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The Effects of Cardiotrophin-1 on Early Synaptic Mitochondrial Dysfunction and Synaptic Pathology in APPswe/PS1dE9 Mice.
J Alzheimers Dis. 2017; 59(4):1255-1267.JA

Abstract

The coexistence of neuronal mitochondrial pathology and synaptic dysfunction is an early pathological feature of Alzheimer's disease (AD). Cardiotrophin-1 (CT-1) has been shown to exhibit impressive neuroprotective effects. Previous studies have shown positive effects of CT-1 on brain glucose metabolism and cognition in APPswe/PS1dE9 transgenic mice; however, little is known about the effects of CT-1 on early synaptic mitochondrial dysfunction and resultant synaptic pathology in the brain. In this study, 4-month-old transgenic mice with brain tissue-specific CT-1 expression were used alone or in combination with APPswe/PS1dE9 transgenic mice to evaluate the effect of CT-1 on synaptic mitochondrial dysfunction and resultant synaptic pathology, and cryptic memory deficits in the APPswe/PS1dE9 transgenic mice. The potential mechanism of action of CT-1 was also examined. Young CT-1×APPswe/PS1dE9 transgenic mice exhibited improvements in long-term learning and memory ability and ameliorations of synaptic mitochondrial/synaptic impairments compared to young APPswe/PS1dE9 transgenic mice. Moreover, CT-1 upregulated the expression of AMPAR and increased AMP-activated protein kinase (AMPK) activity in the hippocampus of APPswe/PS1dE9 transgenic mice. However, AMPK inhibition through shRNA knockdown of AMPKα blocked the neuroprotective effects of CT-1 on the expression of AMPAR and mitochondrial/synaptic dysfunction in Aβ-treated mouse neurons. These results suggest that CT-1 may be a potent candidate for the early prevention and treatment of AD.

Authors+Show Affiliations

Department of Pathogen Biology, Medical College, Henan University of Science and Technology, Luolong District, Luoyang, China.Department of Immunology, Medical College, Henan University of Science and Technology, Luolong District, Luoyang, China.College of Animal Science and Technology, Henan University of Science and Technology, Luolong District, Luoyang, China.Department of Biochemistry and Molecular Biology, Medical College, Henan University of Science and Technology, Luolong District, Luoyang, China.Department of Pathogen Biology, Medical College, Henan University of Science and Technology, Luolong District, Luoyang, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28731433

Citation

Wang, Dongmei, et al. "The Effects of Cardiotrophin-1 On Early Synaptic Mitochondrial Dysfunction and Synaptic Pathology in APPswe/PS1dE9 Mice." Journal of Alzheimer's Disease : JAD, vol. 59, no. 4, 2017, pp. 1255-1267.
Wang D, Liu X, Liu Y, et al. The Effects of Cardiotrophin-1 on Early Synaptic Mitochondrial Dysfunction and Synaptic Pathology in APPswe/PS1dE9 Mice. J Alzheimers Dis. 2017;59(4):1255-1267.
Wang, D., Liu, X., Liu, Y., Li, S., & Wang, C. (2017). The Effects of Cardiotrophin-1 on Early Synaptic Mitochondrial Dysfunction and Synaptic Pathology in APPswe/PS1dE9 Mice. Journal of Alzheimer's Disease : JAD, 59(4), 1255-1267. https://doi.org/10.3233/JAD-170100
Wang D, et al. The Effects of Cardiotrophin-1 On Early Synaptic Mitochondrial Dysfunction and Synaptic Pathology in APPswe/PS1dE9 Mice. J Alzheimers Dis. 2017;59(4):1255-1267. PubMed PMID: 28731433.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Effects of Cardiotrophin-1 on Early Synaptic Mitochondrial Dysfunction and Synaptic Pathology in APPswe/PS1dE9 Mice. AU - Wang,Dongmei, AU - Liu,Xiaozhuan, AU - Liu,Yumei, AU - Li,Sanqiang, AU - Wang,Chenying, PY - 2017/7/22/pubmed PY - 2018/4/13/medline PY - 2017/7/22/entrez KW - AMPK KW - Alzheimer’s disease KW - CT-1 KW - mitochondrial pathology KW - synaptic dysfunction SP - 1255 EP - 1267 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 59 IS - 4 N2 - The coexistence of neuronal mitochondrial pathology and synaptic dysfunction is an early pathological feature of Alzheimer's disease (AD). Cardiotrophin-1 (CT-1) has been shown to exhibit impressive neuroprotective effects. Previous studies have shown positive effects of CT-1 on brain glucose metabolism and cognition in APPswe/PS1dE9 transgenic mice; however, little is known about the effects of CT-1 on early synaptic mitochondrial dysfunction and resultant synaptic pathology in the brain. In this study, 4-month-old transgenic mice with brain tissue-specific CT-1 expression were used alone or in combination with APPswe/PS1dE9 transgenic mice to evaluate the effect of CT-1 on synaptic mitochondrial dysfunction and resultant synaptic pathology, and cryptic memory deficits in the APPswe/PS1dE9 transgenic mice. The potential mechanism of action of CT-1 was also examined. Young CT-1×APPswe/PS1dE9 transgenic mice exhibited improvements in long-term learning and memory ability and ameliorations of synaptic mitochondrial/synaptic impairments compared to young APPswe/PS1dE9 transgenic mice. Moreover, CT-1 upregulated the expression of AMPAR and increased AMP-activated protein kinase (AMPK) activity in the hippocampus of APPswe/PS1dE9 transgenic mice. However, AMPK inhibition through shRNA knockdown of AMPKα blocked the neuroprotective effects of CT-1 on the expression of AMPAR and mitochondrial/synaptic dysfunction in Aβ-treated mouse neurons. These results suggest that CT-1 may be a potent candidate for the early prevention and treatment of AD. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/28731433/The_Effects_of_Cardiotrophin_1_on_Early_Synaptic_Mitochondrial_Dysfunction_and_Synaptic_Pathology_in_APPswe/PS1dE9_Mice_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-170100 DB - PRIME DP - Unbound Medicine ER -