title: 6-Hydroxydopamine increases the level of TNFalpha and bax mRNA in the striatum and induces apoptosis of dopaminergic neurons in hemiparkinsonian rats.
abstract: 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.
authors.affiliation: Laboratory of Molecular Neurobiology, Department of Neurobiology and Immunology, Institute for Biological Research, 29 Novembra 142, 11060 Belgrade, Serbia and Montenegro, Yugoslavia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Mladenović
authors.forename: Milka
authors.initials: M
authors.lastname: Perović
authors.forename: Nevena
authors.initials: N
authors.lastname: Raicević
authors.forename: Selma
authors.initials: S
authors.lastname: Kanazir
authors.forename: Ljubisav
authors.initials: L
authors.lastname: Rakić
authors.forename: Sabera
authors.initials: S
authors.lastname: Ruzdijić
mesh_terms: 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
chemical_list: 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