Limits...
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

GFP-labeled spinal cord motor neuron co-expressing NeuN.(A) GFP-labeled (green) ventral horn motor neuron (arrow) extending a single axon from the grey matter (GM) to the white matter (WM) (see arrowheads). (B-C) This GFP-labeled motor neuron co-expresses NeuN. (D-F) Higher magnification of the motor neuron in B-C. Scale bar (A-C) 150 μm, (D-F) 25 μm.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4514791&req=5

pone.0133903.g004: GFP-labeled spinal cord motor neuron co-expressing NeuN.(A) GFP-labeled (green) ventral horn motor neuron (arrow) extending a single axon from the grey matter (GM) to the white matter (WM) (see arrowheads). (B-C) This GFP-labeled motor neuron co-expresses NeuN. (D-F) Higher magnification of the motor neuron in B-C. Scale bar (A-C) 150 μm, (D-F) 25 μm.

Mentions: Purkinje cells are among the largest cells in the CNS and we hypothesize that it is only large cells that can harbor two nuclei and retain a stable functional identity post fusion. Other large neurons in the CNS are pyramidal cells in the cerebral cortex and motor neurons in the spinal cord. Therefore, we speculate that BMDCs might be able to fuse with motor neurons, forming stable heterokaryons. We analyzed different parts of the spinal cord at thoracic level 1–2 and lumbar level 3–4, particularly areas with prominent infiltration of immune cells (Fig 2A and 2B). Excitingly, we found several GFP-labeled spinal cord motor neurons, indicating that fusion between GFP-labeled BMDCs and motor neurons had taken place (Fig 3A–3F and S2–S4 Figs). These GFP-labeled motor neurons were primarily located in the ventral horns as well as the lateral column of the spinal cord; almost exclusively in or adjacent to major immune cell infiltration (S3 Fig). Some GFP-labeled motor neurons were binucleated (Fig 3A–3F and S4A–S4H Fig) and some were positive for the neuronal marker NeuN (Fig 4A–4F, S5A–S5H and S6A–S6D Figs). Sciatic nerve analysis of EAE affected mice also supported the fusion hypothesis between motor neurons and GFP-labeled BMDCs. Several GFP-labeled fibers were detected along the sciatic nerve (S7 Fig).


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)

GFP-labeled spinal cord motor neuron co-expressing NeuN.(A) GFP-labeled (green) ventral horn motor neuron (arrow) extending a single axon from the grey matter (GM) to the white matter (WM) (see arrowheads). (B-C) This GFP-labeled motor neuron co-expresses NeuN. (D-F) Higher magnification of the motor neuron in B-C. Scale bar (A-C) 150 μm, (D-F) 25 μm.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0133903.g004: GFP-labeled spinal cord motor neuron co-expressing NeuN.(A) GFP-labeled (green) ventral horn motor neuron (arrow) extending a single axon from the grey matter (GM) to the white matter (WM) (see arrowheads). (B-C) This GFP-labeled motor neuron co-expresses NeuN. (D-F) Higher magnification of the motor neuron in B-C. Scale bar (A-C) 150 μm, (D-F) 25 μm.
Mentions: Purkinje cells are among the largest cells in the CNS and we hypothesize that it is only large cells that can harbor two nuclei and retain a stable functional identity post fusion. Other large neurons in the CNS are pyramidal cells in the cerebral cortex and motor neurons in the spinal cord. Therefore, we speculate that BMDCs might be able to fuse with motor neurons, forming stable heterokaryons. We analyzed different parts of the spinal cord at thoracic level 1–2 and lumbar level 3–4, particularly areas with prominent infiltration of immune cells (Fig 2A and 2B). Excitingly, we found several GFP-labeled spinal cord motor neurons, indicating that fusion between GFP-labeled BMDCs and motor neurons had taken place (Fig 3A–3F and S2–S4 Figs). These GFP-labeled motor neurons were primarily located in the ventral horns as well as the lateral column of the spinal cord; almost exclusively in or adjacent to major immune cell infiltration (S3 Fig). Some GFP-labeled motor neurons were binucleated (Fig 3A–3F and S4A–S4H Fig) and some were positive for the neuronal marker NeuN (Fig 4A–4F, S5A–S5H and S6A–S6D Figs). Sciatic nerve analysis of EAE affected mice also supported the fusion hypothesis between motor neurons and GFP-labeled BMDCs. Several GFP-labeled fibers were detected along the sciatic nerve (S7 Fig).

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