TY - JOUR
T1 - Transgenic mice overexpressing the neurotrophic factor S-100β show neuronal cytoskeletal and behavioral signs of altered aging processes
T2 - Implications for Alzheimer's disease and Down's syndrome
AU - Whitaker-Azmitia, Patricia M.
AU - Wingate, Michael
AU - Borella, Alice
AU - Gerlai, Robert
AU - Roder, John
AU - Azmitia, Efrain C.
N1 - Funding Information:
This work has been supported by a program project grant from the National Institute on Aging. The authors wish to express their appreciation to Dr. Luisa Gregori for helpful suggestions.
PY - 1997/11/21
Y1 - 1997/11/21
N2 - S-100β is a neurotrophic factor released by astroglial cells and localized to chromosome 21, within the region which is considered obligate for Down's syndrome (DS). S-100β is increased in the postmortem brains of both DS and Alzheimer's disease. Transgenic mice, produced by insertion of the human gene for S-100β, were examined for dendritic development at two ages, using an antibody against microtubule associated protein-2 (MAP-2). At the earliest stages, the density of dendrites 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 loss of dendrites compared to controls and the number of cells showing cell body staining was further increased. These pathological changes could be indicative of the presence of neurofibrillary tangles and cytoskeletal collapse. Behaviorally, younger transgenic animals could not perform in a learning task as well as controls. Together, these findings suggest that increased S-100β in brain may lead to accelerated development, followed by increased aging. The pathological changes may prove useful as an animal model of Down's syndrome and Alzheimer's disease.
AB - S-100β is a neurotrophic factor released by astroglial cells and localized to chromosome 21, within the region which is considered obligate for Down's syndrome (DS). S-100β is increased in the postmortem brains of both DS and Alzheimer's disease. Transgenic mice, produced by insertion of the human gene for S-100β, were examined for dendritic development at two ages, using an antibody against microtubule associated protein-2 (MAP-2). At the earliest stages, the density of dendrites 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 loss of dendrites compared to controls and the number of cells showing cell body staining was further increased. These pathological changes could be indicative of the presence of neurofibrillary tangles and cytoskeletal collapse. Behaviorally, younger transgenic animals could not perform in a learning task as well as controls. Together, these findings suggest that increased S-100β in brain may lead to accelerated development, followed by increased aging. The pathological changes may prove useful as an animal model of Down's syndrome and Alzheimer's disease.
KW - Alzheimer's disease
KW - Dendrite
KW - Down's syndrome
KW - Hippocampus
KW - MAP-2
KW - Neurofibrillary tangle
KW - Neuronal cytoskeleton
KW - S-100β
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U2 - 10.1016/S0006-8993(97)01002-0
DO - 10.1016/S0006-8993(97)01002-0
M3 - Article
C2 - 9439795
AN - SCOPUS:0031446195
SN - 0006-8993
VL - 776
SP - 51
EP - 60
JO - Brain Research
JF - Brain Research
IS - 1-2
ER -