Here, we combine APPswe/PS1dE9 (APP/PS1) mice with the cholinergic immunotoxin mu p75-saporin (SAP) to integrate partial basal forebrain cholinergic degeneration and the neuropathology of APP/PS1 mice. By 6 months of age, APP/PS1 mice and p38 MAPK activity wild type littermates (Wt) received intracerebroventricular injection of 0.6 mu g SAP (lesion) or PBS (sham). Two months following surgery, APP/PS1 mice treated with SAP were significantly
impaired compared to sham treated APP/PS1 mice in a behavioural paradigm addressing working memory. Conversely, the performance of Wt mice was unaffected by SAP treatment. Choline acetyltransferase activity was reduced in the hippocampus and frontal cortex following SAP treatment. The selective effect of a mild SAP lesion in APP/PS1 mice was not due to a more extensive cholinergic degeneration since the reduction in choline acetyltransferase activity was similar following SAP treatment in APP/PS1 mice and Wt. Interestingly, plague load was significantly increased in SAP treated APP/PS1 mice relative to sham lesioned APP/PS1 mice. Additionally, APP/PS1 mice treated with SAP showed a tendency towards an increased level of soluble and insoluble A beta 1-40 and A beta 1-42 measured in brain tissue homogenate. Our results suggest that
the combination of cholinergic degeneration and A beta overexpression Cytoskeletal Signaling inhibitor in the APP/PS1 mouse model results in cognitive decline and accelerated plague burden. SAP treated APP/PS1 mice might thus constitute an improved model of Alzheimer’s disease-like neuropathology and cognitive deficits compared to the conventional APP/PS1 model without selective removal of basal forebrain cholinergic neurons. (C) 2012 Elsevier B.V. All rights reserved.”
“An increase in the occurrence of sudden
local flooding of great volume and short duration has caused significant danger and loss of life and property in Korea as well as many other parts of the World. Since such floods usually accompanied by rapid runoff and debris flow rise quite quickly with little or no advance warning to prevent EPZ5676 supplier flood damage, this study presents a new flash flood indexing methodology to promptly provide preliminary observations regarding emergency preparedness and response to flash flood disasters in small ungauged catchments. Flood runoff hydrographs are generated from a rainfall-runoff model for the annual maximum rainfall series of long-term observed data in the two selected small ungauged catchments. The relative flood severity factors quantifying characteristics of flood runoff hydrographs are standardized by the highest recorded maximum value, and then averaged to obtain the flash flood index only for flash flood events in each study catchment.