Neuronal NF-¦ÊB ablation does not influence neuro-axonal degeneration in experimental autoimmune demyelination

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• 作者：De-Hyung Lee^a ; ^b ; Katharina Kubera^c ; Bastian Rosenthal^a ; Barbara Kaltschmidt^d ; Christian Kaltschmidt^e ; Ralf Gold^a ; Ralf A. Linker^a ; ^b ; ^{ralf.linker@uk-erlangen.de}
• 关键词：CNS ; central nervous system ; EAE ; experimental autoimmune encephalomyelitis ; L ; lesion ; MOG ; myelin oligodendrocyte glycoprotein ; MS ; multiple sclerosis ; NAWM ; normal appearing white matter ; PFA ; paraformaldehyde ; p.i. ; post immunization ; PL ; perilesion
• 刊名：Journal of Neuroimmunology
• 出版年：2012
• 出版时间：15 May, 2012
• 年：2012
• 卷：246
• 期：1-2
• 页码：38-42
• 全文大小：745 K

文摘

Neuro-axonal damage is a major hallmark of multiple sclerosis (MS). To date, not much is known on the underlying mechanisms of neuronal degeneration. In disease model myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis (MOG-EAE), there is a significant loss of alpha motorneurons in the cervical as well as thoracic and lumbar spinal cord. We further investigate the role of activated NF-¦ÊB for neuronal damage in a conditional ablation mouse model. A calcium calmodulin kinase II promoter-driven tetracycline transactivator is employed to regulate the expression of a human transdominant negative I¦ÊB-alpha mutant in the basal forebrain and selected neuronal subpopulations in the cerebellum and spinal cord including cerebellar Purkinje cells and spinal cord alpha motorneurons. In these mice with conditional neuronal NF-¦ÊB ablation, the clinical course of MOG-EAE, parameters of inflammation and axonal densities in the spinal cord white and grey matter as well as numbers of alpha motorneurons are not different to littermate controls. In conclusion, neuronal NF-¦ÊB ablation does not modulate neurodegeneration in autoimmune demyelination.