It has been suggested that immunologic processes are involved in the etiology of these senescence-related CNS changes which are responsible for impaired cognitive function in aged individuals. This hypothesis is based partly upon evidence that humoral brain-reactive antibodies (BRA) are a correlate of cognitive dysfunction in aged humans. The purpose of the proposed studies is to test this hypothesis more directly by determining the relationship between BRA and cognitive dysfunction in animal models. One experiment is proposed to compare life-span changes in behavioral abilities of several mouse strains exhibiting heterochronic, life-span increases in BRA. Age groups of 5 selected strains will be administered various tests for learning and memory abilities. Subsequently, serum BRA of the mice will be determined by indirect immunofluorescence and by serum + complement-induced 51-Cr release from neuroblastoma. Based upon the immune hypothesis, it is expected that deteriorations in performance on the learning or memory tests by the strains will be more related to the life-span time-course of their BRA increases than to chronological age. A second experiment is proposed to test further the hypothesized relationship, through examination of BRA and behavioral abilities of young mice following their receipt of hemopoietic cells from senescent mice. It is expected that BRA formation will occur in the young mice following cell transfers, and that the time-course of BRA formation will be paralleled by deteriorations in performance on the learning or memory tests. An overall expectation is that tests designed to measure qualitatively distinguishable learning and memory abilities should yield parallel findings with normally senescent mice and young mice found to have senescent-like levels of BRA. The relationship between BRA and deterioration of sensory, motor, and reflexive processes will also be examined in the various animal models, in order that the relationship between BRA and """"""""non-cognitive"""""""" behavioral markers of aging can be considered. The significance of these experiments is that they will indicate the potential for future studies to identify specific immunologic determinants of neurologic deterioration in aging. Should a clear relationship between BRA and cognitive dysfunction be obtained, several mouse strains will be available as models for identification of those determinants, and for the identification of therapeutic measures, chemical or nonchemical, for prevention or alleviation of senescence-related cognitive dysfunction.
| Retz, K C; Trimmer, C K; Forster, M J et al. (1987) Motor responses of autoimmune NZB/B1NJ and C57BL/6Nnia mice to arecoline and nicotine. Pharmacol Biochem Behav 28:275-82 |
