Comportamentos de ansiedade e compulsão em camundongos observados após consumo de dieta rica em carboidratos são associados à inflamação central e periférica

Abstract

Excessive intake of ultra-processed foods promotes the prejudicial expansion of adipose tissue leading to the development of obesity. Consequently, occur the development of a low-grade chronic inflammatory response. This process is not limited to the periphery and also affects the central nervous system. Inflammatory factors are commonly associated with psychiatric disorders like anxiety and obsessive-compulsive disorder. Indeed, our previous data described anxiogenic-like and compulsive behavior after chronic consumption of a high-carbohydrate (HC) diet in mice. These effects were associated with an increase of inflammatory processes in brain regions involved in such behaviors. The minocycline has anti-inflammatory and has been investigated as a new pharmacological tool for treating neuropsychiatric diseases. Moreover, the replacement of obesogenic diet induces weight loss and has anti inflammatory properties, and has anxiolytic and antidepressant effects in rodents. The objective of our study was to verify whether the treatment with minocycline or diet intervention would be effective in attenuating the central and peripheric inflammatory processes, as well as the behaviors of compulsion and anxiety observed after the consumption of HC diet in mice. Male Balb-C mice received the standard diet or HC for 4, 8, and 12 weeks and were subjected to the marble-burying test (MB). Mice fed with 12 weeks of HC diet treated with minocycline for 7 or 15 daily injections (50mg/kg). Twenty-four hours after the last injection, they were subjected to the MB and Novelty Suppressed Feed test (NSF). The brain, adipose tissues, and serum were removed for immunohistochemical and biochemical analyzes. Finally, the effect of replacing the HC diet with a standard diet for 15 days in the MB and NSF tests was evaluated. Only the 12-week diet consumption induced compulsive-like behavior in the MB test. The minocycline administered for 15 days reversed the compulsive and anxious behaviors and several parameters of microglial activation in the prefrontal cortex and hippocampus. The effects of minocycline were not related to body adiposity and the levels of serum metabolic, adipocytokines, and cytokines on adipose tissue. Finally, replacing the HC diet with the standard diet for 15 days reduced the body adiposity and anxious-like behavior but did not reverse the compulsive behavior. In conclusion, the HC diet requires prolonged consumption to promote compulsive behavior. Additionally, the results obtained after minocycline treatment reinforce the role of neuroinflammation in behavior changes promoted by chronic consumption of the HC diet. Further, the diet intervention did not reduce the compulsive-like behavior since it partially attenuated the peripheral metabolic parameters induced by HC diet consumption.