Abstract
BackgroundCadmium leads to learning and memory impairment. Dendropanax morbifera Léveille stem extract (DMS) reduces cadmium-induced oxidative stress in the hippocampus. We investigated the effects of DMS on cadmium-induced impairments in memory in rats.MethodsCadmium (2 mg/kg), with or without DMS (100 mg/kg), was orally administered to 7-week-old Sprague-Dawley rats for 28 days. Galantamine (5 mg/kg), an acetylcholinesterase inhibitor, was intraperitoneally administered as a positive control. A novel-object recognition test was conducted 2 h after the final administration. Cell proliferation and neuroblast differentiation were assessed by immunohistochemistry for Ki67 and doublecortin, respectively. Acetylcholinesterase activity in the synaptosomes of the hippocampus was also measured based on the formation of 5,5′-dithio-bis-acid nitrobenzoic acid.ResultsAn increase in the preferential exploration time of new objects was observed in both vehicle-treated and cadmium-treated rats. In addition, DMS administration increased cell proliferation and neuroblast differentiation in the dentate gyrus of vehicle-treated and cadmium-treated rats. Acetylcholinesterase activity in the hippocampal synaptosomes was also significantly higher in the DMS-treated group than in the vehicle-treated group. The effect of DMS on cadmium-induced memory impairment and cell proliferation in the hippocampus was comparable to that of galantamine.ConclusionsThese results suggest that DMS ameliorates cadmium-induced memory impairment via increase in cell proliferation, neuroblast differentiation, and acetylcholinesterase activity in the hippocampus. The consumption of DMS may reduce cadmium-induced neurotoxicity in animals or humans.
Highlights
Cadmium leads to learning and memory impairment
Effects of cadmium with or without Dendropanax morbifera Léveille stem extract (DMS) on recognition memory During the training period, all rats showed similar behavioral patterns and spent a similar fraction of time exploring the identical objects, the cadmiumtreated group, with or without DMS, showed less activity exploring the objects compared to the control group
In the cadmium-treated group, rats spent a similar amount of time exploring new and familiar objects and the discrimination index (DI) was decreased significantly compared to that in the control group
Summary
Cadmium leads to learning and memory impairment. We investigated the effects of DMS on cadmium-induced impairments in memory in rats. Proliferating cells with active cell cycles in the subgranular zone of the dentate gyrus express Ki67 [5] and adult-born neuroblasts express doublecortin (DCX) from days 1 to 28 of cell age [6, 7]. Adult neurogenesis is required only when the reactivation session involves novelty and this process drives the updating of stored object recognition memories. Stimulation of endogenous hippocampal neurogenesis reinforces the hippocampal network and improves learning and memory, whereas ablation of hippocampal neurogenesis by γ-ray irradiation of the dentate gyrus leads to cognitive impairment [10,11,12,13]. The inhibition of WNT signaling by dominant-negative WNT significantly reduces novel-object recognition memory [13]
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