The rats with TMT injection showed impaired learning and memory of the tasks and treatment with TF produced a significant improvement of the escape latency to find the platform in the Morris water maze compared to that of the control group. In the retention test, the TF50 group showed increased time spent around the platform compared to that of the control group. Consistent with the behavioral data, TF50 mg/kg significantly alleviated the loss of ChAT-ir neurons in the hippocampus compared to that of the control group. Treatment with TF significantly increased the CREB positive neurons in the hippocampal CA1 area as compared to that of the control group. In addition, TF treatment (50 mg/kg) increased the glucose uptake approximately sevenfold in the frontal lobe and it significantly promoted neurite outgrowth of the PC12 cells, as compared to that of the controls.
These results suggest that TF may be useful for improving the cognitive function via regulation of the CREB signaling pathway and cholinergic system in the hippocampus.