Reversal of cognitive deficit of apolipoprotein E knockout mice after repeated exposure to a common environmental experience
Section snippets
Animals
ApoE0/0 mice were generated as described previously by interbreeding heterozygous mutants to obtain mice homozygous for the disrupted APOE allele (van Ree et al., 1994) and backcrossed to C57Bl/6J for nine generations. Male apoE0/0 mice and wild-type controls (apoE+/+ siblings) were bred and housed under SPF conditions in the transgenic animal facilities of TNO, Leiden, the Netherlands. At 4–5 months of age, mice were transported to our department and allowed to acclimatise to their new
Water maze performance under basal conditions
Naive apoE0/0 mice are impaired in their spatial learning abilities (genotype F(1, 36)=4.22, P<0.05). After 17 training trials (day 3), apoE0/0 mice still have latencies of 40 s, while wild-type mice reached the platform within 12 s (Fig. 2A). The difference in spatial learning is also reflected in the search strategy used to locate the submerged platform. When cumulative distances to the platform are tracked with image analysis software, specific swim patterns can be distinguished, that can
Discussion
The present study demonstrates that apoE genotype differences in spatial learning as well as basal and stress-induced corticosterone secretion were eliminated after repeated exposure of mice to a common environmental experience: exposure to a rat. Although rats and mice partly share the same environment in nature, they usually avoid each other (Claassen, 1994, Linthorst et al., 2000). The corticosterone responses indeed clearly demonstrate that the encounter of mice with a rat is a stressful
Conclusion
Repeated exposure to rats abolished the differences in basal morning corticosterone, the corticosterone response to novelty and the cognitive performance between apoE0/0 and wild-type mice: apoE0/0 mice improved, while wild-types became impaired in water maze performance. This effect exerted by repeated stress appears to be mediated by corticosterone and depends on the presence of apoE.
Acknowledgements
This study was supported by the Internationale Stichting Alzheimer Onderzoek (ISAO, #679756-0270), the Netherlands Organisation for Scientific Research (NWO, #970-10-007 and #903-43-132) and EC BiotecPL960179. The technical assistance of Maaike Kempes, Leo Enthoven, Paul Lucassen and Marc Fluttert is gratefully acknowledged.
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