Translationally controlled tumor protein restores impaired memory and altered synaptic protein expression in animal models of dementia
This study describes the effects of translationally controlled tumor protein (TCTP) on mice with memory impairment caused by scopolamine (SCO) administration. Specifically, memory functions and expression levels of hippocampal synaptic proteins in 7- to 12-month-old SCO-treated wild-type (WT-SCO) mi...
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Elsevier
2023-04-01
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Series: | Biomedicine & Pharmacotherapy |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223001452 |
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author | Eun Jung Na Yejin Jeon Hyunju Kim Hye-Sun Kim Kyunglim Lee Hwa-Jung Kim |
author_facet | Eun Jung Na Yejin Jeon Hyunju Kim Hye-Sun Kim Kyunglim Lee Hwa-Jung Kim |
author_sort | Eun Jung Na |
collection | DOAJ |
description | This study describes the effects of translationally controlled tumor protein (TCTP) on mice with memory impairment caused by scopolamine (SCO) administration. Specifically, memory functions and expression levels of hippocampal synaptic proteins in 7- to 12-month-old SCO-treated wild-type (WT-SCO) mice were compared to those of TCTP-overexpressing (TG) and TCTP knocked-down (KD) mice similarly treated with SCO. Passive-avoidance tasks were performed with WT, TG, and KD mice for four weeks after intraperitoneal injection of SCO or saline followed by an acquisition test. After completing behavioral studies, hippocampi of all mice groups were collected and their synaptic protein contents were subjected to Western blotting or immunohistochemical analyses, and compared with those of 5x familial Alzheimer's disease (5xFAD) mice and postmortem AD patients. Results of passive avoidance tests revealed that SCO-induced memory impairment was repaired in TCTP-TG mice, but not in TCTP-KD mice. Hippocampal expression levels of synaptophysin, synapsin-1, and PSD-95 were increased in TCTP-TG mice treated with SCO (TG-SCO) but decreased in TCTP-KD mice treated with SCO (KD-SCO). Decreased levels of TCTP, synaptophysin, and PSD-95 were also found in hippocampi of 5xFAD mice and AD patients. Expression levels of p-CREB/CREB and brain-derived neurotrophic factor (BDNF) in TCTP-TG and TG-SCO mice were similar to or increased compared to those in WT mice, but decreased in TCTP-KD and KD-SCO mice. BDNF immunoreactivity was restored in CA1 regions of hippocampi of TG-SCO mice, but not in KD-SCO mice. These results suggest that TCTP can restore damaged memory in mice possibly through restored synaptic protein expression. |
first_indexed | 2024-04-10T07:14:21Z |
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language | English |
last_indexed | 2024-04-10T07:14:21Z |
publishDate | 2023-04-01 |
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series | Biomedicine & Pharmacotherapy |
spelling | doaj.art-b2d47a46c78c4680828759694d6d86ff2023-02-26T04:26:33ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-04-01160114357Translationally controlled tumor protein restores impaired memory and altered synaptic protein expression in animal models of dementiaEun Jung Na0Yejin Jeon1Hyunju Kim2Hye-Sun Kim3Kyunglim Lee4Hwa-Jung Kim5College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, the Republic of KoreaCollege of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, the Republic of KoreaDepartment of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, the Republic of KoreaDepartment of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, the Republic of Korea; Seoul National University College of Medicine, Bundang Hospital, Sungnam 13620, the Republic of KoreaCollege of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, the Republic of Korea; Corresponding authors.College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, the Republic of Korea; Corresponding authors.This study describes the effects of translationally controlled tumor protein (TCTP) on mice with memory impairment caused by scopolamine (SCO) administration. Specifically, memory functions and expression levels of hippocampal synaptic proteins in 7- to 12-month-old SCO-treated wild-type (WT-SCO) mice were compared to those of TCTP-overexpressing (TG) and TCTP knocked-down (KD) mice similarly treated with SCO. Passive-avoidance tasks were performed with WT, TG, and KD mice for four weeks after intraperitoneal injection of SCO or saline followed by an acquisition test. After completing behavioral studies, hippocampi of all mice groups were collected and their synaptic protein contents were subjected to Western blotting or immunohistochemical analyses, and compared with those of 5x familial Alzheimer's disease (5xFAD) mice and postmortem AD patients. Results of passive avoidance tests revealed that SCO-induced memory impairment was repaired in TCTP-TG mice, but not in TCTP-KD mice. Hippocampal expression levels of synaptophysin, synapsin-1, and PSD-95 were increased in TCTP-TG mice treated with SCO (TG-SCO) but decreased in TCTP-KD mice treated with SCO (KD-SCO). Decreased levels of TCTP, synaptophysin, and PSD-95 were also found in hippocampi of 5xFAD mice and AD patients. Expression levels of p-CREB/CREB and brain-derived neurotrophic factor (BDNF) in TCTP-TG and TG-SCO mice were similar to or increased compared to those in WT mice, but decreased in TCTP-KD and KD-SCO mice. BDNF immunoreactivity was restored in CA1 regions of hippocampi of TG-SCO mice, but not in KD-SCO mice. These results suggest that TCTP can restore damaged memory in mice possibly through restored synaptic protein expression.http://www.sciencedirect.com/science/article/pii/S0753332223001452TCTP transgenicTCTP knockdownScopolamine-induced dementiaMemorySynaptic proteins |
spellingShingle | Eun Jung Na Yejin Jeon Hyunju Kim Hye-Sun Kim Kyunglim Lee Hwa-Jung Kim Translationally controlled tumor protein restores impaired memory and altered synaptic protein expression in animal models of dementia Biomedicine & Pharmacotherapy TCTP transgenic TCTP knockdown Scopolamine-induced dementia Memory Synaptic proteins |
title | Translationally controlled tumor protein restores impaired memory and altered synaptic protein expression in animal models of dementia |
title_full | Translationally controlled tumor protein restores impaired memory and altered synaptic protein expression in animal models of dementia |
title_fullStr | Translationally controlled tumor protein restores impaired memory and altered synaptic protein expression in animal models of dementia |
title_full_unstemmed | Translationally controlled tumor protein restores impaired memory and altered synaptic protein expression in animal models of dementia |
title_short | Translationally controlled tumor protein restores impaired memory and altered synaptic protein expression in animal models of dementia |
title_sort | translationally controlled tumor protein restores impaired memory and altered synaptic protein expression in animal models of dementia |
topic | TCTP transgenic TCTP knockdown Scopolamine-induced dementia Memory Synaptic proteins |
url | http://www.sciencedirect.com/science/article/pii/S0753332223001452 |
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