Transgenic mice overexpressing the neurotrophic factor S-100 beta show neuronal cytoskeletal and behavioral signs of altered aging processes: implications for Alzheimer's disease and Down's syndrome.
S-100 beta 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-100 beta is increased in the postmortem brains of both DS and Alzheimer's disease. Transgenic mice, produced by insertion of the human gene for S-100 beta, 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-100 beta 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.
Whitaker-Azmitia
P M
PM
Department of Psychiatry, State University of New York (SUNY), Stony Brook 11794-8101, USA. whittaker@psych1.psy.sunyab.edu
Wingate
M
M
Borella
A
A
Gerlai
R
R
Roder
J
J
Azmitia
E C
EC
D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000235:genetics; D003599:Cytoskeleton / Q000378:metabolism*; D003712:Dendrites / Q000737:chemistry / Q000378:metabolism; D004314:Down Syndrome / Q000378:metabolism*; D005091:Exons; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009414:Nerve Growth Factors; D016874:Neurofibrillary Tangles / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000032:analysis / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology
D002135:Calcium-Binding Proteins; D008869:Microtubule-Associated Proteins; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins