p75NTR-dependent, myelin-mediated axonal degeneration regulates neural connectivity in the adult brain

摘要: Axonal degeneration is important during development but has not been thought to function in the intact mature nervous system. Here, we provide evidence that of adult axons occurs rodent brain through a p75 neurotrophin receptor (p75NTR)- and myelin-dependent mechanism. Specifically, show p75NTR-mediated axonal prevents septal cholinergic from aberrantly growing onto myelinated tracts vivo or on myelin substrate culture. Myelin also triggers local p75NTR-expressing sympathetic rescued by increasing TrkA signaling elevating intracellular cyclic AMP. Myelin-mediated when neurotrophins bind p75NTR, involves p75NTR-dependent sequestration Rho guanine nucleotide dissociation inhibitor (Rho-GDI). Moreover, degeneration, growth inhibition, requires downstream activation caspase-6. These data indicate p75NTR maintains specificity neural connectivity preventing inappropriate sprouting physiological explanation for inhibition after injury.