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Cell Fusion along the Anterior-Posterior Neuroaxis in Mice with Experimental Autoimmune Encephalomyelitis.

Sankavaram SR, Svensson MA, Olsson T, Brundin L, Johansson CB - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

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.

Aim: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Quantification and distribution of heterokaryons in EAE affected and Control spinal cord.(A) While there was a wide spread in the number of heterokaryons between individual EAE affected mice (n = 5; 20.0 ± 6.7), depending on the severity of inflammation, there were significantly more heterokaryons (p = 0.0358, Mann-Whitney-Wilcoxon test) in EAE affected mice than Control (n = 3; 0.3 ± 0.3) mice. (B) Schematic representation of the distribution of heterokaryons in 20 sections of EAE spinal cord. Each symbol represents one experimental animal, and the symbol size represents heterokaryon size (small symbol: <20 μm, large: >20 μm).
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pone.0133903.g005: Quantification and distribution of heterokaryons in EAE affected and Control spinal cord.(A) While there was a wide spread in the number of heterokaryons between individual EAE affected mice (n = 5; 20.0 ± 6.7), depending on the severity of inflammation, there were significantly more heterokaryons (p = 0.0358, Mann-Whitney-Wilcoxon test) in EAE affected mice than Control (n = 3; 0.3 ± 0.3) mice. (B) Schematic representation of the distribution of heterokaryons in 20 sections of EAE spinal cord. Each symbol represents one experimental animal, and the symbol size represents heterokaryon size (small symbol: <20 μm, large: >20 μm).

Mentions: The number of heterokaryons in EAE affected mice (n = 5; 20.0 ± 6.7) was higher than in non-immunized control animals (n = 3; 0.3 ± 0.3), (p = 0.0358, Mann-Whitney-Wilcoxon test, Fig 5A). We observed both large GFP-labeled motor neurons and small GFP-labeled interneurons scattered around the spinal cord (Fig 5B). Some of these GFP-labeled interneurons also expressed, NeuN (Fig 6A–6C, S8A–S8C, S9A and S9C and S10A–S10C Figs). The GFP-labeled motor neurons as well as the GFP-labeled interneurons contributed to the local neuronal circuitry (Fig 6D).


Cell Fusion along the Anterior-Posterior Neuroaxis in Mice with Experimental Autoimmune Encephalomyelitis.

Sankavaram SR, Svensson MA, Olsson T, Brundin L, Johansson CB - PLoS ONE (2015)

Quantification and distribution of heterokaryons in EAE affected and Control spinal cord.(A) While there was a wide spread in the number of heterokaryons between individual EAE affected mice (n = 5; 20.0 ± 6.7), depending on the severity of inflammation, there were significantly more heterokaryons (p = 0.0358, Mann-Whitney-Wilcoxon test) in EAE affected mice than Control (n = 3; 0.3 ± 0.3) mice. (B) Schematic representation of the distribution of heterokaryons in 20 sections of EAE spinal cord. Each symbol represents one experimental animal, and the symbol size represents heterokaryon size (small symbol: <20 μm, large: >20 μm).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4514791&req=5

pone.0133903.g005: Quantification and distribution of heterokaryons in EAE affected and Control spinal cord.(A) While there was a wide spread in the number of heterokaryons between individual EAE affected mice (n = 5; 20.0 ± 6.7), depending on the severity of inflammation, there were significantly more heterokaryons (p = 0.0358, Mann-Whitney-Wilcoxon test) in EAE affected mice than Control (n = 3; 0.3 ± 0.3) mice. (B) Schematic representation of the distribution of heterokaryons in 20 sections of EAE spinal cord. Each symbol represents one experimental animal, and the symbol size represents heterokaryon size (small symbol: <20 μm, large: >20 μm).
Mentions: The number of heterokaryons in EAE affected mice (n = 5; 20.0 ± 6.7) was higher than in non-immunized control animals (n = 3; 0.3 ± 0.3), (p = 0.0358, Mann-Whitney-Wilcoxon test, Fig 5A). We observed both large GFP-labeled motor neurons and small GFP-labeled interneurons scattered around the spinal cord (Fig 5B). Some of these GFP-labeled interneurons also expressed, NeuN (Fig 6A–6C, S8A–S8C, S9A and S9C and S10A–S10C Figs). The GFP-labeled motor neurons as well as the GFP-labeled interneurons contributed to the local neuronal circuitry (Fig 6D).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

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.

Aim: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus