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Archives of Biological Sciences 2015 Volume 67, Issue 2, Pages: 639-646
https://doi.org/10.2298/ABS140811023X
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Protective effect of naringenin on glutamate-induced neurotoxicity in cultured hippocampal cells

Xu Xiao-Hui (Luoyang Central Hospital Affiliated to Zhengzhou University, Department of Neurology, Luoyang, PR China)
Ma Cong-Min (Luoyang Central Hospital Affiliated to Zhengzhou University, Department of Neurology, Luoyang, PR China)
Han Yue-Zhen (Luoyang Central Hospital Affiliated to Zhengzhou University, Department of Neurology, Luoyang, PR China)
Li Yans (Luoyang Central Hospital Affiliated to Zhengzhou University, Department of Neurology, Luoyang, PR China)
Liu Chao (Luoyang Central Hospital Affiliated to Zhengzhou University, Department of Neurology, Luoyang, PR China)
Duan Zhi-Hui (Luoyang Central Hospital Affiliated to Zhengzhou University, Department of Neurology, Luoyang, PR China)
Wang Hui-Lin (Luoyang Central Hospital Affiliated to Zhengzhou University, Department of Neurology, Luoyang, PR China)
Liu De-Quan (Luoyang Central Hospital Affiliated to Zhengzhou University, Department of Neurology, Luoyang, PR China)
Liu Rui-Hua (Luoyang Central Hospital Affiliated to Zhengzhou University, Department of Neurology, Luoyang, PR China)

Monosodium glutamate induces excitotoxicity in the central nervous system through hyperactivation of both ionotropic and metabotropic glutamate receptors, which leads to neuronal cell death. In this study, we investigated the neuroprotective effects of naringenin on excitotoxicity induced by glutamate in primary hippocampal neurons of neonatal mice. The expression levels of apoptosis-inducing proteins and as well as ischemic factors were observed by Western blot analysis. Immunocytochemistry and morphometric analysis of hippocampal cells with or without glutamate and naringenin treatment were performed. We observed that naringenin regulated Erk1/2 and Akt phosphorylation and reduced the demise of dendrites due to glutamate exposure in cultured hippocampal neurons. Furthermore, naringenin induced the brain-derived neurotrophic factor and other neuroprotective cytokines, and markedly improved the survival rates of the neurons 24 h following glutamate exposure. The observed results suggest that the naturally occurring bioflavonoid (naringenin) exerts neuroprotective effects via highly specific molecular targets in neurons.

Keywords: excitotoxicity, glutamate, hippocampal neuronal cells, naringenin, neuroprotection