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P2‐309: Granulocyte‐colony simulating factor reduces hippocampal amyloid load and improves behavioral performance in a transgenic Alzheimer's disease mouse model
Author(s) -
Sanchez-Ramos Juan,
Song Shijie,
Cao Chuanhai,
Lin Xiaoyang,
Mori Takashi,
Arendash Gary
Publication year - 2008
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.2008.05.1386
Subject(s) - bone marrow , granulocyte colony stimulating factor , microglia , genetically modified mouse , green fluorescent protein , amyloid precursor protein , granulocyte , chemistry , hippocampal formation , transgene , endocrinology , medicine , pathology , alzheimer's disease , biochemistry , disease , chemotherapy , gene , inflammation
Based on these, we predicted that decreasing expression of App would increase NGF transport and prevent BFCN degeneration in Ts65Dn mice. In order to test this idea, we have been testing the effects of a small molecule to reduce App expression. Methods: ( )-Phenserine is able to reduce App protein levels in rodents without decreasing App mRNA levels. It is believed that this effect is due to suppression of App translation by interacting with an iron responsive element (IRE) in App mRNA. In a very large (45 pairs) set of 3-month-old Ts65Dn mice and their controls, we tested the effects of long term (21 days) treatment with daily ip injection of two doses of 25 and 50 mg/kg of ( )-phenserine. The mice were weighed daily and injected according to their body weight. At the last day of the experiment, mice were sacrificed 90 minutes after the last injection. The samples taken included the entire brain, cardiac blood, liver and kidneys. The blood samples were centrifuged and the resulting plasma was used for measuring the concentration of ( )-phenserine. Results: Measuring the body weight showed no significant effects of long-term ( )-phenserine treatment on the body weight. In fact there was a significant positive correlation between the body weight and the days of the injection suggesting the treated mice gained weight normally. No significant differences were found in either body or brain weight among the three groups (saline, low dose and high dose). Currently, we are quantifying App protein levels using Western blotting and abeta-40 and 42 using ELISA. Conclusions: Our findings indicate that the use of a drug that targets App expression may be well tolerated and does not lead to any apparent adverse effects. The data for these experiments will be presented. These studies are intended to bring insights bearing on the pathogenesis and treatment of BFCN degeneration in DS.