Adam Anthony

Neurophysiology

Several recent studies have provided evidence supporting the hypothesis that a major mechanism of neuronal dysfunction during senescence is an inhibition or impairment in transcriptional-translational aspects of nucleic acid-protein metabolism. This hypothesis stems from observations that aging is associated with a progressive loss of brain protein and from recent cytochemical data indicating that neuronal RNA depletion is more severe in lesion-prone brain areas in individuals with Alzheimer's disease than in age-matched elderly subjects with no clinical symptoms of brain dysfunction. Thus, one basis for undertaking our research was the conviction that quantification of nucleic acid and protein-response patterns, as an adjunct to conventional histopathological and behavioral markers of brain dysfunction, would provide crucial insights into the mechanisms involved in the induction of such neuropathic changes as plaque formation, pigment deposition, and neurofibrillar tangles. Among the aims of our research are to (1) identify specific brain compartments in Alzheimer's patients, and in aged mice that are selectively prone to injury, using extent of neuronal RNA and protein depletion as an indicator of neuropathy, and (2) obtain correlative data on nucleic-acid response patterns in the brain, endocrine glands, and other body systems as a function of age.

Three main analytical approaches are (1) cytophotometric determinations of DNA, RNA, and proteins using scanning-integrating microspectrophotometry, and (2) conventional differential staining for cytomorphological and morphometric studies.