Translationally controlled tumor protein restores memory and synaptic function lost in animal models of dementia

Abstract

Background: The diverse roles of ubiquitously present translationally controlled tumor protein (TCTP) have been well delineated in several organs, but its possible function in the brain, especially with regard to memory function, has not received much attention. This study describes the effects of TCTP on mice with memory impaired by scopolamine (SCO) administration. Specifically, the memory and synaptic functions of 7- and 12-month-old SCO-treated wild mice (WT) were compared with those of TCTP-overexpressing (TG) and TCTP knocked down (KD) mice. Methods: Passive-avoidance tasks were performed on WT, TG and KD mice for 4 weeks after intraperitoneal injection with SCO (1 mg/kg) or saline (CON). After completion of the behavioral studies, the hippocampi were collected and their PSD-95, synapsin-1 and synaptophysin contents analyzed by western blocking and immunohistochemical analyses, and compared with those of 5xfamilial Alzheimer's disease (5xFAD) mice and postmortem AD patients. Results: The SCO-induced memory impairment was restored in TCTP-TG to that of WT level, but not in KD. Hippocampal expression of PSD-95, synapsin-1, and synaptophysin was increased in TG-SCO but decreased in KD-SCO mice. The decreased levels of TCTP, PSD-95, and synaptophysin were also found in the hippocampi of 5xFAD mice and AD patients. PSD-95 immunoreactivity increased particularly in dentate gyrus and CA1 in TCTP-TG, but reduced in KD. The p-CREB/CREB and brain-derived neurotrophic factor (BDNF) expressions also increased in TCTP-TG but dramatically decreased in KD. Conclusion: TCTP restores damaged memory in mice possibly by increasing synaptic function. Keywords TCTP, transgenic, knockdown, scopolamine-induced dementia, memory, synaptic function, PSD-95, synaptophysin, synapsin-1, CREB, BDNF