Angiotensin II protects cultured midbrain dopaminergic neurons against rotenone-induced cell death

Tom N. Grammatopoulos, Ferogh Ahmadi, Susan M. Jones, Marc W. Fariss, James A. Weyhenmeyer, W. Michael Zawada

Research output: Contribution to journalArticlepeer-review


In this study, we demonstrate that angiotensin II (Ang II) protects dopamine (DA) neurons from rotenone toxicity in vitro. Primary ventral mesencephalic (VM) cultures from E15 rats were grown for 5 days and then cultured in the presence of the mitochondrial complex I inhibitor, rotenone. Acute exposure (20 h) to 20 nM rotenone reduced the number of tyrosine hydroxylase-positive (TH+) neurons by 50 ± 6% when compared to untreated cultures. Pre-treatment of VM cultures with 100 nM Ang II decreased TH+ neuronal loss to 25 ± 10% at the 20-nM rotenone concentration. Ang II in the presence of the angiotensin type 1 receptor (AT1R) antagonist, losartan, was even more effective in protecting DA neurons showing a loss of only 13 ± 4% at 20 nM rotenone. Conversely, the AT2R antagonist, PD123319, abolished the protective effects of Ang II. Furthermore, both the NMDA receptor antagonist, MK801, and the antioxidant, alpha-tocopheryl succinate (vitamin E analogue), prevented rotenone-induced toxicity. Here, we show that acute exposure of VM cultures to the pesticide rotenone leads to dopaminergic neuronal cell death and that angiotensin acting through the AT2 receptor protects dopamine neurons from rotenone toxicity.

Original languageEnglish (US)
Pages (from-to)64-71
Number of pages8
JournalBrain Research
Issue number1-2
StatePublished - May 31 2005


  • Alpha-tocopheryl succinate
  • Angiotensin
  • AT receptor
  • Dopamine neurons
  • Losartan
  • MK801
  • Parkinson's disease
  • PD123319

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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