Local injection of BDNF producing mesenchymal stem cells increases neuronal survival and synaptic stability following ventral root avulsion.
The present study proposed to graft mesenchymal stem cells (MSCs), which continuously produce BDNF, into the spinal cord ventral horn, after ventral root avulsion. Neurotrophin expression was naturally achieved by culturing MSCs in an undifferentiated state for at least 10 weeks. Lewis rats were subjected to unilateral avulsion of lumbar ventral roots, receiving 3 x 10(5) cells injected through the lateral funiculus. Two weeks after surgery, the animals were sacrificed and neuronal survival, astroglial reaction and synaptic inputs within the motor nucleus analyzed. The results indicated that the MSCs treatment significantly rescued avulsed motoneurons. Such neuronal survival was related to in vivo mRNA up regulation as well as expression of BDNF and GDNF. Such increase was correlated to the preservation of synaptophysin- positive nerve terminals. Thus it was proposed that when maintained undifferentiated for a period of 10 weeks, MSCs may be used as a continuous source of BDNF, positively influencing neuronal survival and synaptic plasticity.
Rodrigues Hell
Rafaela Chitarra
RC
Department of Biochemistry and Immunology, ICB-UFMG, Brazil.
Silva Costa
Miriam Maria
MM
Goes
Alfredo Miranda
AM
Oliveira
Alexandre L R
AL
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002454:Cell Differentiation; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009046:Motor Neurons / Q000502:physiology*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D011843:Radiculopathy / Q000503:physiopathology* / Q000628:therapy; D051381:Rats; D013126:Spinal Nerve Roots / Q000503:physiopathology; D013569:Synapses / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D016708:Synaptophysin