Reduction in parvalbumin-positive interneurons and inhibitory input in the cortex of mice with experimental autoimmune encephalomyelitis.
In multiple sclerosis (MS), inflammation leads to damage of central nervous system myelin and axons. Previous studies have postulated impaired GABA transmission in MS, and recent postmortem analysis has shown that GABAergic parvalbumin (PV)-positive interneurons are decreased in the primary motor cortex (M1) of patients with MS. In this report, we present evidence for the loss of a specific population of GABAergic interneurons in the experimental autoimmune encephalomyelitis mouse model of MS. Using experimental autoimmune encephalomyelitis, we evaluated the distribution of both PV-positive interneurons and of the inhibitory presynaptic input in the M1 of experimental autoimmune encephalomyelitis and control mice. Our results demonstrate a specific decrease in the number of PV-positive interneurons in the M1 of mice with experimental autoimmune encephalomyelitis. We detected a significant reduction in the number of PV-positive interneurons in the layers II and III of the M1 of diseased mice, while there was no difference in the number of calretinin (CR)-positive cells between animals with experimental autoimmune encephalomyelitis and control animals. Moreover, we observed a significant reduction in the inhibitory presynaptic input in the M1 of treated mice. These changes were specific for the mice with elevated clinical score, while they were not detectable in the mice with low clinical score. Our results support the hypothesis that reinforcing the action of the GABAergic network may represent a therapeutic alternative to limit the progression of the neuronal damage in MS patients.
Cell Adhesion Unit, Division of Neuroscience, San Raffaele Scientific Institute, via Olgettina, 58-20132, Milan, Italy.
Anna
A
Falco
Roberta
R
Pennucci
Elena
E
Brambilla
Ivan
I
de Curtis
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007395:Interneurons / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009044:Motor Cortex / Q000473:pathology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D009433:Neural Inhibition / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism*; D010446:Peptide Fragments / Q000633:toxicity; D013997:Time Factors; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010320:Parvalbumins; D010446:Peptide Fragments; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C445081:myelin oligodendrocyte glycoprotein (35-55); C493406:vesicular GABA transporter; D017493:Leukocyte Common Antigens