Modulation of connexin 43 in rotenone-induced model of Parkinson's disease.
Gap junctional communication plays an important role in various models of brain pathology, but the changes of gap junctions in Parkinsonism are still not understood. In this study, we show that a major gap junctional protein, connexin43 (Cx43), in astrocytes is enhanced both in a rat Parkinson's disease (PD) model induced with rotenone, a widely used pesticide that inhibits mitochondrial complex I, and in vitro in cultured astrocytes stimulated with rotenone. Enhancement of Cx43 protein levels in rotenone-treated cultured astrocytes occurred in parallel with an increase in gap junctional intercellular communication, but was not accompanied with an increase in Cx43 mRNA levels. Furthermore, the rotenone-induced increase of Cx43 protein levels both in vitro and in vivo was associated with increased levels of phosphorylated Cx43, which is required for gap junctional intercellular communication. In our rat PD model, phosphorylated Cx43 was selectively enhanced in the basal ganglia regions, which contain DA neurons or their terminal areas. The increase of Cx43 levels was lower in the substantia nigra pars compacta and the striatum than in the substantia nigra pars reticulata and the globus pallidus. Our findings indicate that modulation of Cx43 protein, and consequently gap junctional cellular communication, in astrocytes may play an important role in PD pathology.
Kawasaki
A
A
Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. asamik@hiroshima-u.ac.jp
Hayashi
T
T
Nakachi
K
K
Trosko
J E
JE
Sugihara
K
K
Kotake
Y
Y
Ohta
S
S
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002450:Cell Communication; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012402:Rotenone; D015398:Signal Transduction
D018031:Connexin 43; D012333:RNA, Messenger; D012402:Rotenone