Authors: E.R DETRAIT, B. DANIS, P. FOERCH, Y. LAMBERTY; UCB pharma S.A., Braine-L’Alleud, Belgium.

 


Abstract: Alzheimer disease has long been associated with increased inflammation in the brain. Activated microglia and increased production of the inflammatory cytokine TNF, have been proposed to contribute to the onset and progression of the disease. We investigated if anti-TNF treatment ameliorates the behavioral symptoms and decrease neuroinflammation in a non-transgenic mouse model mimicking some hallmarks of the disease. Seven days after a single intracebroventricular (icv) injection of aggregated amyloid beta25-35 (9 nmoles) to male Swiss mice significant cognitive deficits in Y-maze and inhibitory avoidance task, as well as increase TNF level in the hippocampus were apparent. Alternation percentage decreased from 72.4% ±1.3 to chance level (52.6% ±1.7); step-through retention latency decreased from 254s ±9 to 144s ±14; and TNF level doubled. Subcutaneous injections of 30mg/kg TNFR-Fc fusion protein was administered three times before behavioral testing (every second day post amyloid beta 25-35 icv administration). This treatment counteracted the amyloid-induced decreased alternation percentage (66.4s ±1.8) and the decrease step-through retention latency (248s ±9), and brought back to control level the elevation of hippocampal TNF induced by amyloid. These data suggest that peripheral administration of TNFR fusion protein counteract amyloid-induced impairment in working and long-term-memory.

2012 Copyright by the Society for Neuroscience all rights reserved.

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