title: Cell Fusion along the Anterior-Posterior Neuroaxis in Mice with Experimental Autoimmune Encephalomyelitis.
abstract: BACKGROUND
  It is well documented that bone marrow-derived cells can fuse with a diverse range of cells, including brain cells, under normal or pathological conditions. Inflammation leads to robust fusion of bone marrow-derived cells with Purkinje cells and the formation of binucleate heterokaryons in the cerebellum. Heterokaryons form through the fusion of two developmentally differential cells and as a result contain two distinct nuclei without subsequent nuclear or chromosome loss.
  
  
  OBJECTIVE
  In the brain, fusion of bone marrow-derived cells appears to be restricted to the complex and large Purkinje cells, raising the question whether the size of the recipient cell is important for cell fusion in the central nervous system. Purkinje cells are among the largest neurons in the central nervous system and accordingly can harbor two nuclei.
  
  
  RESULTS
  Using a well-characterized model for heterokaryon formation in the cerebellum (experimental autoimmune encephalomyelitis - a mouse model of multiple sclerosis), we report for the first time that green fluorescent protein-labeled bone marrow-derived cells can fuse and form heterokaryons with spinal cord motor neurons. These spinal cord heterokaryons are predominantly located in or adjacent to an active or previously active inflammation site, demonstrating that inflammation and infiltration of immune cells are key for cell fusion in the central nervous system. While some motor neurons were found to contain two nuclei, co-expressing green fluorescent protein and the neuronal marker, neuron-specific nuclear protein, a number of small interneurons also co-expressed green fluorescent protein and the neuronal marker, neuron-specific nuclear protein. These small heterokaryons were scattered in the gray matter of the spinal cord.
  
  
  CONCLUSIONS
  This novel finding expands the repertoire of neurons that can form heterokaryons with bone marrow-derived cells in the central nervous system, albeit in low numbers, possibly leading to a novel therapy for spinal cord motor neurons or other neurons that are compromised in the central nervous system.
authors.affiliation: Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sreenivasa R
authors.initials: SR
authors.lastname: Sankavaram
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mikael A
authors.initials: MA
authors.lastname: Svensson
authors.affiliation: Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.affiliation: Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lou
authors.initials: L
authors.lastname: Brundin
authors.affiliation: Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Public Dental Service at Gällö, Jämtland Härjedalen County Council, Gällö, Sweden.
authors.forename: Clas B
authors.initials: CB
authors.lastname: Johansson
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D002490:Central Nervous System / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D015726:Giant Cells / Q000473:pathology*; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D009103:Multiple Sclerosis / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins