Glycogen synthase kinase 3β and its phosphorylated form (Y216) in the paraquat-induced model of parkinsonism.
Parkinson's disease is a slowly progressing disease, due to a lesion of dopaminergic neurons in the substantia nigra and a dramatic loss of dopamine in the striatum. It is now accepted that several environmental agents including the herbicide paraquat (PQ) may contribute to its pathogenesis. However, till now nothing is known about the role of glycogen synthase kinase-3β (GSK-3β) in the PQ toxicity. Therefore, the aim of this study was to examine the influence of 37-week administration of PQ in rats on the immunohistochemically measured levels of the total GSK-3β and its active, tyrosine 216 (pY216)-phosphorylated form in subcellular fractions of the midbrain with pons, as well as of the striatum. The present results revealed that the long-term PQ administration increased the levels of total and active forms of GSK-3β in the midbrain with pons, whereas decreased them in the striatum. Examination of the lesion extent showed a decrease in the number of tyrosine-immunoreactive neurons in the substantia nigra pars compacta, ventral tegmental area, and locus coeruleus, as well as lower DOPAC/dopamine ratio and noradrenaline level in the striatum in rats treated with PQ. The long-term PQ administration disturbed also motor activity of rats. Summarizing, the present data indicate that the long-term exposure of rats to PQ, a commonly used herbicide, diversely alters levels of GSK-3β in different brain structures, which may be associated with their vulnerability to its toxicity.
Department of Cellular Signaling, Medical Research Center, Polish Academy of Sciences, 5 Pawińskiego St., 02-106 Warsaw, Poland.
Martyna
M
Songin
Joanna B
JB
Strosznajder
Magdalena
M
Fitał
Katarzyna
K
Kuter
Wacław
W
Kolasiewicz
Przemysław
P
Nowak
Krystyna
K
Ossowska
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000201:enzymology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010269:Paraquat / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology; D014443:Tyrosine / Q000378:metabolism
D014443:Tyrosine; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D010269:Paraquat