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Investigating the microvascular dysfunction in the Frontotemporal Dementia using a progranulin‐deficient mice model

Year: 2024
Type: article
Abstract: BACKGROUND: Despite being the second most common form of dementia, vascular contributions of Frontotemporal Dementia are understudied. Recent data from patients and preliminary experiments have indicated that in progranulin-deficient mice, an increased number of cortical capillaries are stalled, and cerebral blood flow is reduced. Here, we examined the underlying mechanism contributing to microvascular dysfunction in FTD. METHOD: Blood-brain barrier (BBB) integrity was examined using immunohistochemistry and protein analyses. We compared PGRN-deficient mice to controls and tested for the tight junction proteins Claudin-5, Occludin, and markers of BBB leakage, such as Albumin. High Resolution in vivo two-photon Imaging was utilized to detect the capillary stalls and capillary blood flow in the cortical capillaries, and the images were analyzed using MATLAB and ImageJ software. RESULT: We discovered that the number of blood vessels significantly decreased in the 10-11 month-old PGRN-deficient mice compared to controls. Furthermore, the tight junction protein levels of Claudin-5 and Occludin are significantly reduced in PGRN-deficient mice compared to age and sex-matched controls. Finally, in-vivo multiphoton experiments revealed a reduction in cerebral blood flow associated with a increased number of capillary stalling. CONCLUSION: This study shows that the BBB is damaged in PGRN-deficient mice, accompanied by microvascular dysfunction and hypoperfusion. The data suggest that PGRN-deficient mice could be an ideal model to investigate vascular contributions to FTD.
DOI: 10.1002/alz.093422
Authors: Supriya Chakraborty, Sofia Franciosa, Oliver Bracko
Institution: University of Miami
Language: English
Subfield: Neurology
Open Access status: hybrid
Estimated APC paid: $4,000
OpenAlex ID: W4406049733
FWCI: 0.136
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Cited by: 1
Related to: 10