Fig. 6.

TFP5 inhibits NMDA-induced cdk5/p25 activation in mouse hippocampal slices. A) Hippocampal slices from 3 to 5- month-old WT mice were pre-incubated with TFP5 or scrambled peptide (100 nM) for 30 min followed by cLTD induction (NMDA 50 μM for 5 min and recovery for 15 min), and then subjected to cdk5 kinase assay (n = 5 from 3 mice). Control: 100 ± 10.1, Scrambled + NMDA: 138.2 ± 7.3, TFP5 + NMDA 92.7 ± 10.0, ANOVA test; p = 0.0097 with post hoc Tukey HSD. B) Cdk5 activity in hippocampal slices from the Dp35KI calpain-resistant mutant, that fails to produce p25 endogenously or after stimulation, is significantly unaffected by TFP5 treatment. Slices were preincubated with TFP5 (100 nM for 30 min), then subjected to a kinase assay after cdk5 immunoprecipitation, Activity, though slightly less than the untreated control activity, was not significant (n = 3, p < 0.44 with post hoc Tukey). This is consistent with observations showing that endogenous brain cdk5/p35 is not inhibited by TFP5.