Expression of p25 impairs contextual learning but not latent inhibition in mice.
The cyclin-dependent kinase 5 activator p25, which is derived from cleavage of p35, is thought to be formed in the brain of patients with Alzheimer's disease and schizophrenia. Female, but not male, transgenic mice expressing low levels of p25 have enhanced hippocampal long-term potentiation and improved spatial learning, raising the hypothesis that p25 may compensate for early learning deficits in Alzheimer's disease in a sex-dependent manner. Here, we show that low levels of p25 do not alter latent inhibition, a phenomenon that is impaired in patients with schizophrenia. We also demonstrate that contextual fear conditioning is impaired in female, but not in male, p25 transgenic mice. Thus, low levels of p25 are not always beneficial for learning as was previously hypothesized.
Mizuno
Keiko
K
Wolfson Institute for Biomedical Research, University College London, London, UK.
Plattner
Florian
F
Peter Giese
K
K
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004597:Electroshock / Q000009:adverse effects; D005239:Fear; D015870:Gene Expression / Q000235:genetics*; D007266:Inhibition, Psychological; D007858:Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010770:Phosphotransferases; D012737:Sex Factors
C492236:Cdk5r1 protein, mouse; D009419:Nerve Tissue Proteins; D010770:Phosphotransferases