Erinacine A attenuates glutamate transporter 1 downregulation and protects against ischemic brain injury

Pei Chien Hsu, Yi Jie Lan, Chin Chu Chen, Li Ya Lee, Wan Ping Chen, Yun Ching Wang, Yi Hsuan Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Maintaining glutamate homeostasis through astrocyte-enriched glutamate transporter 1 (GLT-1) is critical for neuronal survival, but it is often disrupted after brain injury. Hericium erinaceus (HE), an edible mushroom, was reported to be anti-inflammatory and neuroprotective against brain ischemia, but its effect on glutamate homeostasis was unknown. Here we investigated the neuroprotective effect of erinacine A (EA), an active component of HE, with special focus on the GLT-1 function in the in vitro and in vivo cerebral ischemia mouse models. By using oxygen-glucose deprivation (OGD) to challenge mouse glia-neuron (GN) mixed culture as the in vitro model, we found that EA treatment significantly improved neuronal/astroglial survival and attenuated OGD-induced proinflammatory NFκB and AKT signaling activations. Notably, EA attenuated OGD-induced GLT-1 downregulation, and a selective GLT-1 inhibitor WAY-213613 reversed these EA-mediated neuroprotection. EA also ameliorated glutamate excitotoxicity effectively. In a transient hypoxia-ischemia (tHI) brain injury mouse model, we examined an EA treatment strategy by performing a pre-tHI daily oral gavage of EA (oEA) for 7 days followed by a post-tHI intranasal injection of EA (nEA) for 3 days, and found that this treatment significantly protected sensorimotor cortex and improved the post-tHI forepaw grip strength. Western blotting results further revealed that EA treatment also preserved astrocyte-enriched glutamate and aspartate transporter (GLAST) as well as a GLT-1 function-associated potassium channel Kir4.1 in the cerebral cortex and striatum after tHI. These results suggest that EA is effective for preserving GLT-1 and glutamate clearance machinery to protect against excitotoxicity after ischemic brain injury.

Original languageEnglish
Article number120833
JournalLife Sciences
Volume306
DOIs
StatePublished - 1 Oct 2022

Keywords

  • Astrocytes
  • Erinacine A
  • Excitotoxicity
  • Glutamate transporter 1
  • Ischemic stroke
  • Kir4.1

Fingerprint

Dive into the research topics of 'Erinacine A attenuates glutamate transporter 1 downregulation and protects against ischemic brain injury'. Together they form a unique fingerprint.

Cite this