6-Hydroxydopamine increases the level of TNFalpha and bax mRNA in the striatum and induces apoptosis of dopaminergic neurons in hemiparkinsonian rats

• Published in: Brain research Vol. 996; no. 2; pp. 237 - 245
• Main Authors: Mladenović, Aleksandra, Perović, Milka, Raicević, Nevena, Kanazir, Selma, Rakić, Ljubisav, Ruzdijić, Sabera
• Format: Journal Article
• Language: English
• Published: Netherlands 23.01.2004
• Subjects: Adrenergic Agents - pharmacology; Animals; Apoptosis - physiology; bcl-2-Associated X Protein; Corpus Striatum - drug effects; Corpus Striatum - pathology; Dopamine - metabolism; Functional Laterality; Immunohistochemistry; In Situ Nick-End Labeling; Male; Nerve Degeneration - metabolism; Nerve Degeneration - pathology; Neurons - drug effects; Neurons - pathology; Neurons - physiology; Oxidopamine - pharmacology; Parkinsonian Disorders - pathology; Proto-Oncogene Proteins - drug effects; Proto-Oncogene Proteins c-bcl-2; Rats; Receptors, Tumor Necrosis Factor - drug effects; Receptors, Tumor Necrosis Factor - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; RNA, Messenger - drug effects; Time Factors; Tumor Necrosis Factor-alpha - drug effects; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0006-8993

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.