Early-life overnutrition influences spatial memory and hippocampal microgliosis

Abstract

The early life nutritional environment can program hypothalamic microglial proliferation, with a predisposition to a central proinflammatory profile long-term. We hypothesise that long-term microgliosis caused by overnutrition during critical developmental periods extend beyond the hypothalamus into the hippocampus, a pivotal region in memory formation, and that this will disrupt cognition. To test this idea, we manipulated the litter sizes Wistar rat pups were suckled in, ensuring that the pups were raised in litters of 4 (neonatally overfed) or 12 (control). This model of manipulation produces long-term obesity as well as microglial priming in the hypothalamus in the neonatally overfed. Once the rats reached adulthood, we observed the effects of early life overfeeding on cognitive function using the radial arm maze to investigate rat spatial learning and memory. We also examined hippocampal microglial number and density using immunohistochemistry for ionized calcium binding protein (Iba1). Adult rats that were overfed as neonates did not consolidate spatial working and reference memory as efficiently as their control counterparts, despite reaching criterion at the same time. This was accompanied by microgliosis in the dentate gyrus of the hippocampus in the neonatally overfed. These findings suggest early-life diet may influence spatial memory formation at the level of the hippocampus.