Consumo crônico de dieta rica em carboidratos induz alterações comportamentais em camundongos via óxido nítrico

Abstract

The consumption of ultra-processed and high-calorie foods increase every year. As consequence, the overweight and obesity reaches alarming rates and becoming a serious public health problem. Low-grade systemic inflammation is considered an important characteristic of obesity and a characteristic of other comorbidities, such as diabetes type 2, metabolic syndrome, as well as mood-related disorders. Inflammatory mediators, including proinflammatory cytokines, upregulate inducible nitric oxide synthase (iNOS), which in turn increases nitric oxide (NO) formation. In the central nervous system, NO play a key role on anxiety, depressive and compulsive related behaviors. Thus, the aim of the present study was evaluate whether the chronic or acute consumption of a high carbohydrate (HC) diet impair anxiety- and compulsivelike behaviors. Moreover, we also verified if the behavioral impairments induced by HC diet consumption are due to the exacerbation of NO synthesis. Male Balb/C mice received standard diet or HCD for 12 weeks (chronic protocol) or 3 days (acute protocol). The HCD was composed of 40% condensed milk, 40% chow diet, 12% refined sugar and 8% water. Initially, we observed that the chronic consumption of the HC diet did not impair the reinforcing effects induced by cocaine injection (15 mg/Kg) in the expression of the conditioning response in the Conditioning Place Preference Test. However, they displayed an impairment in the extinction of the conditioned response when compared to the control diet group. Moreover, the chronic, but not acute, consumption of HC diet induced a compulsive-like behavior in the Marble Burying Test, and anxiogenic-like behavior in the Novelty Suppressed Feeding test, and these effects were inhibited by Aminoguanidine (50 mg/Kg), a preferential inhibitor of iNOS. The behavioral effects observed in Marble Burying Test and Novelty Suppressed Feeding Test were positively correlated with an increase in nitrite levels in brain regions responsible for these behaviors, such as the prefrontal cortex, striatum and hippocampus (not significant in relation to the control diet group in Marble Burying test). Herein, Aminoguanidine also decreased significantly the nitrite levels in the striatum. Acute exposure to HC diet did not increase nitrite levels in these structures compared to the control diet group. In addition, chronic HC diet consumption increased iNOS levels, determined through the Western blotting analysis, in the striatum and prefrontal cortex, but not in the hippocampus as compared to control diet group. No difference between groups was observed to neuronal isoform (nNOS). Further, we also observedan increase in the activation or expression of microglial cells in these brain regions. Finally, glutamate release from striatal synaptosomes was higher in animalschronically fed with HC diet as compared to control diet group independently of calcium. These effects were not observed in animals acutely fed with HC diet. In conclusion, we suggest that chronic HC diet consumption induces compulsive-like behavior and increases stress vulnerability inducing anxiety-like behavior. It is possible suggest that the mechanisms underlying such effects resulted from activation of the microglial cells, which in turn increase the expression of iNOS, resulting in exacerbation of NO. As consequence, the NO facilitates the glutamatergic neurotransmission inducing the behavioral impairments.