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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. [ABSTRACT FROM AUTHOR]

Bioflavonoids are being utilised as neuroprotectants in the treatment of various neurological disorders, including Alzheimer's disease (AD). Astilbin, a bioflavanoid, has been reported to have potent neuroprotective effects, but its preventive effects on amyloid-β (Aβ)-induced, Alzheimer's disease-related, cognitive impairment, and the underlying mechanisms of these effects have not been well characterised. Five-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group and two astilbin (either 20 or 40 mg/kg per day, intraperitoneally) groups. After 8 weeks of treatment, we observed beneficial effects of astilbin (40 mg/kg per day), including lessening learning and memory deficits and reducing plaque burden and Aβ levels. Furthermore, the expressions of both the cAMP responsive element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were significantly increased and the disturbance of AKT/GSK-3β signalling pathway was markedly ameliorated in the hippocampus of astilbin-treated (40 mg/kg per day) group. Our data suggest that astilbin might be a potential therapeutic agent against AD. [ABSTRACT FROM AUTHOR]