Elevated levels of IFNγ and LIGHT in the spinal cord of patients with sporadic amyotrophic lateral sclerosis.
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a paralytic and fatal neurodegenerative disorder caused by the gradual loss of both upper and lower motoneurons. There is compelling evidence from ALS experimental models that neuroinflammation actively contributes to motoneuron damage. We recently proposed that interferon gamma (IFNγ), a potent proinflammatory cytokine, induces motoneuron death by eliciting the activation of the lymphotoxin beta receptor (LT-βR) through its ligand LIGHT. Here, we explore the pertinence of this non-cell-autonomous mechanism in human ALS.


METHODS
The levels and expression pattern of IFNγ, LIGHT, and LT-βR were investigated by Western blot and immunohistochemical analysis in spinal cord of patients with sporadic ALS.


RESULTS
We observed significant increased levels of IFNγ in human ALS spinal cords compared to control cases. We found that large ventral horn neurons as well as glial cells were immunoreactive for IFNγ in sporadic ALS spinal cord. We further observed that LIGHT and LT-βR were expressed mainly by motoneurons in both ALS and control cases, and while LT-βR levels remained constant between ALS and control cases, LIGHT levels were increased in human ALS spinal cords.


CONCLUSIONS
These findings in sporadic ALS cases, which are consistent with the observation made in ALS experimental models, propose that the IFNγ-triggered LIGHT/LT-βR-mediated death pathway may contribute to human ALS pathogenesis.
The Mediterranean Institute of Neurobiology, INMED, Marseille, France.
J
J
Aebischer
A
A
Moumen
V
V
Sazdovitch
D
D
Seilhean
V
V
Meininger
C
C
Raoul
D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013116:Spinal Cord / Q000378:metabolism*; D018709:Statistics, Nonparametric; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000378:metabolism*
D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D007371:Interferon-gamma