Food restriction induces long-lasting recovery of spatial memory deficits following global ischemia in delayed matching and non-matching-to-sample radial arm maze tasks

Food restriction has been shown to be beneficial for a number of brain processes. In the current study, we characterized the impact of food restriction on hippocampal damage 70 days following ischemia. We assessed memory and cognitive flexibility of ad libitum fed (AL) and food-restricted (FR) animals using complex delayed non-matching- and matching-to-sample tasks in the radial arm maze. Our findings demonstrate that food restriction led to significant improvement of ischemia-induced memory impairments. FR ischemic animals rapidly reached comparable performance as both AL and FR sham animals in delayed-non-matching (win-shift) and matching (win-stay) radial arm maze tasks. They also made considerably fewer microchoices in the retention trials than AL ischemic animals. In contrast, AL ischemic rats showed persistent spatial memory impairments in the same paradigms. Assessment of basal and stress-induced corticosterone (CORT) secretion revealed no significant differences in baseline levels in AL and FR rats prior to or following global ischemia. However, FR animals showed a more pronounced attenuation of CORT secretion 45 min following restraint. Both FR and AL ischemic rats had comparable cell loss within CA1 and CA3 subfields of Ammon's horn (CA1 and CA3) at 70 days following reperfusion, although a trend toward increased CA3 cell survival was observed in FR ischemic rats. The functional sparing in the FR ischemic animals in the face of equivalent hippocampal cell loss suggests that food restriction somehow enhanced the efficacy of remaining hippocampal or extrahippocampal neurons following ischemia. In the current study, this phenomenon was not associated with diet- and or ischemia-related alterations of vesicular glutamate transporter 1 expression in various hippocampal regions although lower vesicular GABA transporter immunostaining was present in the CA1 stratum oriens and the CA3 stratum radiatum in FR sham and ischemic rats.