Unbiased transcriptomic analyses reveal distinct effects of immune deficiency in CNS function with and without injury

Autor: Qiao Yan, Haotian Li, Yanan Geng, Sheng Lin, Wei Xu, Liming Cheng, Juehua Yu, Bo Jing, Chong Zhang, Quan Lin, Weihong Ge, Dandan Luo, Lei Chen, Changhong Zheng, Xiao Hu, Rongrong Zhu, Chia Ming Lee, Kun Jiang, Zhen Wang, Liqiang Zhou, Jing Yu, Keqiang Ye, Chen Li, Zhourui Wu, Yi Eve Sun, Xinpei Gao, Xingfei Zhu
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
lcsh:Animal biochemistry
neurotransmision
Morris water navigation task
Mice
SCID
Neurodegenerative
Inbred C57BL
Biochemistry
Mice
0302 clinical medicine
Injury - Trauma - (Head and Spine)
Drug Discovery
Spinal Cord Injury
Spinal cord injury
transcriptomic analysis
lcsh:Cytology
Neurodegeneration
3. Good health
medicine.anatomical_structure
030220 oncology & carcinogenesis
Neurological
medicine.symptom
Stem cell
Biotechnology
Research Article
spinal cord injury repair
Central nervous system
Inflammation
Blood–brain barrier
SCID
03 medical and health sciences
Immune system
medicine
Genetics
Animals
lcsh:QH573-671
lcsh:QP501-801
Spinal Cord Injuries
business.industry
Gene Expression Profiling
Neurosciences
Cell Biology
Recovery of Function
immune deficiency
medicine.disease
Mice
Inbred C57BL
030104 developmental biology
Immunology
Injury (total) Accidents/Adverse Effects
Biochemistry and Cell Biology
business
Zdroj: Protein & Cell
Protein & cell, vol 10, iss 8
Protein & Cell, Vol 10, Iss 8, Pp 566-582 (2018)
ISSN: 1674-8018
1674-800X
Popis: The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation. Electronic supplementary material The online version of this article (10.1007/s13238-018-0559-y) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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