本日は、軸索誘導因子のSLIT-ROBO1の機能について学びました。本日はニューロサイエンス学位プログラム2月期入試の結果発表がありました。ジャーナルクラブの後、Li Jininminが第5回解剖グループ研究会発表の予行練習を行いました。3月には大学院前期課程修了が控えており、感性認知脳科学専攻の学生として最後の研究発表に臨みます。セミナー後にLiからコロナウィルスへの注意喚起がありました。注意して学内業務にあたりたいと思います。

Neuropharmacology

Volume 158, 1 November 2019, 107727

Recombinant Slit2 attenuates neuronal apoptosis via the Robo1-srGAP1 pathway in a rat model of neonatal HIE

HarpreetKaur^aNingboXu^aDesislavaMetDoycheva^aJayMalaguit^aJipingTang^aJohn H.Zhang^aba

Department of Physiology and Pharmacology, Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, 92354, USA^bDepartment of Anesthesiology, Neurosurgery and Neurology, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA

Highlights

• Slit2 and Robo-1 expression is increased after neonatal brain injury.

• Recombinant Slit2 has a protective effect on brain infarction and neurobehavior after HI.

• Recombinant Slit2 attenuated apoptosis after HI.

• Recombinant Slit2 attenuated apoptosis via Robo1-srGap1 pathway.

Abstract

Apoptosis following hypoxic-ischemic injury to the brain plays a major role in neuronal cell death. The neonatal brain is more susceptible to injury as the cortical neurons are immature and there are lower levels of antioxidants. Slit2, an extracellular matrix protein, has been shown to be neuroprotective in various models of neurological diseases. However, there is no information about the role of Slit2 in neonatal hypoxia-ischemia. In this study, we evaluated the effect of Slit2 and its receptor Robo1 in a rat model with neonatal HIE. 10-day old rat pups were used to create the neonatal HIE model. The right common carotid artery was ligated followed by 2.5 h of hypoxia. Recombinant Slit2 was administered intranasally 1 h post HI, recombinant Robo1 was used as a decoy receptor and administered intranasally 1h before HI and srGAP1-siRNA was administered intracerebroventricularly 24 h before HI. Brain infarct area measurement, short-term and long-term neurological function tests, Western blot, immunofluorescence staining, Fluoro-Jade C staining, Nissl staining and TUNEL staining were the assessments done following drug administration. Recombinant Slit2 administration reduced neuronal apoptosis and neurological deficits after neonatal HIE which were reversed by co-administration of recombinant Robo1 and srGAP1-siRNA administration. Recombinant Slit2 showed improved outcomes possibly via the robo1-srGAP1 pathway which mediated the inhibition of RhoA. In this study, the results suggest that Slit2 may help in attenuation of apoptosis and could be a therapeutic agent for treatment of neonatal hypoxic ischemic encephalopathy.