Journal
ANTIOXIDANTS
Volume 11, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/antiox11091697
Keywords
olanzapine; transient ischemia; oxidative stress; neuroprotection; antioxidant; MAPK; differentially expressed genes (DEGs)
Funding
- National Research Foundation of Korea (NRF) - Korean government (MIST) [NRF-2020R1F1A1076246]
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Olanzapine has neuroprotective effects through downregulating complement component-related genes and MAPKs expression, upregulating SOD expression, reducing ROS generation, and regulating apoptosis-related protein expression.
Olanzapine (OLNZ) is used to treat psychotic disorders. To look into the neurological basis of this phenomenon, we investigated the neuroprotective effects of OLNZ in gerbils and SH-SY5Y cells. Gerbils were subjected to transient global cerebral ischemia (TGCI) by blocking both common carotid arteries, and OLNZ (10 mg/kg) was injected intraperitoneally. Hydrogen peroxide (H2O2) was used to induce oxidative-stress-mediated damage in the SH-SY5Y cells. The results indicated that OLNZ administration markedly reduced neuron damage and glial cell triggering within CA1 zone of the hippocampus. We used RNA sequencing to assess the numbers of up-and downregulated genes involved in TGCI. We found that OLNZ treatment downregulated the expression of complement-component-related genes and the expression of mitogen-activated protein kinases (MAPKs) in the hippocampus. In cells, OLNZ co-treatment significantly improved cell viability and reduced lactate dehydrogenase (LDH), and reactive oxygen species (ROS) generation. Expression of antioxidant superoxide dismutase-1,2 enzymes (SOD-1, SOD-2) was also intensely upregulated by OLNZ, while the expression of MAPKs and NF-kappa B were reduced. Co-incubation with OLNZ also regulated apoptosis-related proteins Bax/Bcl-2 expression. Finally, the results demonstrated that treatment with OLNZ showed neuroprotective effects and that the MAPK pathway could involve in the protective effects.
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