3.1.2 Reduced expression of TJ and adhesion proteins
Decreased expression of TJ and adhesion proteins in spinal cords from ALS patients has been confirmed using PCR and Western Blot. Henkelet al. assessed mRNA expression of zonula occludens-1, occludin, and claudin-5 in lumbar spinal cord homogenates from individuals with ALS (30 sporadic and 4 familial cases) and 16 non-ALS controls (Henkel, Beers, Wen, Bowser & Appel, 2009). A significant reduction in zonula occludens-1 and occludin levels were identified in sporadic ALS and familial ALS, respectively, while claudin-5 was unchanged in both sporadic and familial ALS. In another study, a significant decrease in most TJ and adhesions proteins were reported in ALS spinal cord (cervical and lumbar) relative to non-ALS controls, including zonula occludens-1, occludin, claudin-5, JAM-1 and VE-cadherin (Garbuzova-Davis et al., 2012). Despite decreased TJ protein expression at the ALS BSCB, the junction morphology was generally well-preserved as assessed by electron microscopy (Sasaki, 2015). Based on these TJ and adhesion junction reductions, it would be predicted that spinal cord access of molecules would be increased as a result of increased paracellular permeability.