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P3–347: Brain derived neurotrophic factor (BDNF) mRNA expression is reduced in postmortem hippocampal dentate gyrus in Alzheimer's disease and dementia with lewy bodies
Author(s) -
Raskind Murray A.,
Leverenz James B.,
Peskind Elaine R.,
White Sylvia S.,
Greenup J. Lynne,
Szot Patricia
Publication year - 2006
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.2006.05.1617
Subject(s) - dentate gyrus , hippocampus , hippocampal formation , dementia with lewy bodies , brain derived neurotrophic factor , neurotrophic factors , medicine , psychology , neuroscience , endocrinology , alzheimer's disease , dementia , receptor , disease
disease pathology. Inflammatory mediators were recently identified as potent modulators of neurogenesis. Interestingly, Alzheimer’s disease patients have a higher level of neurogenesis than non-demented individuals (Jin K, 2004); however reports from Alzheimer’s disease mouse models are controversial. Molecular modulators of neurogenesis in Alzheimer’s disease are still unknown. Objective(s): 1. Identify the inflammatory mediators released in aging TgCRND8 mice and wildtype littermates. 2. Identify the level of neurogenesis in aging TgCRND8 mice compared to wild-type littermates and evaluate the impact of highly expressed inflammatory mediator(s) on neurogenesis. Methods and Results: Evaluation of the inflammatory profile of 2-18 month-old TgCRND8 and wild-type mice using RNAse protection assay revealed a significant increase in TGF 1 in 14 and 18 month-old in the cortex and the hippocampus of the TgCRND8 mice, but not in the cerebellum. The levels of pro-inflammatory molecules such as IL-1 , TNF-alpha and IL-6 did not differ between transgenic and wild-type mice at any age. Neurogenesis was measured using BrdU incorporation. BrdU-positive cells were approximately 40% higher in the dentate gyrus of young (6 weeks) and old (14 months) TgCRND8 mice when compared to wild-type mice. Double staining revealed that most of the BrdU-positive cells co-localized with doublecortin a marker for immature neurons. Furthermore, the use of an endogenous marker of cell proliferation ki67 confirmed the increase in cell proliferation in the TgCRND8. The importance of the cytokine TGF 1 will be assessed on the on the neurogenesis level observed in the TgCRND8 mice. Conclusions: The TgCRND8 mouse recapitulates features observed in Alzheimer’s disease patients as TGF 1 and neurogenesis levels are increased.