6-Hydroxydopamine increases the level of TNFα and bax mRNA in the striatum and induces apoptosis of dopaminergic neurons in hemiparkinsonian rats
2004
Аутори:
Mladenović, AleksandraPerović, Milka
Zogović, Nevena
Kanazir, Selma
Rakić, Ljubisav
Ruždijić, Sabera
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2003 by Elsevier B.V.
Метаподаци
Приказ свих података о документуАпстракт:
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 (TNFα) and its “death receptor” TNFαRI 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 TNFα 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 TNFαRI 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.
Кључне речи:
Parkinson’s disease; 6-OHDA; tumor necrosis factor alpha (TNFα)Извор:
Brain Research, 2004, 996, 2, 237-245
DOI: 10.1016/j.brainres.2003.10.035
ISSN: 0006-8993
PubMed: 14697501