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Androgens induce mitochondrial dysfunction and apoptosis in dopamine neurons
Author(s) -
Cunningham Rebecca Lynn,
Centonze Victoria E.,
Lechleiter James,
Giuffrida Andrea,
Roberts James L.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.618.14
Subject(s) - dopamine , dopaminergic , apoptosis , mitochondrion , neuroprotection , endocrinology , medicine , androgen , oxidative stress , microbiology and biotechnology , parkinson's disease , biology , chemistry , programmed cell death , hormone , disease , biochemistry
Parkinson's disease (PD) is a neurodegenerative condition associated with oxidative stress and dopamine neuronal loss in the nigrostriatal pathway. Aged men have a greater incidence of PD than women. While estrogens have been shown to play a neuroprotective role in PD, there is little information on androgens' actions on dopamine neurons. In this study, we examined the effects of androgens on mitochondria function and its downstream signaling pathways in a dopaminergic cell line (N27 cells). Our results show that physiological levels of testosterone (100 nM) caused mitochondrial dysfunction and apoptosis, as evidenced by increased free radical formation, decreased mitochondria membrane potential, and decreased levels of reduced thiols ‐ an indicator of reactive oxygenated species (ROS) generation. We also found that androgens activate the apoptotic PKCδ pathway via a caspase‐3 dependent mechanism. To determine the specificity of androgen‐induced apoptosis, we used the same experimental protocol on the non‐dopaminergic GnRH cell line. Androgens did not induce apoptosis in these neurons, suggesting that androgen‐induced apoptosis is not a generalized phenomenon and that it may be specific to dopamine neurons. These results show that androgenic influences may underlie the gender bias in Parkinson's disease. NIH grants F32NS061417‐01 to RLC.