Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (10): 2285-2290.doi: 10.4103/1673-5374.369124

Previous Articles     Next Articles

Astrocyte-neuron communication mediated by the Notch signaling pathway: focusing on glutamate transport and synaptic plasticity

Ke-Xin Li, Meng Lu, Meng-Xu Cui, Xiao-Ming Wang*, Yang Zheng*   

  1. Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
  • Online:2023-10-15 Published:2023-03-29
  • Contact: Yang Zheng, MD, zhengyang19871114@163.com; Xiao-Ming Wang, MD, wangxm024@163.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81871408 and 81271631 (to XMW), National Science Foundation for Young Scientists of China, No. 81801658 (to YZ), Outstanding Scientific Fund of Shengjing Hospital, No. 201402 (to XMW), and 345 Talent Support Project of Shengjing Hospital, No. 30B (to YZ).

PDF

132

Abstract: Maintaining glutamate homeostasis after hypoxic ischemia is important for synaptic function and neural cell activity, and regulation of glutamate transport between astrocyte and neuron is one of the important modalities for reducing glutamate accumulation. However, further research is needed to investigate the dynamic changes in and molecular mechanisms of glutamate transport and the effects of glutamate transport on synapses. The aim of this study was to investigate the regulatory mechanisms underlying Notch pathway mediation of glutamate transport and synaptic plasticity. In this study, Yorkshire neonatal pigs (male, age 3 days, weight 1.0–1.5 kg, n = 48) were randomly divided into control (sham surgery group) and five hypoxic ischemia subgroups, according to different recovery time, which were then further subdivided into subgroups treated with dimethyl sulfoxide or a Notch pathway inhibitor (N-[N-(3, 5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester). Once the model was established, immunohistochemistry, immunofluorescence staining, and western blot analyses of Notch pathway-related proteins, synaptophysin, and glutamate transporter were performed. Moreover, synapse microstructure was observed by transmission electron microscopy. At the early stage (6–12 hours after hypoxic ischemia) of hypoxic ischemic injury, expression of glutamate transporter excitatory amino acid transporter-2 and synaptophysin was downregulated, the number of synaptic vesicles was reduced, and synaptic swelling was observed; at 12–24 hours after hypoxic ischemia, the Notch pathway was activated, excitatory amino acid transporter-2 and synaptophysin expression was increased, and the number of synaptic vesicles was slightly increased. Excitatory amino acid transporter-2 and synaptophysin expression decreased after treatment with the Notch pathway inhibitor. This suggests that glutamate transport in astrocytes-neurons after hypoxic ischemic injury is regulated by the Notch pathway and affects vesicle release and synaptic plasticity through the expression of synaptophysin.

Key words: astrocyte, astrocyte-neuron communication, glutamate, glutamate transporter, hypoxic-ischemic injury, magnetic resonance spectroscopy, neonate, Notch signaling pathway, plasticity, synapse