PSAPP mice exhibit regionally selective reductions in gliosis and plaque deposition in response to S100B ablation.

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TitlePSAPP mice exhibit regionally selective reductions in gliosis and plaque deposition in response to S100B ablation.
Publication TypeJournal Article
Year of Publication2010
AuthorsRoltsch, E, Holcomb, L, Young, KA, Marks, A, Zimmer, DB
JournalJ Neuroinflammation
Volume7
Pagination78
Date Published2010
ISSN1742-2094
KeywordsAlzheimer Disease, Animals, Astrocytes, Calcium-Binding Proteins, Cerebral Cortex, Disease Models, Animal, Female, Glial Fibrillary Acidic Protein, Gliosis, Hippocampus, Humans, Male, Mice, Mice, Knockout, Mice, Transgenic, Microfilament Proteins, Microglia, Nerve Growth Factors, Neurons, Plaque, Amyloid, S100 Proteins, tau Proteins
Abstract

BACKGROUND: Numerous studies have reported that increased expression of S100B, an intracellular Ca2+ receptor protein and secreted neuropeptide, exacerbates Alzheimer's disease (AD) pathology. However, the ability of S100B inhibitors to prevent/reverse AD histopathology remains controversial. This study examines the effect of S100B ablation on in vivo plaque load, gliosis and dystrophic neurons.

METHODS: Because S100B-specific inhibitors are not available, genetic ablation was used to inhibit S100B function in the PSAPP AD mouse model. The PSAPP/S100B-/- line was generated by crossing PSAPP double transgenic males with S100B-/- females and maintained as PSAPP/S100B+/- crosses. Congo red staining was used to quantify plaque load, plaque number and plaque size in 6 month old PSAPP and PSAPP/S100B-/- littermates. The microglial marker Iba1 and astrocytic marker glial fibrillary acidic protein (GFAP) were used to quantify gliosis. Dystrophic neurons were detected with the phospho-tau antibody AT8. S100B immunohistochemistry was used to assess the spatial distribution of S100B in the PSAPP line.

RESULTS: PSAPP/S100B-/- mice exhibited a regionally selective decrease in cortical but not hippocampal plaque load when compared to PSAPP littermates. This regionally selective reduction in plaque load was accompanied by decreases in plaque number, GFAP-positive astrocytes, Iba1-positive microglia and phospho-tau positive dystrophic neurons. These effects were not attributable to regional variability in the distribution of S100B. Hippocampal and cortical S100B immunoreactivity in PSAPP mice was associated with plaques and co-localized with astrocytes and microglia.

CONCLUSIONS: Collectively, these data support S100B inhibition as a novel strategy for reducing cortical plaque load, gliosis and neuronal dysfunction in AD and suggest that both extracellular as well as intracellular S100B contribute to AD histopathology.

DOI10.1186/1742-2094-7-78
Alternate JournalJ Neuroinflammation
PubMed ID21080947
PubMed Central IDPMC2996465