Project Details


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.
Effective start/end date1/01/901/01/90