Cognitive deficit and neurodegenerative diseases are associated with age, however environmental factors such as chronic consumption of a high-fat diet (HFD) aggravate them in young and adults. The effects of HFD on the central nervous system (CNS) could be related to neuroinflammation, and even the consumption of HFD for a short period of time can exacerbate the inflammatory response to a mild immune challenge. Alpha-melanocyte stimulating hormone (α-MSH) mediates antiinflammatory and neuroprotective actions. We explored whether short-term (5 days) HFD consumption plus a mild immune challenge (LPS 10µg/Kg), potentiated the neuroinflammatory response in the hippocampus leading to cognitive deficits and possible changes in hippocampal structural plasticity. Our results show that short-term HFD does not affect body weight, however, produces changes in total cholesterol. HFD impaired contextual fear (hippocampal dependent) memory in rats that received LPS. This effect was associated with a decrease in spine density in the dorsal hippocampus (DH). The treatment with α-MSH (0.1µg/0.25µl) in the DH reversed the effect of short-term HFD in both contextual fear memory and in spine density.
Our present results indicate that HFD consumption for a short period sensitizes CNS to a subsequent immune challenge and produces impairment in the contextual fear memory that could be related to changes in hippocampal structural plasticity. α-MSH could have a protective effect.