Bone marrow stromal cells promote neuroplasticity of cerebral ischemic rats via a phosphorylated CRMP2-mediated mechanism

Autor: Ting-Hua Wang, Xiang He, Qi-Qin Dan, Yue Hu, Jia Liu, Ling Jiang, Qiang Lv, Shu-Fen Wang
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Time Factors
Stromal cell
Synaptophysin
Ischemia
Down-Regulation
Mice
Transgenic
Nerve Tissue Proteins
Mesenchymal Stem Cell Transplantation
Rats
Sprague-Dawley
Mice
03 medical and health sciences
Behavioral Neuroscience
GAP-43 Protein
0302 clinical medicine
Antigens
CD
Internal medicine
Animals
Medicine
Gap-43 protein
GSK3B
Cells
Cultured
Neuronal Plasticity
biology
business.industry
Infarction
Middle Cerebral Artery
Mesenchymal Stem Cells
Evoked Potentials
Motor
medicine.disease
Rats
Disease Models
Animal
030104 developmental biology
Endocrinology
medicine.anatomical_structure
biology.protein
Intercellular Signaling Peptides and Proteins
Bone marrow
Collapsin response mediator protein family
business
Neuroscience
030217 neurology & neurosurgery
Signal Transduction
Neurotrophin
Zdroj: Behavioural Brain Research. 320:494-503
ISSN: 0166-4328
DOI: 10.1016/j.bbr.2016.10.027
Popis: Collapsin response mediator protein 2 (CRMP2), an important protein involved in axonal growth and the maintenance of neuronal membrane integrity, has proved to be altered in nervous system diseases. This study was aimed to investigate the role of CRMP2 in bone marrow stromal cells (BMSCs) treating rats with cerebral ischemia. BMSCs were isolated from shaft of the femurs, tibiae, and humeri and were intra-carotid administrated immediately after middle cerebral artery occlusion (MCAO). Modified Neurological Severity Scores (mNSS) was conducted at 3, 7, 14dpo and the electrophysiologic evaluation was evaluated at 14dpo. Then all rats were sacrificed and brain tissues were harvested for RT-PCR, Western blot and Immunohistochemistry analysis. We found BMSCs treatment significantly improved the neurobehavioral performance impaired by ischemic brain injury, accompanied with the notably increasing levels of Synaptophysin (SYP) and Growth associated protein 43 (GAP43). We also found the protein level of phosphorylated CRMP2 (p-CRMP2) and phosphorylation-mediated protein including Glycogen synthase kinase 3 Beta (GSK3β), Cyclin-dependent kinase 5 (CDK5) were dramatically downregulated in ischemic rats following BMSCs transplant. Furthermore, the GSK3β-mediated factors including neurotrophic and signaling factors were all significantly upregulated in BMSCs-treated group. On the basis of these findings, we suggest that the neuroplasticity effect of BMSCs on cerebral ischemia may be associated with the phosphorylated modulation of CRMP2.
Databáze: OpenAIRE
Externí odkaz: