Long-Term DL-3-n-Butylphthalide Treatment Alleviates Cognitive Impairment Correlate With Improving Synaptic Plasticity in SAMP8 Mice

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.

dl‐3‐n‐butylphthalide preserves white matter integrity and alleviates cognitive impairment in mice with chronic cerebral hypoperfusion

“…Studies have demonstrated that NBP exerts multi‐target protective effects against ischemic stroke, including reducing oxidative stress, inhibiting inflammatory responses, alleviating neuronal apoptosis, ameliorating BBB damage, and increasing regional blood flow . Moreover, emerging evidence indicates that NBP also have beneficial effects on cognitive function of Alzheimer's Disease (AD) and vascular dementia, through regulating endoplasmic stress, reducing neuronal apoptosis, and glial reactivity …”

Application and prospects of butylphthalide for the treatment of neurologic diseases

“…[40] After 3 months of administration of dl-NBP, the levels of SYN and PSD-95 in SAMP 8 mice were significantly elevated. [41] In addition, the brain-derived neurotrophic factor (BNDF)/tropomyosin-related kinase B (TrkB) signaling pathway forms and consolidates memory by regulating synapse formation and plasticity. [41] BNDF and TrkB levels are significantly reduced in SAMP 8 mice, but dl-NBP treatment significantly increases both of the above in SAMP 8 mice.…”

“…[41] In addition, the brain-derived neurotrophic factor (BNDF)/tropomyosin-related kinase B (TrkB) signaling pathway forms and consolidates memory by regulating synapse formation and plasticity. [41] BNDF and TrkB levels are significantly reduced in SAMP 8 mice, but dl-NBP treatment significantly increases both of the above in SAMP 8 mice. [41] Long-term dl-NBP therapy may reduce cognitive decline in SAMP 8 mice by enhancing BDNF/TrkB signaling pathway through the regulation of structural synaptic plasticity.…”

“…[41] BNDF and TrkB levels are significantly reduced in SAMP 8 mice, but dl-NBP treatment significantly increases both of the above in SAMP 8 mice. [41] Long-term dl-NBP therapy may reduce cognitive decline in SAMP 8 mice by enhancing BDNF/TrkB signaling pathway through the regulation of structural synaptic plasticity. [41] It has also speculated that the distribution and expression of synaptic proteins SYN and PSD-95 may be regulated by the BDNF/TrkB signaling pathway.…”

Dl-3-n-butylphthalide inhibits phenytoin-induced neuronal apoptosis in rat hippocampus and cerebellum

“…Dl-3-n-butylphthalide (NBP) belongs to a new class of drugs that protect nerve cells and inhibit apoptosis and is used in the treatment of heart and cerebrovascular diseases (He et al, 2017;Lv et al, 2018). Whether NBP can inhibit PHT-induced apoptosis of nerve cells in the treatment of epilepsy is still unclear.…”