Lead acetate induces hippocampal pyramidal neuron degeneration in mice via up-regulation of executioner caspase-3, oxido-inflammatory stress expression and decreased BDNF and cholinergic activity: Reversal effects of Gingko biloba supplement

Abstract

PurposeIt has been hypothesized that compounds with strong anti-oxidant activity might mitigate lead-induced neurotoxicity that resulted to neuronal degeneration.Ginkgo biloba supplement (GB-S) is a neuroactive supplement which has been reported to demonstrate neuroprotective effects. In this study, we investigated the reversal effect and the underlying mechanism of GB-S following lead-induced neurotoxicity in mice. MethodsMale Swiss mice (n = 8) were pre-treated with lead acetate (100 mg/kg) for 30 min before GB-S (10 mg/kg and 20 mg/kg) or Ethylenediaminetetraacetic acid (EDTA) (50 mg/kg) intraperitoneally for 14 consecutive days. Memory impairment symptoms were evaluated on day 13 and 14 using Y-maze and Novel object recognition test (NORT) respectively. Thereafter, spectrophotometry, ELISA, immunohistochemistry and histomorphormetry were used to estimate the degree and expression of biomarkers of neuronal inflammation: oxido-inflammatory stress, apoptosis and degeneration in the hippocampus (HC). ResultsLead acetate treatment significantly (p < 0.05) induced neurobehavioral impairment which was reversed by GB-S as evident in increased percentage alternation and discrimination index. GB-S significantly (p < 0.05) reduced lipid peroxidation and nitrite level, inhibited TNF-α and acetylcholinesterase activity and improved glutathione, catalase and superoxide dismutase activity in the HC. Moreover, GB-S inhibited hippocampal apoptosis via elevated expression of caspase-3 with marked increase level of brain derived neurotrophic factor (BDNF). Also, the histomorphormetric study showed that GB-S rescued death of pyramidal neurons (CA3) in the HC. ConclusionOur findings however suggest that GB-S decreased memory impairment progression induced by lead acetate via mechanisms connected to inhibition of oxido-inflammatory stress mediators, restrained acetylcholinesterase activity, up-regulated BDNF/Caspase-3 expression and suppression of hippocampal pyramidal neuron degeneration in mice.