Abstract
Alzheimer’s disease (AD) is the most prevalent form of dementia worldwide. AD is characterized by mild cognitive impairment at onset, irreversibly progressing with age to severe neurodegeneration and cognitive deficits in the late stages. Unfortunately, no effective treatments exist to prevent or delay the cognitive symptoms of AD. Studies have shown that DL-3-n-butylphthalide (DL-NBP) alleviates cognitive impairment induced by amyloid-β in mice by reducing oxidative stress, inhibiting apoptosis, and decreasing tau phosphorylation. In this study, we examined the effects of DL-NBP administration on cognitive function in the senescence-accelerated mouse prone 8 (SAMP8) model of age-related dementia. DL-NBP treatment for 3 months alleviated cognitive impairment in SAMP8 mice as assessed by performance in the Morris water maze test. Moreover, DL-NBP significantly increased the expression of synaptophysin and postsynaptic density protein 95 in the hippocampus of SAMP8 mice, indicative of a protective effect on hippocampal structural synaptic plasticity. In addition, brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling, previously shown to promote synaptic plasticity, was significantly enhanced by the DL-NBP administration. Our findings suggest that DL-NBP is a potential drug candidate for the treatment of cognitive impairment in AD and may serve as the foundation for further research into the development of AD drugs.
Highlights
Alzheimer’s disease (AD) is a destructive and burdensome age-dependent neurodegenerative disorder characterized by mild cognitive impairment at onset and irreversible neurodegeneration and dementia in the late stages (Gainotti et al, 2014)
Because DL-NBP reduced the cognitive decline in senescence-accelerated mouse prone 8 (SAMP8) mice as assessed by the Morris water maze (MWM) test, we evaluated the levels of hippocampal synaptic proteins forming the structural basis of synaptic plasticity in learning and memory
We investigated the effects of DL-NBP treatment on Brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling in the hippocampus of SAMP8 mice
Summary
Alzheimer’s disease (AD) is a destructive and burdensome age-dependent neurodegenerative disorder characterized by mild cognitive impairment at onset and irreversible neurodegeneration and dementia in the late stages (Gainotti et al, 2014). The senescence-accelerated mouse (SAM), developed by Professor Toshio Takeda at Kyoto University, is an accelerated-aging model based on aging instead of gene mutation (Takeda et al, 1997). The SAM consists of the senescence-accelerated mouse prone (SAMP) and senescence-accelerated mouse resistant (SAMR) strains. SAMR1 mice age normally, while the SAMP8, a substrain of the SAMP, shows early-onset irreversible aging following a normal. Because 95% of AD cases are sporadic, have multiple causes, and occur in patients aged ≥65 years, the SAMP8 strain provides a useful model of AD and other age-related human diseases (Pallas et al, 2008)
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