Fig. 13

A new model for Tat-impaired neurite outgrowth. Tat impairs neurite outgrowth through its uptake into neurons, CREB phosphorylation (pCREB), miR-132 induction, and MecP2 and BDNF down-regulation. Alternatively, Tat-impaired neurite outgrowth results from HIV-1 infection and Tat expression in astrocytes, pCREB, miR-132 induction, and BDNF down-regulation. miR-132 induction in astrocytes increases exosome-associated miR-132 release from astrocytes, uptake of exosome-associated miR-132 into neurons, and MecP2 and BDNF down-regulation of MecP2 in neurons. In addition, BDNF down-regulation in astrocytes deprives neurons of BDNF, which further impairs neurite outgrowth and neuron survival