Dietary Starch Composition Effects on Cx43-intercellular Communication Channels and Short-Term Memory

Abstract

Abstract Objectives Intercellular communication mediated by gap junctions is critical for cognitive and sensory functions and is disturbed with age and age-related diseases. We analyzed the impact of consuming a high glycemic diet or a low glycemic dietary intervention on Cx43, a component of gap junction intercellular communication channels associated with spatial short-term memory, in different age groups of mice. Methods Male C57Bl6/J mice (n = 12–13) aged 7 months were fed equal amounts of either a high glycemic (HG) diet or a low glycemic (LG) diet for 1 month or 9 months. Within the 9-month feeding trial, half of the HG-fed animals were switched to the LG diet (HGxLG) at 4.5 months. The diets are isocaloric, but the HG starch is 100% composed of amylopectin, and the LG diet contains a 30% amylopectin/70% amylose mixture of starch and is digested much slower. We also analyzed tissues from a previous feeding trial where 12-month aged animals were fed these same diets over 12 months. The animals were weighed weekly, underwent intraperitoneal glucose tolerance tests to evaluate glycemic response, were tested for cognition using a novel object recognition test, and tissues were collected. Tissues including brain and eye samples were evaluated for Cx43, a component of gap junction intercellular communication channels, using immunohistochemistry and western blotting. Results At both time points, compared to the LG-fed controls, the HG-fed animals had significantly increased (>10%) body weight, while the HGxLG crossover animals’ body weight did not differ significantly from the LG-fed controls at 15 months. At 14 months, there was no significant difference in novel object recognition, although there was a trend of improved novel object recognition in the HGxLG crossover group. Cx43 gap junction protein accumulated in eye tissues of the HG-fed animals, and this accumulation was attenuated in the HGxLG group. Conclusions These results suggest that detrimental consequences of a high glycemic diet during aging on cognitive function may be reversible, supporting that a switch in dietary habits may be an effective nutritional intervention in older adults. Funding Sources USDA JM HNRCA Pilot Grant Program, NIH, USDA NIFA, USDA, Thome Memorial Foundation, and the BrightFocus Foundation.