Mechanisms and time course of neuronal degeneration in experimental autoimmune encephalomyelitis.
Neuronal and axonal damage is considered to be the main cause for long-term disability in multiple sclerosis. We analyzed the mechanism and kinetics of neuronal cell death in experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) by combining an electrophysiological in vivo assessment of the optic pathway with the investigation of retinal ganglion cell (RGC) counts. In accordance with our previous findings in this animal model, neuritis of the optic nerve (ON) leads to apoptotic RGC death. By further investigating the time course of RGC apoptosis in the present study, we found that neuronal cell death together with decreased visual acuity values occurred before the onset of clinical symptoms. Simultaneously with the time course of RGC apoptosis, we found a down-regulation of phospho-Akt as well as a shift in the relation of 2 proteins of the Bcl-2 family, Bax and Bcl-2, towards a more proapoptotic ratio in these cells. Comparing the kinetics and mechanisms of RGC death during MOG-EAE with those following complete surgical transection of the ON, we found significant agreement. We hypothesize that the main reason for RGC loss in MOG-EAE is the inflammatory attack but RGC death also occurs independently of histopathological ON changes.
Hobom
Muriel
M
Neurologische Universitätsklinik, Robert-Koch-Str. 40, 37075 Göttingen, Germany. mhobom@gwdg.de
Storch
Maria K
MK
Weissert
Robert
R
Maier
Katharina
K
Radhakrishnan
Anand
A
Kramer
Birgit
B
Bähr
Mathias
M
Diem
Ricarda
R
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002452:Cell Count; D004594:Electrophysiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D009410:Nerve Degeneration / Q000473:pathology* / Q000503:physiopathology; D009900:Optic Nerve / Q000473:pathology* / Q000503:physiopathology; D020221:Optic Nerve Injuries / Q000473:pathology; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D012165:Retinal Ganglion Cells / Q000473:pathology*; D013997:Time Factors
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt