Modulatory role of α-MSH in hippocampal-dependent memory impairment, synaptic plasticity changes, oxidative stress, and astrocyte reactivity induced by short-term high-fat diet intake

High-fat diet (HFD) consumption is associated with cognitive deficits and neurodegenerative diseases. Since the hippocampus is extremely sensitive to pathophysiological changes, neuroinflammation and the concomitant oxidative stress induced by HFD can significantly interfere with hippocampal-dependent functions related to learning and memory. The neuropeptide alpha-melanocyte stimulating hormone (α-MSH) mediates neuroprotective actions in the central nervous system and can reverse the effects of neuroinflammation in cognitive functions that depend on the hippocampus. In this study, we used male Wistar rats to evaluate the effect of short-term HFD intake (5 days) plus a mild immune challenge, Lipopolysaccharide (LPS 10 μg/kg) on contextual fear, changes in structural plasticity, oxidative stress, and astrocyte reactivation in the hippocampus. We also determined the possible modulatory role of α-MSH. HFD consumption was associated with an increase in markers of oxidative stress (Advanced oxidation protein products and Malondialdehyde) in the dorsal hippocampus (DH). We also found changes in hippocampal structural synaptic plasticity, observing a decrease in total spine in the DH after HFD plus LPS. We observed astrocyte proliferation and a significant increase in the percentage of the area occupied by GFAP. Treatment with α-MSH (0.1 μg/0.25 μl) in the DH reversed the effect of short-term HFD plus LPS on contextual fear memory, oxidative stress, and spine density. α-MSH also reduced astrocyte proliferation. Our present results indicate that HFD consumption for a short period sensitizes the central nervous system (CNS) to a subsequent immune challenge and impairs contextual fear memory and that α-MSH could have a modulatory protective effect.