Poly (ADP-ribose) polymerase-1 initiated neuronal cell death pathway-do androgens matter?

K. Vagnerova, K. Liu, A. Ardeshiri, J. Cheng, S. J. Murphy, P. D. Hurn, P. S. Herson

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Activation of poly (ADP-ribose) polymerases (PARP) contributes to ischemic damage by causing neuronal nicotinamide adenine dinucleotide (NAD+) depletion, release of apoptosis-inducing factor and consequent caspase-independent cell death. PARP-mediated cell death is sexually dimorphic, participating in ischemic damage in the male brain, but not the female brain. We tested the hypothesis that androgen signaling is required for this male-specific neuronal cell death pathway. We observed smaller damage following focal cerebral ischemia (MCAO) in male PARP-1 knockout mice compared to wild type (WT) as well as decreased damage in male mice treated with the PARP inhibitor PJ34. Protection from ischemic damage provided by PJ-34 in WT mice is lost after removal of testicular androgens (CAST) and rescued by androgen replacement. CAST PARP-1 KO mice exhibit increased damage compared to intact male KO mice, an effect reversed by androgen replacement in an androgen receptor-dependent manner. Lastly, we observed that ischemia causes an increase in PARP-1 expression that is diminished in the absence of testicular androgens. Our data indicate that PARP-mediated neuronal cell death in the male brain requires intact androgen-androgen receptor signaling.

Original languageEnglish (US)
Pages (from-to)476-481
Number of pages6
JournalNeuroscience
Volume166
Issue number2
DOIs
StatePublished - Mar 17 2010

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Vagnerova, K., Liu, K., Ardeshiri, A., Cheng, J., Murphy, S. J., Hurn, P. D., & Herson, P. S. (2010). Poly (ADP-ribose) polymerase-1 initiated neuronal cell death pathway-do androgens matter? Neuroscience, 166(2), 476-481. https://doi.org/10.1016/j.neuroscience.2009.12.041