PKR Inhibitor C16 Regulates HIV-gp120 Induced Neuronal Injury and Cognitive Impairment in Vivo and in Vitro Models.

To study the neuronal protective effect and its potential mechanism of C16 against gp120-induced cognitive impairment in vitro and in vivo. The NORT method was used to evaluate the short-term memory abilities of rats, the morphological changes in hippocampus were observed by Nissl staining. Cell viability and damage degree were detected by MTT and LDH. The cell living/apoptosis status of PC12 cells was determined by AO/EB double staining and the relative mRNA expressions of PKR, IRE1α, JNK, GRP78, and CHOP were detected by RT-qPCR. In comparison with the gp120 + Memantine and gp120 + C16 groups, the rats in the gp120 group showed a significantly decreased discrimination index (P < 0.001), with disordered CA1 region cells and reduced neuron numbers. AO/EB double staining revealed morphological changes in the gp120 and NMDA groups, while cells in the gp120 + C16 and NMDA + C16 groups resembled the control group. And C16 can significantly down-regulate the mRNA expression levels of PKR, IRE1α, JNK, GRP78, and CHOP. (P < 0.05). C16 can reduce the cognitive impairment stimulated by gp120 or NMDA, the protective mechanism may be correlated with inhibiting the upregulation of PKR/IRE1α/JNK pathway and suppressing apoptosis induced by downstream proteins GRP78 and CHOP.