title: Improved regeneration after femoral nerve injury in mice lacking functional T- and B-lymphocytes.
abstract: The immune system plays important functional roles in regeneration after injury to the mammalian central and peripheral nervous systems. After damage to the peripheral nerve several types of immune cells, invade the nerve within hours after the injury. To gain insights into the contribution of T- and B-lymphocytes to recovery from injury we used the mouse femoral nerve injury paradigm. RAG2-/- mice lacking mature T- and B-lymphocytes due to deletion of the recombination activating gene 2 were subjected to resection and surgical reconstruction of the femoral nerve, with the wild-type mice of the same inbred genetic background serving as controls. According to single frame motion analyses, RAG2-/- mice showed better motor recovery in comparison to control mice at four and eight weeks after injury. Retrograde tracing of regrown/sprouted axons of spinal motoneurons showed increased numbers of correctly projecting motoneurons in the lumbar spinal cord of RAG2-/- mice compared with controls. Whereas there was no difference in the motoneuron soma size between genotypes, RAG2-/- mice displayed fewer cholinergic and inhibitory synaptic terminals around somata of spinal motoneurons both prior to and after injury, compared with wild-type mice. Extent of myelination of regrown axons in the motor branch of the femoral nerve measured as g-ratio was more extensive in RAG2-/- than in control mice eight weeks after injury. We conclude that activated T- and B-lymphocytes restrict motor recovery after femoral nerve injury, associated with the increased survival of motoneurons and improved remyelination.
authors: Center for Molecular Neurobiology Hamburg, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; Lebanese International University School of Arts & Sciences, P.O. Box: 146404 Mazraa, Beirut, Lebanon.
authors: Ali
authors: A
authors: Mehanna
authors: Center for Molecular Neurobiology Hamburg, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors: Emanuela
authors: E
authors: Szpotowicz
authors: Center for Molecular Neurobiology Hamburg, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Road, Shantou 515041, PR China. Electronic address: schachner@stu.edu.cn.
authors: Melitta
authors: M
authors: Schachner
authors: Center for Molecular Neurobiology Hamburg, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; Experimental Neurophysiology, University Hospital Cologne, Joseph-Stelzmann-Str. 9, 50931 Köln, Germany; German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. Electronic address: igor.jakovcevski@dzne.de.
authors: Igor
authors: I
authors: Jakovcevski
mesh_terms: D000578:Amidines; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D003911:Dextrans; D004195:Disease Models, Animal; D005260:Female; D020428:Femoral Neuropathy / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D009046:Motor Neurons / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D020127:Recovery of Function; D012235:Rhodamines; D013601:T-Lymphocytes / Q000502:physiology*; D013997:Time Factors; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
chemical_list: D000578:Amidines; D004268:DNA-Binding Proteins; D003911:Dextrans; C067661:Fluoro-Ruby; C499308:Rag2 protein, mouse; D012235:Rhodamines; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; C031455:diamidino compound 253-50; D002795:Choline O-Acetyltransferase
keywords: B- and T-lymphocytes; Excitatory and inhibitory synapses; Femoral nerve; Injury; Locomotion; Mouse; Myelination; Preferential motor reinnervation; Recombination activating gene 2