Ghrelin Protects Spinal Cord Motoneurons Against Chronic Glutamate Excitotoxicity by Inhibiting Microglial Activation

• 영문명: Ghrelin Protects Spinal Cord Motoneurons Against Chronic Glutamate Excitotoxicity by Inhibiting Microglial Activation
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Sungyoub Lee Yumi Kim Endan Li Seungjoon Park
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제16권 제1호, 43~48쪽, 전체 6쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2012.01.01

영문 초록

Glutamate excitotoxicity is emerging as a contributor to degeneration of spinal cord motoneurons in amyotrophic lateral sclerosis (ALS). Recently, we have reported that ghrelin protects motoneurons against chronic glutamate excitotoxicity through the activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-3Ղ pathways. Previous studies suggest that activated microglia actively participate in the pathogenesis of ALS motoneuron degeneration. However, it is still unknown whether ghrelin exerts its protective effect on motoneurons via inhibition of microglial activation. In this study, we investigate organotypic spinal cord cultures (OSCCs) exposed to threohydroxyaspartate (THA), as a model of excitotoxic motoneuron degeneration, to determine if ghrelin prevents microglial activation. Exposure of OSCCs to THA for 3 weeks produced typical motoneuron death, and treatment of ghrelin significantly attenuated THA-induced motoneuron loss, as previously reported. Ghrelin prevented THA-induced microglial activation in the spinal cord and the expression of pro-inflammatory cytokines tumor necrosis factor-Ձ and interleukin-1Ղ. Our data indicate that ghrelin may act as a survival factor for motoneurons by functioning as a microglia- deactivating factor and suggest that ghrelin may have therapeutic potential for the treatment of ALS and other neurodegenerative disorders where inflammatory responses play a critical role.

키워드

Ghrelin Neuroinflammation Microglial activation Excitotoxicity Motoneuron