Abstract
The Amyloid-β (Aβ)-induced impairment of hippocampal synaptic plasticity is an underlying mechanism of memory loss in the early stages of Alzheimer’s disease (AD) in human and mouse models. The inhibition of the calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation plays an important role in long-term memory. In this study, we isolated naringin from Pomelo peel (a Citrus species) and studied its effect on long-term memory in the APPswe/PS1dE9 transgenic mouse model of AD. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two naringin (either 50 or 100 mg/kg body weight/day) groups, or an Aricept (2 mg/kg body weight/day) group. After 16 weeks of treatment, we observed that treatment with naringin (100 mg/kg body weight/day) enhanced the autophosphorylation of CaMKII, increased the phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor at a CaMKII-dependent site and improved long-term learning and memory ability. These findings suggest that the increase in CaMKII activity may be one of the mechanisms by which naringin improves long-term cognitive function in the APPswe/PS1dE9 transgenic mouse model of AD.
Highlights
Alzheimer’s disease (AD) is a degenerative neurological disease that is clinically characterized by progressive cognitive dysfunction [1]
The standard treatment for symptomatic AD relies primarily on acetyl-cholinesterase (AChE) inhibitors and Aricept-treated group (Aricept) is an example of an AChE inhibitor; only a modest effect on the rate of degeneration is afforded by memantine, a glutamate receptor antagonist [4]
We evaluated the effect of purified naringin on long-term cognitive function
Summary
Alzheimer’s disease (AD) is a degenerative neurological disease that is clinically characterized by progressive cognitive dysfunction [1]. Previous studies have shown that early synaptic dysfunction caused by the accumulation of Aβ may initiate synapse loss, cell death, and cognitive impairment in AD [5,6] and may be fully reversible if the appropriate intervention occurs. A key question to be answered is how Aβ at this stage affects synaptic plasticity in the neuronal networks where memories are formed and stored. Recent epidemiological and dietary interventional studies, both in humans and animals, suggest that these flavonoids prevent and delay neurodegeneration, especially in aged-population cognitive dysfunction [9]. Little information is available in the literature about the effect of naringin on Aβ-induced long-term cognitive impairment. We isolated naringin from Pomelo peel and studied the effects of naringin on long-term memory and CaMKII activity in the APPswe/PS1dE9 transgenic mouse model of Alzheimer’s disease
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