The effect of lithium chloride on the attenuation of cognitive impairment in experimental hypoglycemic rats

Abstract

BACKGROUND\nHypoglycemia is the most common complication in the treatment of diabetes mellitus. Accumulating evidence indicated that severe hypoglycemia could induce cognitive impairment. However, the molecular mechanism of regulating this progress is largely unknown.\n\n\nMETHODS\nWe established a model of insulin-induced recurrent hypoglycemia in adult male Wistar rats (n\u2009=\u200940). Lithium chloride was injected after hypoglycemia once a day for consecutive 30 days. The loss of cognition function was evaluated by water maze test in these hypoglycemic rats. Glial cells activation and Wnt and inflammatory cytokines IL-1β, IL-6, IL-4, IL-10, TGFβ and TNFα expression were further examined to determine the mechanism of cognitive function impairment.\n\n\nRESULTS\nHypoglycemia could induce impairment of cognitive function in rats and administration of lithium chloride could partly attenuate cognitive impairment compared to the control (p\u2009<\u20090.05). Lithium chloride could significantly up-regulate Wnt signaling and reduce hypoglycemia-induced neuronal death, glial cells activation and inflammatory response in the hippocampus of rats compared to the control (p\u2009<\u20090.05). The efficacy of lithium chloride could be reversed by injecting canonical Wnt signaling antagonist the dickkopf homolog 1.\n\n\nCONCLUSION\nLithium chloride attenuated hypoglycemia-induced cognitive function impairment in rats; and it was associated with Wnt signaling up-regulation and reduction of inflammatory response. Our results suggested that activating Wnt signaling pathways and inhibiting inflammatory response were the therapeutic potential to prevent hypoglycemia-induced neurological damage.