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P4‐194: Modulation of endogenous TGF‐β1 reduces microglial proliferation and Aβ deposition in a mouse model of Alzheimer's disease
Author(s) -
Ng Vivian,
Gelinas David,
Brown Mary,
McLaurin JoAnne
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.761
Subject(s) - microglia , transforming growth factor , macrophage , microbiology and biotechnology , transforming growth factor beta , biology , amyloid (mycology) , alzheimer's disease , chemistry , endocrinology , immunology , neuroscience , medicine , inflammation , biochemistry , disease , in vitro , botany
Background: Loss of basal forebrain cholinergic neurons and their axonal projections to the cortex and the hippocampus is thought to underlie some of the cognitive deficits observed in Alzheimer’s disease. Belluci et al. (2006) reported a decrease in the number of choline acetyltransferase (ChAT)-positive neurons in the nucleus basalis magnocellularis in 7month-old TgCRND8 mice. Basaland potassium-stimulated acetylcholine levels were also reduced in concert with cognitive deficits. McLaurin et al. (2006) found that treating TgCRND8 mice with scyllo-inositol, ELND005, attenuates amyloid pathology and prevents Abeta-induced cognitive deficits related to hippocampal function. We investigated whether the cholinergic septohippocampal pathway degenerates and whether adult hippocampal neurogenesis is decreased in TgCRND8 mice due to the accumulation of Abeta or the overexpression of APP. Methods: TgCRND8 mice were treated orally with scyllo-inositol. The cholinergic system was investigated through ChAT activity assays, and quantification of cholinergic cell numbers in the medial septal nucleus by design-based stereology. To assess the effects of scyllo-inositol on adult neurogenesis, we quantified the number of bromodeoxyuridine (BrdU)and neuronal-specific nuclear protein (NeuN)-positive cells in aged TgCRND8 mice. Results: Data suggests that treatment with scyllo-inositol prevents Abeta-induced reductions in ChAT activity. The number of ChAT-positive cells in the medial septal nucleus appears to be protected with scyllo-inositol treatment. In young mice, BrdU-positive cell numbers were increased in the subgranular zone of the dentate gyrus of untreated TgCRND8 mice over non-transgenic littermates. With aging, both transgenic and non-transgenic mice showed a statistically significant decrease in BrdU-positive cell number. The influence of scyllo-inositol on adult neurogenesis is currently being investigated. Conclusions: Our data indicate that scyllo-inositol, ELND005, protects cholinergic neurons from degenerating in the septal nucleus.