COV TSWV YIM: kev sim ua ntej pom tias dopamine muaj feem xyuam rau DeltaFosb qib.
Eur J Neurosci. 1996 Feb; 8 (2): 365-81.
Doucet JP, Nakabeppu Y, Bedard PJ, Kev Cia Siab BT, Nestler EJ, Jasmin BJ, Chen JS, Iadarola MJ, St-Jean M, Wigle N, Blanchet P, Grondin R, Robertson GS.
Tau qhov twg los
Department of Pharmacology, Tsev Kawm Ntawv ntawm Ottawa, Ottawa, Ontario, Canada K1H 8M5.
Abstract
Siv cov tshuaj tiv thaiv uas paub txog cov khoom lag luam ntawm txhua tus tswvcuab hauv fos tsev neeg ntawm cov caj ces thaum ntxov, nws tau pom tias kev rhuav tshem ntawm nigrostriatal txoj kev los ntawm 6-hydroxydopamine (6-OHDA) cov qhov txhab ntawm cov kab mob medial forebrain bundle ua kom ntev (> 3 hli) qhov siab ntawm Fos-zoo li immunoreactivity hauv striatum. Siv cov txheej txheem rov ua haujlwm retrograde, peb tau pom yav dhau los tias qhov kev nce hauv Fos zoo li kev tiv thaiv kab mob yog nyob rau feem ntau ntawm striatal neurons uas ua rau lub globus pallidus. Hauv txoj kev tshawb nrhiav tam sim no, Western blots tau ua rau nuclear kev rho tawm los ntawm qhov tseem ceeb thiab thim rov qab ntawm 6-OHDA-lesioned nas los txiav txim siab qhov tseeb ntawm Fos-immunoreactive protein (s) lub luag haujlwm rau qhov nce no. Kwv yees li ntawm 6 lub lis piam tom qab mob 6-OHDA, qhia ntawm ob qho Fos-ntsig txog antigens nrog cov pom tias cov npliag molecular ntawm 43 thiab 45 kDa tau txhim kho nyob rau hauv cov tawv ntoo uas tsis ua haujlwm. Chropopopididol cov thawj coj kuj tseem xaiv cov lus hais txhawb ntxiv ntawm cov Fos ntsig txog antigens, tawm tswv yim tias lawv induction tom qab dopaminergic kev txwv yog kho kom haum xeeb los ntawm kev txo qis ntawm D2-zoo li dopamine receptors.
Western blot immunostaining siv antibody uas pom tau tias N-Termus ntawm FosB tau qhia tias 43 thiab 45 kDa Fos-ntsig txog antigens vim yog dopaminergic kev tiv thaiv thiab cov kev kho mob haloperidol yuav muaj feem xyuam rau ib daim FosB hu ua deltaFosB. Zoo ib yam li cov lus pom zoo no, retrograde tracing experiments paub tseeb tias deltaFosB-zoo li immunoreactivity nyob rau hauv cov pob txha deafferented yog nyob hauv feem ntau hauv cov paj hlwb.
Gel hloov cov kev sim tau pom tias qhov AP-1 los ua qhov kev sib tw hauv cov kabmob uas muaj tus kabmob xws li FosB (xws li cov protein), qhia tias qhov enhanced deltaFosB qib yuav kho cov teebmeem ntawm cov dopamine ntev heev ntawm AP-1-regulated noob hauv striatopallidal neurons. Hauv kev sib piv, muaj kev tswj hwm ntawm D1 zoo li receptor agonist CY 208243 rau 6-OHDA-lesioned nas tsuag dramatically enhanced deltaFosB zoo li immunoreactivity hauv striatal neurons projecting rau tus nqi ntau heev. Western blot immunosing qhia tias deltaFosB thiab, kom tsawg zog, FosB yog siab ntawm D1 zoo li kev tswj hwm txoj kev loj hlob. Ob qhov kev txav transcriptase-polymerase cov tshuaj tiv thaiv thiab cov ribonuclease kev tiv thaiv kev soj ntsuam tau qhia tias cov kev ntsuas deltafosB mRNA tau zoo heev hauv qhov kev ntseeg ntawm kev ntseeg ntawm D1 zoo li agonist kev tswj xyuas.
Thaum kawg, peb tau soj ntsuam qhov tshwm sim ntawm kev tswj hwm ntev ntawm D1-zoo li thiab D2 zoo li dopamine receptor agonists ntawm striatal deltaFosB kev hais tawm hauv 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate qauv ntawm Parkinson tus kab mob Cov. Hauv cov tsiaj liab ua rau Parkinsonian los ntawm MPTP, muaj qhov nce me hauv deltaFosB zoo li protein (s), thaum txoj kev loj hlob ntawm dyskinesia ua los ntawm D1-zoo li agonist kev tswj hwm tau nrog los ntawm kev nce ntau hauv DeltaFosB-zoo li protein (s). Hauv kev sib piv, kev tswj hwm ntawm kev ua haujlwm ntev li D2 zoo li agonist cabergoline, uas ua rau Parkinsonian cov tsos mob yam tsis muaj kev ua kom tsis muaj kabmob dyskinesia txo deltaFosB qib mus rau qhov qub. Ua ke, cov ntsiab lus tshwm sim qhia tau hais tias kev hloov kho hauv dopaminergic neurotransmission ua ib qho kev sib tw siab zoo li cov protein (delta) xws li cov kabmob thiab cov paj hlwb.
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