TRANSGENIC MICE OVEREXPRESSING THE NEUROTROPHIC FACTOR S-100-BETA SHOW NEURONAL CYTOSKELETAL AND BEHAVIORAL SIGNS OF ALTERED AGING PROCESSES - IMPLICATIONS FOR ALZHEIMERS-DISEASE AND DOWNS-SYNDROME
Pm. Whitakerazmitia et al., TRANSGENIC MICE OVEREXPRESSING THE NEUROTROPHIC FACTOR S-100-BETA SHOW NEURONAL CYTOSKELETAL AND BEHAVIORAL SIGNS OF ALTERED AGING PROCESSES - IMPLICATIONS FOR ALZHEIMERS-DISEASE AND DOWNS-SYNDROME, Brain research, 776(1-2), 1997, pp. 51-60
S-100 beta is a neurotrophic factor released by astroglial cells and l
ocalized to chromosome 21, within the region which is considered oblig
ate for Down's syndrome (DS). S-100 beta is increased in the postmorte
m brains of both DS and Alzheimer's disease. Transgenic mice, produced
by insertion of the human gene for S-100 beta, were examined for dend
ritic development at two ages, using an antibody against microtubule a
ssociated protein-2 (MAP-2). At the earliest stages, the density of de
ndrites within the hippocampus of transgenic animals exceeded that of
controls. Also, MAP-2 immunostaining was evident in the region of the
cell body. By 1 year of age, the transgenic animals had significant lo
ss of dendrites compared to controls and the number of cells showing c
ell body staining was further increased. These pathological changes co
uld be indicative of the presence of neurofibrillary tangles and cytos
keletal collapse. Behaviorally, younger transgenic animals could not p
erform in a learning task as well as controls. Together, these finding
s suggest that increased S-100 beta in brain may lead to accelerated d
evelopment, followed by increased aging. The pathological changes may
prove useful as an animal model of Down's syndrome and Alzheimer's dis
ease. (C) 1997 Elsevier Science B.V.