Dissecting Genetic Mechanisms of Differential Locomotion, Depression, and Allodynia after Spinal Cord Injury in Three Mouse Strains
Wendy W. Yang,
Jessica J. Matyas,
Yun Li,
Hangnoh Lee,
Zhuofan Lei,
Cynthia L. Renn,
Alan I. Faden,
Susan G. Dorsey,
Junfang Wu
Affiliations
Wendy W. Yang
Department of Anesthesiology and Shock, Trauma and Anesthesiology Research Center (STAR), University of Maryland School of Medicine, Baltimore, MD 21201, USA
Jessica J. Matyas
Department of Anesthesiology and Shock, Trauma and Anesthesiology Research Center (STAR), University of Maryland School of Medicine, Baltimore, MD 21201, USA
Yun Li
Department of Anesthesiology and Shock, Trauma and Anesthesiology Research Center (STAR), University of Maryland School of Medicine, Baltimore, MD 21201, USA
Hangnoh Lee
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Zhuofan Lei
Department of Anesthesiology and Shock, Trauma and Anesthesiology Research Center (STAR), University of Maryland School of Medicine, Baltimore, MD 21201, USA
Cynthia L. Renn
Department of Pain and Translational Symptom Science, University of Maryland School of Nursing, Baltimore, MD 21201, USA
Alan I. Faden
Department of Anesthesiology and Shock, Trauma and Anesthesiology Research Center (STAR), University of Maryland School of Medicine, Baltimore, MD 21201, USA
Susan G. Dorsey
Department of Pain and Translational Symptom Science, University of Maryland School of Nursing, Baltimore, MD 21201, USA
Junfang Wu
Department of Anesthesiology and Shock, Trauma and Anesthesiology Research Center (STAR), University of Maryland School of Medicine, Baltimore, MD 21201, USA
Strain differences have been reported for motor behaviors, and only a subset of spinal cord injury (SCI) patients develop neuropathic pain, implicating genetic or genomic contribution to this condition. Here, we evaluated neuropsychiatric behaviors in A/J, BALB/c, and C57BL/6 male mice and tested genetic or genomic alterations following SCI. A/J and BALB/c naive mice showed significantly less locomotor activity and greater anxiety-like behavior than C57BL/6 mice. Although SCI elicited locomotor dysfunction, C57BL/6 and A/J mice showed the best and the worst post-traumatic recovery, respectively. Mild (m)-SCI mice showed deficits in gait dynamics. All moderate/severe SCI mice exhibited similar degrees of anxiety/depression. mSCI in BALB/c and A/J mice resulted in depression, whereas C57BL/6 mice did not exhibit depression. mSCI mice had significantly lower mechanical thresholds than their controls, indicating high cutaneous hypersensitivity. C57BL/6, but not A/J and BLAB/c mice, showed significantly lower heat thresholds than their controls. C57BL/6 mice exhibited spontaneous pain. RNAseq showed that genes in immune responses and wound healing were upregulated, although A/J mice showed the largest increase. The cell cycle and the truncated isoform of trkB genes were robustly elevated in SCI mice. Thus, different genomics are associated with post-traumatic recovery, underscoring the likely importance of genetic factors in SCI.
