Oral administration of magnesium-L-threonate prevents vincristine-induced memory and emotional deficits
Objective:To observe the impact of magnesium-L-threonate(L-TAMS)on vincristine(VCR)-induced memory and emotional deficits in rats and to explore its mechanisms.Methods:SD rats were randomly divided into three groups using the random number table method:the Control group(drinking normal water and receiving an equal amount of saline injection),the VCR group(rats injected intraperitoneally with vincristine and drinking normal water),and the L-TAMS+VCR group(L-TAMS as added to the drinking water from 7 days before VCR injection until the end of the experiment),with 5-7 rats in each group.The novel object recognition test(NORT)assessed the memory of SD rats;the elevated plus-maze test(EPMT)evaluated anxiety behaviors;the forced swimming test(FST)assessed depressive behaviors in SD rats.The amplitude of hippocampal CA3-CA1 postsynaptic evoked field potentials was recorded using in vivo electrophysiological experimental techniques;Western blot determined the expression of N-methyl-D-aspartate receptors(NMDARs)subunit NR2B in the hippocampus.Immunofluorescence evaluated the expression of microglia in the CA1 of hippocampus and an-terior cingulate cortex(ACC).Results:Compared to the Control group,the VCR group exhibited a decrease in recognition index,an increase in immobility time,a reduction in the time and frequency of entering the open arms of elevated plus-maze,a decrease in the amplitude of synaptic potentials in the CA3-CA1 region of the hippocampus,a significant reduction of the expression of NR2B in the hippocampus,and an increased expression of glial cells in the CA1 region and the ACC of the hippocampus.Oral administration of L-TAMS starting 7 days prior to intraperitoneal injection of VCR until the end of the experiment prevented the aforementioned changes induced by VCR.Conclusion:L-TAMS can reverse the significant reduction in CA3-CA1 postsynaptic field potentials induced by VCR by upregulating the N-methyl-D-aspartate receptor subunit NR2B in the hippocampal postsynaptic membrane,improving impaired hippocampal synaptic transmission,and reducing the expression of microglia in CA1 and ACC,alleviating neuroinflammatory,thus further preventing VCR-induced memory and emotional functional deficits.
magnesium-L-threonatevincristinememory and emotional deficitshippocampusanterior cingulate cortexsynaptic plasticityneuroinflammatory
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