Focal Transplantation of Aberrant Glial Cells Carrying the SOD1G93A Mutation into Rat Spinal Cord Induces Extensive Gliosis.

Abstract

OBJECTIVE:

We aimed to determine the potential of aberrant glial cells (AbAs) isolated from the spinal cord of adult SOD1G93A symptomatic rats to induce gliosis and neuronal damage following focal transplantation into the lumbar spinal cord of wild-type rats.

METHODS:

AbAs were obtained from the spinal cords of SOD1G93A symptomatic rats. One hundred thousand cells were injected using a glass micropipette into the lumbar spinal cords (L3-L5) of syngeneic wild-type adult rats. Equal volumes of culture medium or wild-type neonatal microglia were used as controls. Seven days after transplantation, immunohistochemistry analysis was carried out using astrocytic and microglia cell markers. Transplanted SOD1G93A AbAs were recognized by specific antibodies to human SOD1 (hSOD1) or misfolded human SOD1.

RESULTS:

Seven days after transplantation, AbAs were mainly detected in the medial region of the lumbar ventral horn as a well-limited cell cluster formed at the site of injection by their immunoreactivity to either misfolded SOD1 or normally folded hSOD1. Compared with controls, transplanted AbAs were surrounded by marked microgliosis and reactive astrocytes. Marked microgliosis was observed to extend bilaterally up to the cervical cord. Motor neurons close to AbA transplants were surrounded by activated glial cells and displayed ubiquitin aggregation.

CONCLUSIONS:

AbAs bearing mutant SOD1G93A have the potential to induce neuroinflammation along the spinal cord and incipient damage to the motor neurons. The emergence of AbAs during amyotrophic lateral sclerosis pathogenesis may therefore be a mechanism to boost neuroinflammation and spread motor neuron damage along the neuroaxis.

• Authors: Sofía Ibarburu, Emiliano Trias, Natalia Lago, Hugo Peluffo, Romina Barreto-Núñez, Valentina Varela, Joseph S Beckman, Luis Barbeito
• Journal: Neuroimmunomodulation (Neuroimmunomodulation) Vol. 24 Issue 3 Pg. 143-153 ( 2017) ISSN: 1423-0216 [Electronic] Switzerland
• PMID: 29131016 (Publication Type: Journal Article)
• Copyright: © 2017 S. Karger AG, Basel.

Chemical References

• Aif1 protein, rat
• Calcium-Binding Proteins
• Glial Fibrillary Acidic Protein
• Microfilament Proteins
• Ubiquitin
• SOD1 G93A protein
• Superoxide Dismutase

Topics

• Animals
• Calcium-Binding Proteins (metabolism)
• Functional Laterality
• Glial Fibrillary Acidic Protein (metabolism)
• Gliosis (etiology, genetics)
• Male
• Microfilament Proteins (metabolism)
• Motor Neurons (pathology)
• Mutation (genetics)
• Neuroglia (metabolism, transplantation)
• Rats
• Rats, Transgenic
• Spinal Cord (pathology)
• Superoxide Dismutase (genetics, metabolism)
• Ubiquitin (metabolism)