neuroimmunology-2017-keynote

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Page 27
ISSN:2171-6625
September 18-19, 2017 | Dallas, USA
4th International Conference on
NEUROLOGY AND NEUROIMMUNOLOGY
Notes:
Denis Gris
Université de Sherbrooke, Canada
Computerized behavioral assessments of novel model of multiple sclerosis
Multiple sclerosis is an autoimmune disease of the
central nervous system. Recently, we have discovered
an endogenous pathway that limits inflammation multiple
sclerosis-likediseaseinmice.Oneofthekeymoleculesofthese
pathways is Nlrx1 that belongs to Nlr family of proteins. Nlrs
bind multiple proteins inside cells thus redirecting molecular
signaling. Using state-of-the-art automated behavioral
platform, we demonstrate that Nlrx1 inhibit progression of
the diseases in a mouse model of MS. Furthermore, we were
able to construct mice with increased predisposition to MS.
These mice demonstrate the spontaneous appearance of the
disease without any immunization. This model helped us to
dissociate sickness behavioral profile from the behavioral
signature of neuroinflammation. In addition, our results
suggest that predisposition may rise from the disturbed
homeostasis in the central nervous system rather than the
peripheral activation of immune system. We observed that
the inflammatory effect of Nlrx1 at the mitochondrial level,
in inflammatory cells such as microglia and astrocytes, results
in inhibition of assembly of proinflammatory pathways
including Type I interferon and NFkB. Accordingly, we
observed the reduction in the expression of iNOS, cytokines
including IL-1beta and TNF-alpha duringmicroglial activation.
In neurons, Nlrx1 effect results in inhibition of necrosis and
increased viability. Using N2A cell line, we demonstrated that
Nlrx1 protects cells from rotenone toxicity. We demonstrated
that Nlrx1 overexpressing cells were more viable than Nlrx1
KO cells and the ratio of apoptosis to necrosis was shifted
to necrosis in cells that lacked Nlrx1. In conclusion, our
study demonstrates that targeting central nervous system
innate immune responses presents promising novel strategy
treatments of multiple sclerosis.
Speaker Biography
Denis Gris has started his scientific career with the Master’s and PhD in Neuroscience
at Dr. Lynn Weaver’s laboratory at the University of Western Ontario. He studied
the role of inflammation in spinal cord injury. He discovered that the influx of
neutrophils is detrimental for recovering after spinal cord injury. Using anti CD11d
antibody as a treatment, he demonstrated that animals recovered faster and better
after the treatment. Also, he showed that sever spinal cord injury results in massive
inflammatory reactions throughout the body leading to syndrome similar to multiple
organ dysfunction syndrome. He continued his education in Dr. Jenny P-Y Ting’s
laboratory as a Post-doctoral fellow at the University of North Carolina at Chapel Hill.
There, he studied in detail mechanism of activation of innate and adoptive immune
responses. In collaboration with Dr. Wen, Dr. Eitas, Dr. Allen, and other members of the
laboratory, he studied inflammation during obesity which leads to insulin resistance;
innate and adoptive responses during multiple sclerosis. In summary, his role in this
laboratory was to define the role of novel family of immuno regulatory proteins (NLRs)
in different human diseases. Currently, he is a member of Immunology Program at the
University of Sherbrooke and is studying neuro-immune interactions during healthy
state and disease.
e:
Denis Gris, J Neurol Neurosci, 8:5
DOI: 10.21767/2171-6625-C1-001