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ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.
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- Author(s): Pan JZ;Pan JZ; Wang Z; Wang Z; Wang Z; Wang Z; Sun W; Sun W; Sun W; Pan P; Pan P; Pan P; Li W; Li W; Li W; Sun Y; Sun Y; Sun Y; Chen S; Chen S; Chen S; Lin A; Lin A; Tan W; Tan W; Tan W; He L; He L; He L; Greene J; Greene J; Yao V; Yao V; An L; An L; An L; Liang R; Liang R; Liang R; Li Q; Li Q; Li Q; Li Q; Yu J; Yu J; Zhang L; Zhang L; Kyritsis N; Kyritsis N; Kyritsis N; Fernandez XD; Fernandez XD; Fernandez XD; Moncivais S; Moncivais S; Moncivais S; Mendoza E; Mendoza E; Mendoza E; Fung P; Fung P; Wang G; Wang G; Wang G; Niu X; Niu X; Niu X; Du Q; Du Q; Du Q; Xiao Z; Xiao Z; Xiao Z; Chang Y; Chang Y; Lv P; Lv P; Lv P; Huie JR; Huie JR; Huie JR; Torres-Espin A; Torres-Espin A; Torres-Espin A; Ferguson AR; Ferguson AR; Ferguson AR; Hemmerle DD; Hemmerle DD; Hemmerle DD; Talbott JF; Talbott JF; Weinstein PR; Weinstein PR; Weinstein PR; Pascual LU; Pascual LU; Singh V; Singh V; DiGiorgio AM; DiGiorgio AM; DiGiorgio AM; Saigal R; Saigal R; Saigal R; Whetstone WD; Whetstone WD; Manley GT; Manley GT; Manley GT; Dhall SS; Dhall SS; Bresnahan JC; Bresnahan JC; Bresnahan JC; Maze M; Maze M; Maze M; Jiang X; Jiang X; Singhal NS; Singhal NS; Beattie MS; Beattie MS; Beattie MS; Su H; Su H; Su H; Guan Z; Guan Z
- Source:
Clinical and translational medicine [Clin Transl Med] 2024 Apr; Vol. 14 (4), pp. e1650.- Publication Type:
Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural- Language:
English - Source:
- Additional Information
- Source: Publisher: Wiley Country of Publication: United States NLM ID: 101597971 Publication Model: Print Cited Medium: Internet ISSN: 2001-1326 (Electronic) Linking ISSN: 20011326 NLM ISO Abbreviation: Clin Transl Med Subsets: MEDLINE
- Publication Information: Publication: 2020- : [Hoboken, NJ] : Wiley
Original Publication: Heidelberg : Springer-Verlag - Subject Terms: Activating Transcription Factor 3*/metabolism ; Activating Transcription Factor 3*/genetics ; Biomarkers*/metabolism ; Biomarkers*/blood ; Ischemic Stroke*/metabolism ; Ischemic Stroke*/genetics ; Ischemic Stroke*/blood ; Neurons*/metabolism ; Spinal Cord Injuries*/metabolism ; Spinal Cord Injuries*/genetics ; Spinal Cord Injuries*/complications; Animals ; Female ; Humans ; Male ; Mice ; Disease Models, Animal ; Mice, Knockout
- Abstract: Background: 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.
Methods: 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.
Results: 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.
Conclusions: ATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties.
Highlights: 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.
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- Contributed Indexing: Keywords: activating transcription factor 3 (ATF3); biomarker; neuronal injury; neuroprotection; spinal cord injury; stroke
- Accession Number: 0 (Activating Transcription Factor 3)
0 (ATF3 protein, human)
0 (Atf3 protein, mouse)
0 (Biomarkers) - Publication Date: Date Created: 20240422 Date Completed: 20240429 Latest Revision: 20240503
- Publication Date: 20240504
- Accession Number: PMC11035380
- Accession Number: 10.1002/ctm2.1650
- Accession Number: 38649772
- Source:
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