Abstract
Genistein (GE) or 4′,5,7-trihydroxyflavone, a plant derived isoflavone, is a biologically active compound having several beneficial properties. Studies showed that GE possesses anti-neoplastic, anti-tumor, anti-helminthic, anti-oxidant, and anti-inflammatory activities. Herein, we investigated the neuroprotective effects of GE in a mouse model of hypoxia-induced amnesia. Mice were exposed to hypoxic conditions (10% O2) in a designated hypoxia chamber and co-treated with GE (10, 20, or 30 mg/kg) for 4 weeks. Following this, behavioral tests were performed to evaluate memory performance. We assessed microglial activation in the hippocampus, amygdala, and pre-frontal cortex (PFC) regions by evaluating the Iba-1 and GFAP transcript levels, and MIP-1β, Cox-2, and IL6 protein levels. Apoptosis was assessed by evaluating Bax, BAD, and Bcl-2 mRNA levels, and caspase-3 activity. To uncover the underlying molecular mechanism, we evaluated the levels of Nrf2, HO-1, and NQO1 in different brain regions of mice from all groups. Results showed that hypoxia-exposed mice have reduced performance in the behavioral tests and GE treatment enhanced the memory performance in hypoxia-exposed mice. Moreover, hypoxia-exposed mice showed increased expression of microglial activation markers and enhanced apoptosis in the hippocampus, amygdala, and PFC. GE treatment suppressed microglial activation and prevented apoptosis in the brain of hypoxia-exposed mice. Furthermore, hypoxia-exposure reduced the expression of Nrf2, NQO1, and HO-1 while GE treatment ameliorated this decrease in different regions of hypoxia-exposed mice brain. In conclusion, GE prevents cognitive dysfunction by suppressing microglial activation and inhibiting apoptosis in the hypoxia-exposed mice brain.
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This study was supported by the Grain-in-Aid from Science and Engineering Research Board (SERB), India (Grant No: EMR/2017/000282).
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MR and SP designed the study. MR performed the experiments, analyzed the data, and wrote the manuscript. MG helped in animal studies. BS, SP, AAM helped in revising the manuscript. All authors have read and approved the manuscript for submission.
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Rumman, M., Pandey, S., Singh, B. et al. Genistein suppresses microglial activation and inhibits apoptosis in different brain regions of hypoxia-exposed mice model of amnesia. Metab Brain Dis 37, 2521–2532 (2022). https://doi.org/10.1007/s11011-022-01039-9
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DOI: https://doi.org/10.1007/s11011-022-01039-9