Neuroprotective effects of testosterone in a naturally occurring model of neurodegeneration in the adult avian song control system.

Seasonal regression of the avian song control system, a series of discrete brain nuclei that regulate song learning and production, serves as a useful model for investigating the neuroprotective effects of steroids. In seasonally breeding male songbirds, the song control system regresses rapidly when males are transferred from breeding to nonbreeding physiological conditions. One nucleus in particular, the HVC, regresses in volume by 22% within days of castration and transfer to a nonbreeding photoperiod. This regression is mediated primarily by a 30% decrease in neuron number, a result of a caspase-dependent process of programmed cell death. Here we examine whether testosterone (T) can act locally in the brain to prevent seasonal-like neurodegeneration in HVC. We began to infuse T intracerebrally near HVC on one side of the brain in breeding-condition male white-crowned sparrows 2 days prior to T withdrawal and shifting them to short-day photoperiods. The birds were killed 3 or 7 days later. Local T infusion significantly protected ipsilateral HVC from volume regression and neuron loss. In addition, T infusion significantly reduced the number, density, and number/1,000 neurons of activated caspase-3 cells and cells positive for cleaved PARP, both markers for programmed cell death, in the ipsilateral HVC. T infusion near HVC also prevented regression of ipsilateral efferent targets of HVC neurons, including the volumes of robust nucleus of the arcopallium (RA) and Area X and the soma area and density of RA neurons. Thus T can act locally in the brain to have a neuroprotective effect and act transsynaptically to prevent regression of efferent nuclei.