ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.

Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions. In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. ATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke. © 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.

Citation

Jonathan Z Pan, Zhanqiang Wang, Wei Sun, Peipei Pan, Wei Li, Yongtao Sun, Shoulin Chen, Amity Lin, Wulin Tan, Liangliang He, Jacob Greene, Virginia Yao, Lijun An, Rich Liang, Qifeng Li, Jessica Yu, Lingyi Zhang, Nikolaos Kyritsis, Xuan Duong Fernandez, Sara Moncivais, Esmeralda Mendoza, Pamela Fung, Gongming Wang, Xinhuan Niu, Qihang Du, Zhaoyang Xiao, Yuwen Chang, Peiyuan Lv, J Russell Huie, Abel Torres-Espin, Adam R Ferguson, Debra D Hemmerle, Jason F Talbott, Philip R Weinstein, Lisa U Pascual, Vineeta Singh, Anthony M DiGiorgio, Rajiv Saigal, William D Whetstone, Geoffrey T Manley, Sanjay S Dhall, Jacqueline C Bresnahan, Mervyn Maze, Xiangning Jiang, Neel S Singhal, Michael S Beattie, Hua Su, Zhonghui Guan. ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke. Clinical and translational medicine. 2024 Apr;14(4):e1650

Mesh Tags

Substances

PMID: 38649772

search → result