Laminin degradation by matrix metalloproteinase 9 promotes ketamine‐induced neuronal apoptosis in the early developing rat retina. (20th June 2020)

• Record Type: Journal Article
• Authors: Wu, Lei; Zhang, Kan; Sun, Liping; Bai, Jie; Zhang, Mazhong; Zheng, Jijian
• Is Part Of: CNS neuroscience & therapeutics. Volume 26:Number 10(2020)
• Page Start: 1058
• Page End: 1068
• Publication Date: 2020-06-20
• Subjects: apoptosis -- ketamine -- laminin -- matrix metalloproteinase -- Zn2+; Neuropharmacology -- Periodicals; Central nervous system -- Diseases -- Effect of drugs on -- Periodicals; 612.8
• DOI: 10.1111/cns.13428
• Languages: English
• ISSNs: 1755-5930

Abstract

Abstract: Aims: During early development, laminin degradation contributes to the death of neurons. This study aims to investigate the role and regulation of laminin in ketamine‐induced apoptosis. Methods: We performed terminal deoxynucleotidyl transferase biotin‐dUTP nick end labeling (TUNEL) and immunohistochemical assays to investigate the roles of the non‐integrin laminin receptor, matrix metalloproteinase 9 (MMP9) in ketamine‐induced neuronal apoptosis. In situ zymography, Western blot, and immunofluorescence were used to explore the relationships between laminin, MMP9 activity, and Zn 2+ . Experiments were performed using whole‐mount retinas dissected from Sprague Dawley rats. Results: The TUNEL and immunohistochemical assays indicated that ketamine‐induced neuronal apoptosis in early developing rat retina. Blockade of non‐integrin laminin receptor promoted ketamine‐induced apoptosis, while non‐integrin laminin receptor activation attenuated ketamine‐induced apoptosis. Ketamine‐induced laminin degradation, possibly by enhancing the activity of MMP9. MMP9 inhibition reduced ketamine‐induced apoptosis by reducing laminin degradation. Downregulation of Zn 2+ attenuated the increased MMP9 activity, laminin degradation caused by ketamine and significantly reduced ketamine‐induced neuronal apoptosis. Conclusion: Laminin degradation by MMP9 promoted ketamine‐induced neuronal apoptosis in early developing rat retina. The non‐integrin laminin receptor may be a pathway involved in ketamine‐induced apoptosis. Zn 2+ downregulation may play a protective role against ketamine‐induced neuronal apoptosis through inhibiting MMP9 activity.