期刊
MABS
卷 5, 期 5, 页码 665-677出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/mabs.25424
关键词
Alzheimer disease; scFv; immunotherapy; behavior; amyloid beta oligomers; apoE; apoJ; clusterin
资金
- MAEC-AECI fellowship (Spanish government)
- PIF (UAB, Spain) fellowship
- [FMM-2008]
- [FISPI10-00975]
- [-00265]
- [-00283]
- [SGR2009-00761]
- [-42271]
The single-chain variable fragment, scFv-h3D6, has been shown to prevent in vitro toxicity induced by the amyloid (A) peptide in neuroblastoma cell cultures by withdrawing A oligomers from the amyloid pathway. Present study examined the in vivo effects of scFv-h3D6 in the triple-transgenic 3xTg-AD mouse model of Alzheimer disease. Prior to the treatment, five-month-old female animals, corresponding to early stages of the disease, showed the first behavioral and psychological symptoms of dementia -like behaviors. Cognitive deficits included long- and short-term learning and memory deficits and high swimming navigation speed. After a single intraperitoneal dose of scFv-h3D6, the swimming speed was reversed to normal levels and the learning and memory deficits were ameliorated. Brain tissues of these animals revealed a global decrease of A oligomers in the cortex and olfactory bulb after treatment, but this was not seen in the hippocampus and cerebellum. In the untreated 3xTg-AD animals, we observed an increase of both apoJ and apoE concentrations in the cortex, as well as an increase of apoE in the hippocampus. Treatment significantly recovered the non-pathological levels of these apolipoproteins. Our results suggest that the benefit of scFv-h3D6 occurs at both behavioral and molecular levels.
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