Alterations of second messenger systems in the rat brain after 6-hydroxydopamine lesions of the medial forebrain bundle.
We studied the sequential changes in second messenger systems in the striatum and substantia nigra (SN) after 6-hydroxydopamine lesions of the medial forebrain bundle in rats. The animals were unilaterally lesioned in the medial forebrain bundle and the brains were analyzed at 1, 2, 4 and 8 weeks postlesion. [3H]Phorbol-12, 13-dibutyrate (PDBu), [3H]forskolin and [3H]rolipram were used to label protein kinase C (PKC), adenylyl cyclase and calcium/calmodulin-independent cyclic-AMP phosphodiesterase, respectively. The degeneration of nigrostriatal pathway produced a significant increase in [3H]PDBu binding in the ventromedial part of the ipsilateral striatum from 2 to 8 weeks postlesion. In the contralateral side, [3H]PDBu binding showed a transient increase in the SN only 4 weeks after lesioning. [3H]Forskolin binding showed a significant increase in the ipsilateral and contralateral striatum from 2 to 4 weeks postlesion. In the ipsilateral SN, a significant increase in [3H]forskolin binding was observed at 4 weeks after lesioning. However, no significant change in [3H]forskolin binding was observed in the contralateral SN during postlesion. On the other hand, [(3)H]rolipram binding showed no conspicuous alteration in the brain during postlesion. These results demonstrate that rats made hemiparkinsonism by unilateral 6-hydroxydopamine injection have a significant increase in [3H]PDBu and [3H]forskolin binding in the striatum and/or SN, whereas no significant change in [3H]rolipram binding is observed in these areas during postlesion. Our findings also suggest that the increase in [3H]forskolin binding is more pronounced than that in [3H]PDBu binding in the brain after unilateral 6-hydroxydopamine injection. Thus, our studies may provide valuable information concerning degeneration of the nigrostriatal pathway such as Parkinson's disease.
Araki
T
T
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan. tsuaraki@mail.cc.tohoku.ac.jp
Tanji
H
H
Kato
H
H
Mizugaki
M
M
Itoyama
Y
Y
D000818:Animals; D000978:Antiparkinson Agents / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D002273:Carcinogens / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism / Q000502:physiology; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011760:Pyrrolidinones / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram; D015290:Second Messenger Systems / Q000187:drug effects*; D013378:Substantia Nigra / Q000378:metabolism / Q000502:physiology; D014316:Tritium
D000978:Antiparkinson Agents; D002273:Carcinogens; D011760:Pyrrolidinones; D014316:Tritium; D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; D016627:Oxidopamine; D020889:Rolipram