Impairment of Novel Object Recognition Memory and Brain Insulin Signaling in Fructose- but Not Glucose-Drinking Female Rats

Abstract

Excessive sugar intake has been related to cognitive alterations, but it remains unclear whether these effects are related exclusively to increased energy intake, and the molecular mechanisms involved are not fully understood. We supplemented Sprague-Dawley female rats with 10% w/v fructose in drinking water or with isocaloric glucose solution for 7 months. Cognitive function was assessed through the Morris water maze (MWM) and the novel object recognition (NOR) tests. Plasma parameters and protein/mRNA expression in the frontal cortex and hippocampus were determined. Results showed that only fructose-supplemented rats displayed postprandial and fasting hypertriglyceridemia (1.4 and 1.9-fold, p < 0.05) and a significant reduction in the discrimination index in the NOR test, whereas the results of the MWM test showed no differences between groups. Fructose-drinking rats displayed an abnormal glucose tolerance test and impaired insulin signaling in the frontal cortex, as revealed by significant reductions in insulin receptor substrate-2 protein levels (0.77-fold, p < 0.05) and Akt phosphorylation (0.72-fold, p < 0.05), and increased insulin-degrading enzyme levels (1.86-fold, p < 0.001). Fructose supplementation reduced the expression of antioxidant enzymes and altered the amount of proteins involved in mitochondrial fusion/fission in the frontal cortex. In conclusion, cognitive deficits induced by chronic liquid fructose consumption are not exclusively related to increased caloric intake and are correlated with hypertriglyceridemia, impaired insulin signaling, increased oxidative stress and altered mitochondrial dynamics, especially in the frontal cortex.

Chronic Consumption of Fructose Induces Behavioral Alterations by Increasing Orexin and Dopamine Levels in the Rat Brain<strong> </strong>

“…Also, it has been described that increased slow oscillatory activity, a hallmark of NREM, is associated with better performance in different tasks of episodic memory and novel objects recognition [40]. It has been described that chronic intake of 10% fructose in drinking water induces impairment of spatial memory and novel object recognition memory [15,20]. Our results show that fructose diet significantly reduces the total time spent in NREM sleep.…”

“…Also, the report of Yin et al [15] showed that rats receiving a lower concentration (10% fructose solution in drinking water) exhibited a significant increase in the escape latency of the Morris water maze test. More recently, a study analyzed other cognitive parameters and showed that fructose supplementation induces an impairment of the novel object recognition memory [20].…”

Consumption of Alcopops During Brain Maturation Period: Higher Impact of Fructose Than Ethanol on Brain Metabolism

“…Brain metabolic remodeling appears to occur precociously without a concurrent increase in overall energy intake and seems consequently to be linked to fructose itself. These disturbances should be more explored to elucidate deleterious long-term outcomes, such as memory impairments, as recently proposed ( 73 ).…”

Chronic Consumption of Fructose Induces Behavioral Alterations by Increasing Orexin and Dopamine Levels in the Rat Brain

“…It has been reported that sleep restriction for 6-h during four days selectively impaired spatial learning and decreased the number of mitotic cells in the hippocampus [ 42 ]. Interestingly, Inostroza et al reported that short periods (80 min) of sleep restriction are enough to decline the consolidation and retrieval of spatial and temporal memories in a novel-object recognition task [ 43 ].It has been described that chronic intake of 10% fructose in drinking water induces impairment of spatial memory and novel object recognition memory [ 15 , 20 ]. Our results show that fructose diet significantly reduces the total time spent in NREM sleep.…”

“…Also, the report of Yin et al [ 15 ] showed that rats receiving a lower concentration (10% fructose solution in drinking water) exhibited a significant increase in the escape latency in the Morris water maze test. More recently, a study analyzed other cognitive parameters and showed that fructose supplementation induces an impairment of the novel object recognition memory [ 20 ].…”