Interleukin-6 promotes sprouting and functional recovery in lesioned organotypic hippocampal slice cultures.
Interleukin (IL)-6 is a pro-inflammatory cytokine now widely recognized to contribute to the molecular events that follow CNS injury. Little is known, however, about its action on axonal sprouting and regeneration in the brain. We addressed this issue using the model of transection of Schaffer collaterals in mice organotypic hippocampal slice cultures. Transection of slice cultures was associated with a marked release of IL-6 that could be neutralized by an IL-6 blocking antibody. We monitored functional recovery across the lesion by recording synaptic responses using a multi-electrode array. We found that application of IL-6 antibodies to the cultures after lesioning significantly reduced functional recovery across the lesion. Furthermore, the level of expression of the 43-kDa growth-associated protein (GAP-43) was lower in slices treated with the IL-6 neutralizing antibody than in those treated with a control IgG. Conversely, addition of exogenous IL-6 to the culture medium resulted in a dose-dependent enhancement of functional recovery across the lesion and a higher level of expression of GAP-43. Co-culture of CA3 hemi-slices from thy1-YFP mice with CA1 hemi-slices from wild-type animals confirmed that IL-6-treated co-cultures exhibited an increased number of growing fluorescent fibres across the lesion site. Taken together these data indicate that IL-6 plays an important role in CNS repair mechanisms by promoting regrowth and axon regeneration.
Hakkoum
David
D
Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland. david.hakkoum@medecine.unige.ch
Stoppini
Luc
L
Muller
Dominique
D
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D019771:Axotomy; D001925:Brain Damage, Chronic / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D019922:GAP-43 Protein / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D009416:Nerve Regeneration / Q000187:drug effects / Q000276:immunology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000276:immunology*; D009924:Organ Culture Techniques; D020127:Recovery of Function / Q000187:drug effects / Q000276:immunology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000276:immunology; D000093242:Interleukin-6 Inhibitors
D000906:Antibodies; D019922:GAP-43 Protein; D015850:Interleukin-6; D009414:Nerve Growth Factors; D000093242:Interleukin-6 Inhibitors