Use of tissue culture models to study neuronal regulatory trophic and toxic factors in the aged brain

Dementia is believed to result from the loss of selective neurons within the brain, but approaches for systematic study of that degenerative process are hampered by the complexity of the neuronal milieu. Tissue culture models provide a means to reduce dramatically the variables inherent in the study of neuronal plasticity. Three levels of complexity can be described: cellular and molecular diversity; primary and secondary interconnections; and finally, the dynamics influenced by age. The following review discusses the advantages and disadvantages of tissue culture models for the detailed study of neuronal trophic and toxic factors. Our selection of factors is broadened to include ions, intermediate metabolites, antioxidants, steroids, neuropeptides, gangliosides, metals, neurotransmitters, brain extracts, and protein molecules. Most of these factors have been shown to be altered in the aged brain, to have a significant effect on cultured neurons, or both. This multilevel analysis provides the reader with an overview of the events regulating neuronal survival, differentiation and death. An understanding of these basic questions is necessary to sequence the molecular events resulting in neuronal death.