Immunogold study of altered expression of some interendothelial junctional molecules in the brain blood microvessels of diabetic scrapie-infected mice.
Quantitative immunogold procedure was used to study the distribution of molecular components of interendothelial junctions in blood-brain barrier (BBB) microvessels of scrapie infected SJL/J hyperglycemic mice showing obesity and reduced glucose tolerance. Samples of brain (fronto-parietal cerebral cortex and thalamo-hypothalamic region) obtained from hyperglycemic (diabetic) mice and from non- infected, normoglycemic (non-diabetic) SJL/J mice, were processed for immunocytochemical examination. The localization of the following tight junction (TJ)-associated proteins was studied: occludin as an integral membrane (transmembrane) protein, and zonula occludens one (ZO-1) as a peripheral protein. The localization of beta-catenin as a representative of the cadherin/catenin complex that is typical for adherens junctions (AJs) also was studied. Morphometric analysis revealed that the density of immunosignals for occludin, represented by colloidal gold particles (GPs), was significantly lower in the brain microvessels of diabetic than in non-diabetic mice. No significant differences in the density of immunosignals for ZO-1 and beta-catenin between both experimental mouse groups were observed. It indicates that abnormal glucose metabolism affects mostly occludin which is believed to play a fundamental role in the maintenance of the tightness of endothelial lining in brain microvascular network and thereby in the preservation of its barrier function. These results also support the previously expressed opinion that occludin, detected with the applied morphological method, can be considered a sensitive indicator of altered molecular architecture of the interendothelial junctions due to the action of some metabolic or pathological insults.
Vorbrodt
Andrzej W
AW
Laboratory of Cytochemistry, Department of Developmental Neurobiology, New York State Office of Mental Retardation and Developmental Disabilities, Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA. dobrogowska@msn.com
Dobrogowska
Danuta H
DH
Tarnawski
Michal
M
Meeker
Harry C
HC
Carp
Richard I
RI
D022005:Adherens Junctions / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D003920:Diabetes Mellitus / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006943:Hyperglycemia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D012608:Scrapie / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin / Q000378:metabolism
D015415:Biomarkers; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin