| dc.description.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. | |
