Connexin expression in Huntington's diseased human brain.
In Huntington's diseased human brain, it is in the caudate nucleus (CN) and globus pallidus (GP) of the basal ganglia where nerve cell death is seen most dramatically. The distribution of five gap junction proteins (connexins 26, 32, 40, 43 and 50) has been examined in these areas in normal and Huntington's diseased human brain using immunohistochemical techniques. There was no Cx50 expression observed and Cx40 was localized in the endothelial cells of blood vessels, with the Huntington's diseased brains having more numerous and smaller blood vessels than normal tissue. Cx26 and Cx32 revealed a similar distribution pattern to each other in both normal and diseased brains with little labelling in the CN but clear labelling in the GP. Cx43, expressed by astrocytes, was the most abundant connexin type of those studied. In both normal and diseased brains Cx43 in the GP was homogeneously distributed in the neuropil. In the CN, however, Cx43 density was both increased with Huntington's disease and became located in patches. Glial fibrillary acidic protein(GFAP) staining of astrocytes was also highly increased in the CN compared with normal brains. These labelling patterns indicate a reactive astrocytosis around degenerating neurons with an increased expression of astrocytic gap junctions. The enhanced coupling state between astrocytes, assuming the junctions are functional, could provide an increased spatial buffering capacity by the astrocytes in an attempt to maintain a proper environment for the neurons, helping promote neuronal survival in this neurodegenerative disorder.
Vis
J C
JC
Department of Neurology, University Hospital Nijmegen, Nijmegen, The Netherlands.
Nicholson
L F
LF
Faull
R L
RL
Evans
W H
WH
Severs
N J
NJ
Green
C R
CR
D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002421:Caudate Nucleus / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D000072259:Connexin 26; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D017629:Gap Junctions / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005917:Globus Pallidus / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D000097002:Gap Junction beta-1 Protein; D000097003:Gap Junction alpha-5 Protein; D000099264:Connexin 50
D000072259:Connexin 26; D018031:Connexin 43; D017630:Connexins; D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein; D000097002:Gap Junction beta-1 Protein; D000097003:Gap Junction alpha-5 Protein; D000099264:Connexin 50; C000607042:GJB2 protein, human; C000607044:Gjb2 protein, rat