The Effects of Cardiotrophin-1 on Early Synaptic Mitochondrial Dysfunction and Synaptic Pathology in APPswe/PS1dE9 Mice

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.

A serum protein signature of APOE genotypes in centenarians

“…Another secreted protein that appears to be upregulated in carriers of the e 4 allele is cardiotrophin‐1 (CTF1). This result is surprising since two separate papers found overexpression of this gene to be protective in mice models of Alzheimer's (Wang et al, ; Wang, Liu, Liu, Li, & Wang, ). Our findings do not suggest this, although of course the upregulation might be "compensatory."…”

Ameliorative Effects of Arctigenin From Arctium Lappa L Against LPS-induced Neuroinflammation and Cognitive Impairments in Mice

“…Immuno uorescence staining was carried out on brain and cell slices as previously described (Wang et al 2017b(Wang et al , 2019. Following blocking in 10% goat serum at room temperature for 1 h,the slideswere incubated with the primary antibodies: Synapsin-1 (1:200; Cell Signaling Technology), PSD95 (1:300; Millipore), Aβ (1:200; Cell Signaling Technology), and NF-κB p65 (1:200; Cell Signaling Technology) at 4°C overnight.…”