DL-3-n-butylphthalide enhances synaptic plasticity in mouse model of brain impairments

Qian Ding; Qian Yu; Lei Tao; Yifei Guo; Juan Zhao; Jun Yu

doi:10.37175/stemedicine.v3i1.113

Qian Ding Department of Anesthesiology, Xi’an International Medical Center Hospital, Northwest University, Xi’an, Shaanxi, China
Qian Yu Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, China
Lei Tao Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, China
Yifei Guo Clinical Experimental Center, Xi’an International Medical Center Hospital, Northwest University, Xi’an, Shaanxi, China
Juan Zhao Department of Anesthesiology, Xi’an International Medical Center Hospital, Northwest University, Xi’an, Shaanxi, China
Jun Yu Clinical Experimental Center, Xi’an International Medical Center Hospital, Northwest University, Xi’an, Shaanxi, China

DOI: https://doi.org/10.37175/stemedicine.v3i1.113

Keywords: synaptic plasticity, L-3-n-butylphthalide, glutamate, Alzheimer’s disease, learning and memory ability

Abstract

Synaptic impairment results in cognitive dysfunction of Alzheimer’s disease (AD). As a plant extract, it is found that DL-3-n-butylphthalide (L-NBP) rescues abnormal cognitive behaviors in AD animals. However, the regulatory effects of L-NBP on synaptic plasticity remains unclear. APP/PS1 mice at 12 months old received oral L-NBP treatment for 12 weeks. A water maze test assessed cognitive performances. In vitro patch-clamp recordings and in vivo field potential recordings were performed to evaluate synaptic plasticity. The protein expression of AMPA receptor subunits (GluR1 and GluR2) and NMDA receptor subunits (NR1, NR2A, and NR2B) was examined by Western blot. In addition, glutaminase activity and glutamate level in the hippocampus were measured by colorimetry to evaluate presynaptic glutamate release. L-NBP treatment could significantly improve learning and memory ability, upregulate NR2A and NR2B protein expressions, increase glutaminase activity and glutamate level in the hippocampus, and attenuate synaptic impairment transmission in the AD mice. L-NPB plays a beneficial role in AD mice by regulating NMDA receptor subunits’ expression and regulating presynaptic glutamate release.

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