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

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

  • Neurochem Res. 2025 Jan 3;50(1):70. doi: 10.1007/s11064-024-04322-6.
Mei Liang # 1 Mingyu Huang # 1 Jiajia Yu 1 Shan Li 1 2 Danni Zhang 1 Yong Ye 1 Li Chen 3 4 Yan Zhou 5 6
Affiliations

Affiliations

  • 1 College of Pharmacy, Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, China.
  • 2 Nursing College, Guangxi Medical University, Nanning, 530021, China.
  • 3 Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, China. chenliqfkk@163.com.
  • 4 Guangxi Key Laboratory of Regenerative Medicine and Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, China. chenliqfkk@163.com.
  • 5 College of Pharmacy, Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, China. zhouyan@gxmu.edu.cn.
  • 6 Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, China. zhouyan@gxmu.edu.cn.
  • # Contributed equally.
Abstract

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.

Keywords

Apoptosis; Cognitive impairment; HIV-1 envelope glycoprotein gp120; NMDA; PKR inhibitor C16.

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