
Richard Torres ◽  
Michael G. Giacomelli

An amendment to this paper has been published and can be accessed via a link at the top of the paper.


2009 ◽  
Vol 34 (11) ◽  
pp. 1684 ◽  
Author(s):  
Nicolas Olivier ◽  
Alexandre Mermillod-Blondin ◽  
Craig B. Arnold ◽  
Emmanuel Beaurepaire

Biomedicines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 10
Author(s):  
Feby Wijaya Pratiwi ◽  
Chien-Chung Peng ◽  
Si-Han Wu ◽  
Chiung Wen Kuo ◽  
Chung-Yuan Mou ◽  
...  

Mesoporous silica nanoparticles (MSNs) have emerged as a prominent nanomedicine platform, especially for tumor-related nanocarrier systems. However, there is increasing concern about the ability of nanoparticles (NPs) to penetrate solid tumors, resulting in compromised antitumor efficacy. Because the physicochemical properties of NPs play a significant role in their penetration and accumulation in solid tumors, it is essential to systematically study their relationship in a model system. Here, we report a multihierarchical assessment of the accumulation and penetration of fluorescence-labeled MSNs with nine different physicochemical properties in tumor spheroids using two-photon microscopy. Our results indicated that individual physicochemical parameters separately could not define the MSNs’ ability to accumulate in a deeper tumor region; their features are entangled. We observed that the MSNs’ stability determined their success in reaching the hypoxia region. Moreover, the change in the MSNs’ penetration behavior postprotein crowning was associated with both the original properties of NPs and proteins on their surfaces.


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