Caspase-3 activation in rat frontal cortex following treatment with typical and atypical antipsychotics

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
L Fredrik JarskogJeffrey A Lieberman

Abstract

In schizophrenia, studies indicate that apoptotic susceptibility in cortex may be increased. A role for apoptosis in schizophrenia could potentially contribute to post-mortem evidence of reduced cortical neuropil and neuroimaging studies showing progressive cortical gray matter loss. Interestingly, antipsychotic treatment has been associated with higher cortical levels of anti-apoptotic Bcl-2 protein in rat cortex and preliminary data has suggested a similar association in schizophrenia and bipolar disorder. To better understand the effects of antipsychotics on apoptotic regulation, rats were administered haloperidol, clozapine, quetiapine, or saline daily for 4 weeks. Multiple apoptotic markers, including Bcl-2, pro-apoptotic Bax, anti-apoptotic XIAP, and the downstream protease caspase-3 were measured in frontal cortex using Western blot. Caspase-3 activity, activated caspase-3-positive cell number, and DNA/histone fragmentation levels were also determined. Western blot showed that immunoreactivity of Bax and Bcl-2 bands were unchanged with treatment. However, mean density of the 19 kD activated caspase-3 band was 55% higher with haloperidol (p<0.001), 40% higher with clozapine (p<0.05), and 48% higher with quetiapine (p<0.01...Continue Reading

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Citations

Sep 7, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Anilkumar PillaiSahebarao P Mahadik
Dec 5, 2015·Expert Opinion on Pharmacotherapy·Jean-Michel AzorinRaoul Belzeaux
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Feb 11, 2020·Frontiers in Psychiatry·Jing QiShao-Qing Ju
May 22, 2021·Pharmacological Reviews·Samantha Christine SernoskieJack Paul Uetrecht

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