6-Hydroxydopamine increases the level of TNFalpha and bax mRNA in the striatum and induces apoptosis of dopaminergic neurons in hemiparkinsonian rats.
This study was focused on the apoptosis (programmed cell death) induction involved in the loss of dopaminergic (DA-ergic) neurons in 6-hydroxydopamine (6-OHDA) hemiparkinsonian rats. The apoptosis in the striatum and substantia nigra pars compacta (SNpc), was examined 6, 24 h and 7 days after the 6-OHDA lesions employing the TUNEL method. The changes in mRNA levels of pro-apoptotic protein tumor necrosis factor alpha (TNFalpha) and its "death receptor" TNFalphaRI and then bax mRNA, as an important regulator of apoptotic neurodegeneration were followed by RT-PCR procedure. In situ analysis revealed an increased number of TUNEL-positive neurons in 6-OHDA-treated animals in all examined time points. The highest number of apoptotic neurons was detected 24 h after the lesion, both in the ipsilateral striatum (3.41+/-0.18) and SNpc (5.8+/-0.79). A significant increase in the level of TNFalpha mRNA was observed in 6-OHDA-lesioned striatum, with maximal value after 24 h (46%) comparing to the control. In contrast, 6-OHDA did not significantly change the level of TNFalphaRI mRNA in any time point. Six and 24 h post-operatively, we observed a significant increase of bax mRNA expression (40% and 45%, respectively) in the ipsilateral striatum of treated animals in comparison with the right striatum of the controls. However, the highest level of the bax mRNA expression was reached 7 days after the surgery (94%) in the ipsilateral striatum of 6-OHDA-treated animals. These results suggest that striatal injection of 6-OHDA can induce early changes that would be an important regulator of apoptotic neurodegeneration of dopamine-producing neurons, during the first post-operative week.
Mladenović
Aleksandra
A
Laboratory of Molecular Neurobiology, Department of Neurobiology and Immunology, Institute for Biological Research, 29 Novembra 142, 11060 Belgrade, Serbia and Montenegro, Yugoslavia.
Perović
Milka
M
Raicević
Nevena
N
Kanazir
Selma
S
Rakić
Ljubisav
L
Ruzdijić
Sabera
S
D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D007839:Functional Laterality; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D018663:Adrenergic Agents; C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine