CX3CR1 deficiency aggravates brain white matter injury and affects expression of the CD36/15LO/NR4A1 signal
Wenzhu Wang1, Jingbo Wang2, Qing Tang1
1Department of Integrated Traditional and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Objective:
To study the effects of CX3CR1 on white matter injury, neurofunction, recognition, and expression of the CD36/15LO/NR4A1 signal in mice with traumatic brain injury (TBI).
Methods:
CX3CR1GFP/GFP, CX3CR1GFP/+ and C57BL/6 male mice were randomly divided into 3 groups. We used a controlled cortical impact (CCI) to establish a TBI model and T2wt MRI to detect the TBI lesion. FA and DTI allowed for quantitative evaluation of the structural integrity of white matter tracts. Several behavior tests were used to investigate nerve function; a computer-based tracing system was used to trace and analyze dendrites and cell bodies of microglia and astrocytes in the peri-lesional brain areas. We also used RT-PCR and western blot to detect the effect of CX3CL1/CX3CR1 axis on CD36/15LO/NR4A1 signal.
Results:
The fractional anisotropy (FA) at the corpus callosum area of brain was decreased at 3 days post TBI, the average lesion volume CX3CR1GFP/GFP group was increased, and the neurologic deficit scores of mice of Cx3Cr1GFP/+ and wild-type groups were significantly increased compared to Cx3Cr1GFP/GFP group mice. In the Corner turn test, TBI induced impairments in forelimb function that were more severe than Cx3Cr11GFP/+ and wild-type TBI mice. We operated the Y-maze at 3 days post-TBI and the NOR test at 28 days after TBI. There was a significant TBI effect induced in decreased percentage entries into the novel arm in Cx3Cr1GFP/+ and wild-type TBI mice, compared with Cx3Cr1GFP/GFP; Cx3Cr1GFP/+. Wild-type mice showed decreased exploration time in new objects compared with Cx3Cr1GFP/GFP. Those two behavior tests demonstrated that Cx3Cr1 knock-out increased the damage caused by TBI to memory. In the tail suspension and force swimming tests, there was no significant difference between those three groups. CD36 increased in Cx3Cr1GFP/GFP compared with the other three groups at 3 days after TBI. TBI inhibited the expression of NR4A1 at 3 d after damage. Cx3Cr1 deficiency can induce high expression of 15LO, this was unaffected by TBI.
Conclusion:
CX3CR1 deletion can enhance white matter injury. It increased the expression of CD36 and 15LO and increased expression of NR4A1. The lack of CX3CR1 can affect the recovery of nerve function.
Insights
CX3CR1 deletion exacerbates white matter injury and cognitive deficits after traumatic brain injury (TBI) in mice. This deficiency increases CD36 and 15LO expression, impairing neurological recovery.
Area of Science:
- Neuroscience
- Immunology
- Traumatic Brain Injury Research
Background:
- Traumatic brain injury (TBI) can lead to significant white matter damage and long-term neurological deficits.
- The CX3CR1 receptor and its ligand CX3CL1 play roles in neuroinflammation and microglial function, potentially influencing TBI outcomes.
Purpose of the Study:
- To investigate the role of CX3CR1 in white matter injury, neurofunction, and recognition following TBI.
- To examine the impact of CX3CR1 deficiency on the expression of the CD36/15LO/NR4A1 signaling pathway post-TBI.
Main Methods:
- A controlled cortical impact (CCI) model of TBI was used in CX3CR1-deficient (CX3CR1GFP/GFP), heterozygous (CX3CR1GFP/+), and wild-type mice.
- White matter integrity was assessed using fractional anisotropy (FA) and diffusion tensor imaging (DTI).
- Neurobehavioral tests evaluated cognitive and motor functions, while RT-PCR and Western blot analyzed specific gene and protein expressions.
Main Results:
- CX3CR1 deficiency worsened white matter damage, evidenced by decreased FA and increased lesion volume.
- Mice lacking CX3CR1 exhibited more severe impairments in forelimb function, spatial recognition, and memory compared to controls.
- CX3CR1 deficiency led to increased expression of CD36 and 15LO, and altered NR4A1 expression post-TBI.
Conclusions:
- CX3CR1 deletion significantly enhances white matter injury and neurological deficits after TBI.
- The absence of CX3CR1 impacts the recovery of nerve function and alters key molecular signaling pathways involved in brain injury.
More Related Videos
08:47Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016
04:43Author Spotlight: Insights and Innovations in Gene Expression Manipulation Techniques for Choroid Plexus Research
Published on: June 16, 2023