Intracerebroventricular injection of beta-amyloid in mice is associated with long-term cognitive impairment in the modified hole-board test.

BACKGROUND

The intracerebroventricular injection of beta-amyloid (Aβ) in mice allows the investigation of acute effects on cognitive function and cellular pathology. The aim of this investigation was to further characterize the time course of Aβ-induced cognitive and behavioural changes and to detect potential molecular mechanisms.

METHODS

Cannulas were implanted in the lateral cerebral ventricle. 14days after surgery the mice were injected with Aβ1-42 or phosphate buffered saline (PBS). Starting 2, 4 or 8 (PBS only 4) days after injection we evaluated cognitive and behavioural performance using the modified hole board test (mHBT). We determined tumour-necrosis factor alpha (TNF alpha) and caspase 3 by western blotting, on days 10, 12 and 16. Data were analysed using general linear modelling, Kruskall-Wallis and Mann-Whitney-U test.

RESULTS

Aβ induced a decline in cognitive performance represented as an increased total number of wrong choices during the testing period from day 2-15 (p<0.05). Behavioural parameters were comparable between mice treated with Aβ and PBS. There was no difference regarding TNF alpha levels between the groups. Compared to day 16 Caspase 3 levels were increased on day 10 (p=0.004).

CONCLUSIONS

Application of Aβ in the lateral ventricle of mice is associated with cognitive impairment of declarative memory in the mHBT. There is no interference caused by altered behaviour. Therefore, it represents a valid model for acute Aβ-mediated neurotoxic effects. Although the exact mechanisms remain unclear, changes in levels of Caspase 3 suggest apoptosis as an important factor for the development of cognitive dysfunction.