Avaliação crônica de aspectos neuroinflamatórios, cognitivos e de memória em modelo murino tratado com dieta hiperpalatável

Abstract

Excessive consumption of hyperpalatable and hypercaloric food has been pointed out as a factor associated with cognitive decline and memory impairment in obesity. In this context, it is known that the integration between peripheral-central inflammation may act as an important catalyst for the negative impacts of obesity on memory, especially in key areas which are vulnerable to nutritional stress, such as the hippocampus. However, little is known about how the inflammatory state generated by obesity may impact specific neurotransmission systems associated with memory regulation, such as the glutamatergic system. Here, we tested the hypothesis that chronic obesity exposure to a highly palatable diet in a murine model may induce neuroinflammation, glutamatergic dysfunction, and memory impairment. For that, we exposed 3-4 weeks old C57BL/6J male mice to an isocaloric or a high sugar and butter diet (HSB) for 12 weeks. Behavioral tests, hippocampal and serum proinflammatory cytokines pattern, blood-brain barrier permeability proteins, as well the levels of glutamate, glutamatergic receptors, neurotrophic factors and fractalkine-CX3CR1 axis were evaluated. Our results showed that chronic consumption of the HSB diet was able to promote metabolic dysfunction, increasing the hippocampal glutamate levels, as well as inducing a decrease in memory reconsolidation and extinction. Although our data indicated a peripheral pro-inflammatory profile, we did not observe neuroinflammatory features in our model, suggesting that the establishment of glutamatergic dysfunction appears to be independent of inflammation, and likely modulated by metabolic dysfunctions. Interestingly, we also observed that the HSB diet also increased hippocampal fractalkine levels, a key chemokine associated with neuroprotection and pro-inflammatory conditions. Then, we hypothesized that increased glutamate levels may saturate synaptic communication, partially limiting plasticity, and that increased levels of fractalkine could be a strategy to decrease glutamatergic damage. However, we also speculate that in the long term, this mechanism may predispose to a neuroinflammatory environment.