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The Journal of Neuroscience, April 20, 2005, 25(16):4004-4013; doi:10.1523/JNEUROSCI.5279-04.2005

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Development/Plasticity/Repair
Gonadal Steroid Attenuation of Developing Hamster Facial Motoneuron Loss by Axotomy: Equal Efficacy of Testosterone, Dihydrotestosterone, and 17- Estradiol

Christopher B. Huppenbauer,^1,2 Lisa Tanzer,¹ Lydia L. DonCarlos,¹ and Kathryn J. Jones^1,2

¹Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois 60153, and ²Research and Development Service, Hines Veterans Affairs Hospital, Hines, Illinois 60141

In the hamster facial nerve injury paradigm, we have established that androgens enhance both functional recovery from facial nerve paralysis and the rate of regeneration in the adult, through intrinsic effects on the nerve cell body response to injury and via an androgen receptor (AR)-mediated mechanism. Whether these therapeutic effects of gonadal steroids encompass neuroprotection from axotomy-induced cell death is the focus of the present study. Virtually 100% of adult hamster facial motoneurons (FMNs) survive axotomy at the stylomastoid foramen (SMF), whereas, before postnatal day 15 (P15), developing FMNs undergo substantial axotomy-induced cell death. The first part of the present study focuses on determining when ARs are first expressed in developing hamster FMNs. Using AR immunocytochemistry, it was found that males express ARs by P2 and females by P4, which is the earliest demonstration of AR expression in mammalian motoneurons reported thus far in the literature. The second half examines the neuroprotective effects of testosterone propionate, 17- estradiol, and dihydrotestosterone on FMNs of P7 hamsters after facial nerve transection at the SMF. The results demonstrate that androgens and estrogens are equally able to rescue 20% of FMNs from axotomy-induced cell death, with the effects permanent. This study is the first to investigate the effects of both androgens and estrogens on axotomy-induced cell death in one system and, with our previously published work, to validate the hamster FMN injury paradigm as a model of choice in the investigation of both neurotherapeutic and neuroprotective actions of gonadal steroids.

Key words: androgen receptor; testosterone; estrogen; dihydrotestosterone; motoneuron; development; peripheral nerve injury

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Received Dec 27, 2004; revised March 5, 2005; accepted March 9, 2005.

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