Translocation of AIF in the human and rat striatum following protracted haloperidol, but not clozapine treatment

Apoptosis : an International Journal on Programmed Cell Death
K J SkoblenickR K Mishra

Abstract

Loss of mitochondrial membrane integrity and consequent release of apoptogenic factors may be involved in mediating striatal neurodegeneration after prolonged treatment with the typical antipsychotic drug haloperidol. Apoptosis-inducing factor (AIF), an intramitochondrial protein, may have a large influence on mediating haloperidol-induced striatal neuron destruction. Translocation of this protein from mitochondria to the nucleus promotes cell death independently of the caspase cascade. To examine how AIF may contribute to haloperidol-induced apoptosis, AIF translocation was observed in three haloperidol treatment paradigms. SH-SY5Y cells were treated with both haloperidol and clozapine and examined for AIF immunofluorescence. Immunohistochemistry was also performed on human striatal sections obtained from the Stanley Foundation Neuropathology Consortium and on rat brain sections following 28 days of antipsychotic drug treatment. In the cellular model haloperidol, but not clozapine treatment increased the nuclear AIF immunofluorescent signal and decreased cell viability. Corollary to these findings, striatal sections from patients who had taken haloperidol and rats who were administered haloperidol both had an elevated nuclear ...Continue Reading

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Citations

May 16, 2009·Journal of Neural Transmission·Santhrani Thaakur, G Himabindhu
Jan 19, 2012·Parkinson's Disease·Edward C LauterbachAntonio L Teixeira
Dec 31, 2011·Mammalian Genome : Official Journal of the International Mammalian Genome Society·James J CrowleyPatrick F Sullivan
Dec 5, 2015·Expert Opinion on Pharmacotherapy·Jean-Michel AzorinRaoul Belzeaux
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Jan 1, 2015·Biochimica Et Biophysica Acta·Sung-Yup ChoIn-Gyu Kim
May 22, 2021·Pharmacological Reviews·Samantha Christine SernoskieJack Paul Uetrecht

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