Paliperidone protects prefrontal cortical neurons from damages caused by MK-801 via Akt1/GSK3β signaling pathway

Lei Peng, Dexiao Zhu, Xiaowen Feng, Haiman Dong, Qingwei Yue, Jing Zhang, Qing Gao, Jing Hao, Xingzhen Zhang, Zengxun Liu, Jinhao Sun

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Recent studies have suggested that neurodegeneration is involved in the pathogenesis of schizophrenia, and some atypical antipsychotics appear to prevent or retard progressive morphological brain changes. However, the underlying molecular mechanisms are largely unknown. Whether changes in intracellular signaling pathways are related to their neuroprotective effects remains undefined. In the present study, we used mouse embryonic prefrontal cortical neurons to examine the neuroprotection of paliperidone against the neuronal damage induced by exposure to the NMDA receptor antagonist, MK-801. Paliperidone inhibited MK-801 induced neurotoxicity both in MTT metabolism assay (p<0.01) and in lactate dehydrogenase (LDH) activity assay (p<0.01). Time course studies reveled that paliperidone effectively attenuated the elevation of intracellular free calcium concentration ([Ca2+]i) induced by exposure to MK-801 (p<0.01). Moreover, paliperidone could significantly retard MK-801-mediated inhibition of neurite outgrowth (p<0.01) and reverse MK-801-induced decreases of gene expression and phosphorylation of Akt1 and GSK3β (both p<0.01). Furthermore, these protective effects of paliperidone were blocked by pretreatment with a PI3K inhibitor LY294002. Taking together, our results demonstrated that paliperidone could protect prefrontal cortical neurons from MK-801-induced damages via Akt1/GSK3β signaling pathway.

Original languageEnglish (US)
Pages (from-to)14-23
Number of pages10
JournalSchizophrenia research
Volume147
Issue number1
DOIs
StatePublished - Jun 2013
Externally publishedYes

Keywords

  • Paliperidone
  • Prefrontal cortical neurons
  • Protection
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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