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Long‐term basal forebrain cholinergic‐rich graftsderived from trisomy 16 mice do not develop β ‐AMYLOID pathology and neurodegeneration butdemonstrate neuroinflammatory responses
Author(s) -
Stahl Tobias,
Goldammer Axel,
Luschekina Elena,
Beck Mike,
Schliebs Reinhard,
Bigl Volker
Publication year - 1998
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/s0736-5748(98)00085-9
Subject(s) - neurodegeneration , basal forebrain , biology , trisomy , pathology , cholinergic neuron , amyloid precursor protein , alzheimer's disease , cholinergic , neuroscience , medicine , genetics , disease
Patients with Down syndrome (human trisomy 21) develop neuropathological andcholinergic functional defects characteristic of Alzheimers disease, which has been attributed tothe location of the Alzheimer β ‐amyloid precursor protein on chromosome 21. Due tothe partial genetic homology between mouse chromosome 16 and human chromosome 21, murinetrisomy 16 was used as a model to study functional links between increased expression of theamyloid precursor protein, neurodegeneration and neuroinflammatory responses. Basal forebraincholinergic‐rich tissue derived from trisomy 16 mice at embryonic age of day 16 was transplantedinto the lateral ventricle of adult normal mice. At 1, 3, 6, 9 and 12 months after transplantation,the grafts were characterized by immunocytochemistry, molecular biological analysis, andstereological methods. Grafts survived up to one year and still demonstrated immunoreactivity forcholinergic, GABAergic and astroglial cells. Though a 1.5‐fold neuronal overexpression ofamyloid precursor protein was detected in brains from trisomy 16 embryos by Northern analysis, β ‐amyloid deposits were found neither in control nor trisomic grafts. Detailedstereological analysis of trisomic grafts did not reveal any neurodegeneration or morphologicalchanges of cholinergic and GABAergic neurons during the course of graft maturation up to oneyear, as compared to grafts derived from euploid tissue. However, both euploid and trisomicgrafts demonstrated a strong infiltration with T‐ and B‐lymphocytes and a significant micro‐ andastroglial activation (hypertrophic astrocytes) within and around the grafts. These observationsfurther suggest that the trisomy 16‐induced neurodegeneration is seemingly due to a lack ofneuron supporting factors which are provided by either the metabolic interaction of trisomic graftwith surrounding healthy host tissue or by cells of the immune system infiltrating the graft.