Alpha-Smooth Muscle Actin mRNA and Protein Are Increased in Isolated Brain Vessel Extracts of Alzheimer Mice

Abstract

Alzheimer's disease (AD) is a severe neurodegenerative disorder of the brain, characterized by extracellular beta-amyloid (Aβ) plaques, intracellular tau pathology, neurodegeneration and inflammation. There is clear evidence that the blood-brain barrier is damaged in AD and that vessel function is impaired. Alpha-smooth muscle actin (αSMA) is a prominent protein expressed on brain vessels, especially in cells located closer to the arteriole end of the capillaries, which possibly influences the blood vessel contraction. The aim of the present study was to observe αSMA protein and mRNA expression in isolated brain vessel extracts and cortex in an Alzheimer mouse model with strong Aβ plaque deposition. Our data revealed a prominent expression of αSMA protein in isolated brain vessel extracts of AD mice by Western blot analysis. Immunostaining showed that these vessels were associated with Aβ plaques. Quantitative real-time PCR analysis confirmed this increase at the mRNA expression level and showed a significant increase of transforming growth factor beta-1 mRNA expression in AD mice. In situ hybridization demonstrated a strong expression pattern of αSMA mRNA in the whole cortex and hippocampus. In conclusion, our data provide evidence that αSMA protein and mRNA are enhanced in vessels in an AD mouse model, possibly counteracting vessel malfunction in AD.

The Interplay Between Beta-Amyloid 1–42 (Aβ1–42)-Induced Hippocampal Inflammatory Response, p-tau, Vascular Pathology, and Their Synergistic Contributions to Neuronal Death and Behavioral Deficits

“…A lower degree of α-SMA immunostaining was found in the blood vessels of AD patients compared to controls (Ervin et al, 2004) but also increased expression of α-SMA in preclinical AD cases (Ervin et al, 2004). Consistent with our results, another AD mouse model was found to express high α-SMA immunostaining near Aβ plaques in the blood vessels in the cortex (Hutter- Schmid and Humpel, 2016). In preliminary studies, we have also detected an increase in α-SMA immunostaining in the middle temporal cortex of AD cases using tissue microarray methods (Austria et al, unpublished).…”

“…For instance, endothelial cell adhesion molecules PECAM-1 and ICAM-1 (also known as CD31 and CD54, respectively) play a role in regulating interactions between leukocytes and the endothelium and are involved in the AD pathology through their contribution to the inflammatory process within blood vessels (Wennström and Nielsen, 2012). In the same way, the up-regulation of α-SMA, which plays a role in the contraction of the vessels, might be a compensatory mechanism in late-stage of the AD pathology in response to early vascular disruption in the BBB (Hutter- Schmid and Humpel, 2016).…”

Platelets isolated from an Alzheimer mouse damage healthy cortical vessels and cause inflammation in an organotypic ex vivo brain slice model

“…The release of MMPs was analyzed in isolated platelets and vessels from wildtype and transgenic mice. Vessels were isolated using a BSA centrifugation step as described in detail by us elsewhere 49 . Briefly, isolated platelets or vessels were resuspended in 100 µl Tyrode buffer and incubated for 60 min at 37 °C; then cells were centrifuged 1900 g 10 min and the supernatent analyzed by ELISA and the pellet measured for total protein using Bradford assay.…”

The Isolated Brain Microvessel: A Versatile Experimental Model of the Blood-Brain Barrier

“…The other mural cell, the microvascular smooth muscle cell, may also play a role in the development of vascular amyloid in AD. Microvessels were isolated from double transgenic Tg-SweDI AD mice and C57Bl/6 control mice, and smooth muscle α-actin (SMA) Western blotting showed a 2-fold elevation in αSMA in AD microvessels (Hutter-Schmid and Humpel, 2016).…”