Transgenic mice overexpressing the neurotrophic factor S-100β show neuronal cytoskeletal and behavioral signs of altered aging processes

Implications for Alzheimer's disease and Down's syndrome

Patricia M. Whitaker-Azmitia, Michael Wingate, Alice Borella, Robert Gerlai, John Roder, Efrain C. Azmitia

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)51-60
Number of pages10
JournalBrain Research
Volume776
Issue number1-2
DOIs
StatePublished - Nov 21 1997

Fingerprint

Genetically Modified Animals
Nerve Growth Factors
Down Syndrome
Transgenic Mice
Alzheimer Disease
Microtubule-Associated Proteins
Dendrites
Chromosomes, Human, Pair 21
Neurofibrillary Tangles
Insertional Mutagenesis
Brain
Hippocampus
Animal Models
Cell Count
Learning
Staining and Labeling
Antibodies
Cell Body

Keywords

  • Alzheimer's disease
  • Dendrite
  • Down's syndrome
  • Hippocampus
  • MAP-2
  • Neurofibrillary tangle
  • Neuronal cytoskeleton
  • S-100β

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Transgenic mice overexpressing the neurotrophic factor S-100β show neuronal cytoskeletal and behavioral signs of altered aging processes : Implications for Alzheimer's disease and Down's syndrome. / Whitaker-Azmitia, Patricia M.; Wingate, Michael; Borella, Alice; Gerlai, Robert; Roder, John; Azmitia, Efrain C.

In: Brain Research, Vol. 776, No. 1-2, 21.11.1997, p. 51-60.

Research output: Contribution to journalArticle

@article{48643d83340e4cb4a399abcc7d1e7181,
title = "Transgenic mice overexpressing the neurotrophic factor S-100β show neuronal cytoskeletal and behavioral signs of altered aging processes: Implications for Alzheimer's disease and Down's syndrome",
abstract = "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.",
keywords = "Alzheimer's disease, Dendrite, Down's syndrome, Hippocampus, MAP-2, Neurofibrillary tangle, Neuronal cytoskeleton, S-100β",
author = "Whitaker-Azmitia, {Patricia M.} and Michael Wingate and Alice Borella and Robert Gerlai and John Roder and Azmitia, {Efrain C.}",
year = "1997",
month = "11",
day = "21",
doi = "10.1016/S0006-8993(97)01002-0",
language = "English (US)",
volume = "776",
pages = "51--60",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1-2",

}

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.

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

UR - http://www.scopus.com/inward/record.url?scp=0031446195&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031446195&partnerID=8YFLogxK

U2 - 10.1016/S0006-8993(97)01002-0

DO - 10.1016/S0006-8993(97)01002-0

M3 - Article

VL - 776

SP - 51

EP - 60

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1-2

ER -