Increased glutamic acid decarboxylase expression in the hippocampus impairs learning and memory in Fmr1 knockout mice

This study compares the behavioral differences in 4- and 6-week-old mice in hippocampal expression of glutamic acid decarboxylase (GAD). Using immunoblotting and immunohistochemical staining, we compared the changed GAD expression in Fmr1 knockout mice. We detected the amino acid levels of hippocampus by high performance liquid chromatography, the data were analyzed with Multifactor Variance Analysis. Fmr1 knock out (KO) mice showed a higher expression of GAD65/67 protein in hippocampus than the Fmr1 wild type (WT) mice (P < 0.05). The six-week KO mice and WT mice exhibited a higher expression of GAD65/67 protein (in hippocampus) than their four-week counterpart (P < 0.05). KO mice showed a higher number of GAD65/67-positive neurons in hippocampus and cortex than the WT mice of the same week (P < 0.05). The six-week KO mice and WT mice contain a greater number of GAD65/GAD67-positive neurons in hippocampus than their four-week counterpart (P < 0.05). The Upsilon-aminobutyric acid and aspartate levels in KO group were lower than WT mice, while the level of glutamate in KO was higher than WT group. Altered GAD protein levels in KO mice may play an important role in their abnormal learning and memory behavior in Fmr1 knockout mice.