CNS lesions are often followed by structural reorganization within intact circuits of the brain. In parallel, focal lesions also induce neuroinflammatory reaction that encourages the understanding of the mechanisms shared between neuroplasticity and immune activation, within CNS injury context. TNF-? is a key proinflammatory cytokine that exerts its effects via TNF receptor subtype-1 (TNFR1) or -2 (TNFR2). Calcineurin (CaN) is a phosphatase related to synaptic pruning and immune function, that mediates microglia activation and TNF-a release. Here we evaluated the role of TNF-a and microglia on the sprouting of intact retinotectal axons following monocular enucleation (ME) and the temporal expresion of TNFR1/2 after lesion. Lister Hooded rats were submitted to ME at P10 and evaluated in different survival times. Animals also received systemic injections of cyclosporin A (50mg/kg,sc) or minocycline (125 mg/kg,sc) 3h following ME. A third group received local delivery (ELVAX) of a TNF-a neutralizing antibody 3 days before. Neuroanatomical tracers mapped structural plasticity while immunofluorescence and western blot were used to study microglia morphology, TNF-a, TNFR1/2 and CaN content. A progressive increase of activated microglia in the contralateral superior colliculus (SC) 24h after ME, peaking at 72h presented a temporal correlation with an increase in TNFR1 and TNFR2 immunoreactivity, that ceased 7d after. Inhibition of microglia or TNF-a reduced sprouting of intact uncrossed retinotectal axons, amoeboid microglia and TNF-a expression. Our data support the hypothesis that TNF-a signalling is regulated during a microglia-dependent neuroplasticity induced by lesions during early brain development. Approved by local animal care committee (CEUA/UFF: protocol 0015109).
Comissão Organizadora
Ciências e Cognição
Comissão Científica
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