Elsevier

Neuroscience

Volume 112, Issue 4, 19 July 2002, Pages 803-814
Neuroscience

A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning

https://doi.org/10.1016/S0306-4522(02)00123-9Get rights and content

Abstract

We have investigated a potential mechanism by which a diet, similar in composition to the typical diet of most industrialized western societies rich in saturated fat and refined sugar (HFS), can influence brain structure and function via regulation of neurotrophins. We show that animals that learn a spatial memory task faster have more brain-derived neurotrophic factor (BDNF) mRNA and protein in the hippocampus. Two months on the HFS diet were sufficient to reduce hippocampal level of BDNF and spatial learning performance. Consequent to the action of BDNF on synaptic function, downstream effectors for the action of BDNF on synaptic plasticity were reduced proportionally to BDNF levels, in the hippocampus of rats maintained on the HFS diet between 2 and 24 months. In particular, animals maintained on the HFS diet showed a decrease in levels of: (i) synapsin I mRNA and protein (total and phosphorylated), important for neurotransmitter release; (ii) cyclic AMP-response element-binding protein (CREB) mRNA and protein (total and phosphorylated); CREB is required for various forms of memory and is under regulatory control of BDNF; (iii) growth-associated protein 43 mRNA, important for neurite outgrowth, neurotransmitter release, and learning and memory. Diet-related changes were specific for the hippocampus consequent to its role in memory formation, and did not involve neurotrophin-3, another member of the neurotrophin family.

Our results indicate that a popularly consumed diet can influence crucial aspects of neuronal and behavioral plasticity associated with the function of BDNF.

Section snippets

Animals and diets

The effect of different periods of HFS diet was assessed in female 2 month old Fisher 344 rats (Harlan Sprague Dawley, Inc., San Diego, CA, USA), maintained at 22–24°C in a 12:12 h light–dark cycle. We used female rats because they do not develop hypertension during the first year on a HFS diet (Roberts et al., 2000), and do not show atherosclerosis (Barnard et al., 1993). After acclimation of the animals for 1 week on standard rat chow, the rats were randomly assigned to a HFS diet or a

BDNF mRNA and protein

Levels of BDNF mRNA in the hippocampus of rodents fed a HFS diet were reduced compared to rodents fed a LFCC diet, between 2 and 24 months. The lowest BDNF mRNA values were achieved after 2 years (Fig. 1A). Decreases in BDNF mRNA in the HFS group were accompanied by a dramatic reduction in BDNF protein assessed after 6 months on the diet (Fig. 1B). Decreases in BDNF protein affected select hippocampal subfields, as histological analysis showed a qualitative reduction in BDNF immunostaining in

Discussion

The present study provides novel evidence on the effects of diet on neuronal plasticity and function via regulation of BDNF, in the absence of other risk factors associated to cardiovascular dysfunction. Spatial learning performance was associated with hippocampal levels of BDNF, such that animals with higher levels of BDNF performed better. Consuming a HFS diet decreased hippocampal BDNF mRNA and protein, and performance in the water maze. There were no alterations associated to the diet in

Acknowledgements

We thank V.R. Edgerton and J. Twiss for critical comments on the manuscript, and S. Vaynman for assistance with the Morris water maze testing. This study was supported by NIH awards NS 38978 and NS 39522.

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