STEROIDS AS TROPHIC FACTORS--AGING NEUROMUSCULAR SYSTEM

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Using a simple neuromuscular system, this proposal focuses on the influence of androgens in the maintenance of motoneuron number, morphology, and function in aging. This system consists of two sexually dimorphic nuclei in the rat spinal cord, the spinal nucleus of the bulbocavernosus (SNB) and the dorsolateral nucleus (DLN) and the muscles of the perineum they innervate. While present in males these nuclei and their target muscles are reduced or absent in females. Androgens serve a trophic function in the development and adult maintenance of this system, for example regulating neuron number and dendritic growth during development, and maintaining motoneuron morphology and synaptology in adulthood. The experiments proposed examine the effect of the declines in androgen levels that occur with advancing age on these steroid-sensitive motoneurons. Three different features of these motoneuron populations will be examined: motoneuron number, morphology, and function. Motoneuron number will be assessed at a series of time points corresponding to the natural changes in circulating androgen in both sexually dimorphic and nondimorphic steroid-sensitive populations, to determine whether declines in androgen are reflected in the loss of motoneurons. By maintaining androgen levels or accelerating their decline, the influence of androgens on motoneuron survival will be directly assessed. The normal time course of regressive changes and the causal relation with age-related declines in androgens will be tested. The retention of structural plasticity in motoneuron morphology will also be determined. Finally, functional aspects of steroid accumulation and excitability will be assessed with regard to changes with age and hormonal condition. Because neurons can not be replaced in mature mammalian nervous systems, understanding the factors which control the death of neurons in aging is critical for our understanding of the aging process and age-related declines in neurobehavioral function.