Early life overfeeding impairs spatial memory performance by reducing microglial sensitivity to learning

De Luca, S. N., Ziko, I., Sominsky, L., Nguyen, J. C.D., Dinan, T., Miller, A. A. , Jenkins, T. A. and Spencer, S. J. (2016) Early life overfeeding impairs spatial memory performance by reducing microglial sensitivity to learning. Journal of Neuroinflammation, 13(1), 112. (doi: 10.1186/s12974-016-0578-7) (PMID:27193330) (PMCID:PMC4872342)

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Abstract

Background: Obesity can lead to cognitive dysfunction including poor performance in memory tasks. However, poor memory is not seen in all obese humans and takes several months to develop in animal models, indicating the adult brain is relatively resistant to obesity’s cognitive effects. We have seen that, in the rat, overfeeding for as little as 3 weeks in early life leads to lasting obesity and microglial priming in the hypothalamus. Here we hypothesized that microglial hyper-sensitivity in the neonatally overfed rats extends beyond the hypothalamus into memory-associated brain regions, resulting in cognitive deficits. Methods: We tested this idea by manipulating Wistar rat litter sizes to suckle pups in litters of 4 (overfed) or 12 (control). Results: Neonatally overfed rats had microgliosis in the hippocampus after only 14 days overfeeding, and this persisted into adulthood. These changes were coupled with poor performance in radial arm maze and novel object recognition tests relative to controls. In controls, the experience of the radial arm maze reduced cell proliferation in the dentate gyrus and neuron numbers in the CA3. The learning task also suppressed microglial number and density in hippocampus and retrosplenial cortex. Neonatally overfed brains had impaired sensitivity to learning, with no neuronal or cell proliferative effects and less effective microglial suppression. Conclusions: Thus, early life overfeeding contributes to a long-term impairment in learning and memory with a likely role for microglia. These data may partially explain why some obese individuals display cognitive dysfunction and some do not, i.e. the early life dietary environment is likely to have a vital long-term contribution.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Miller, Dr Alyson
Authors: De Luca, S. N., Ziko, I., Sominsky, L., Nguyen, J. C.D., Dinan, T., Miller, A. A., Jenkins, T. A., and Spencer, S. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Neuroinflammation
Publisher:BioMed Central
ISSN:1742-2094
ISSN (Online):1742-2094
Copyright Holders:Copyright © 2016 De Luca et al.
First Published:First published in Journal of Neuroinflammation 13(1):112
Publisher Policy:Reproduced under a Creative Commons License

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