Affiliations: [a] Department of Pathogen Biology, Medical College, Henan University of Science and Technology, Luolong District, Luoyang, China
| [b] Department of Immunology, Medical College, Henan University of Science and Technology, Luolong District, Luoyang, China
| [c] College of Animal Science and Technology, Henan University of Science and Technology, Luolong District, Luoyang, China
| [d] Department of Biochemistry and Molecular Biology, Medical College, Henan University of Science and Technology, Luolong District, Luoyang, China
Correspondence:
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Correspondence to: Dongmei Wang, Department of Pathogen Biology, Medical College, Henan University of Science and Technology, No. 263, Kaiyuan Avenue, Luolong District, Luoyang, 471023 P. R. China. E-mail: [email protected].
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.
