Elsevier

Neuroscience

Volume 119, Issue 2, 27 June 2003, Pages 365-375
Neuroscience

Cellular
A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain-derived neurotrophic factor

https://doi.org/10.1016/S0306-4522(03)00154-4Get rights and content

Abstract

We have conducted studies to determine the potential of dietary factors to affect the capacity of the brain to compensate for insult. Rats were fed with a high-fat sucrose (HFS) diet, a popularly consumed diet in industrialized western societies, for 4 weeks before a mild fluid percussion injury (FPI) or sham surgery was performed. FPI impaired spatial learning capacity in the Morris water maze, and these effects were aggravated by previous exposure of the rats to the action of the HFS diet. Learning performance decreased according to levels of brain-derived neurotrophic factor (BDNF) in individual rats, such that rats with the worst learning efficacy showed the lowest levels of BDNF in the hippocampus. BDNF immunohistochemistry localized the decreases in BDNF to the CA3 and dentate gyrus of the hippocampal formation. BDNF has a strong effect on synaptic plasticity via the action of synapsin I and cAMP-response element-binding protein (CREB), therefore, we assessed changes in synapsin I and CREB in conjunction with BDNF. Levels of synapsin I and CREB decreased in relation to decreases in BDNF levels. The combination of FPI and the HFS diet had more dramatic effects on the active state (phosphorylated) of synapsin I and CREB. There were no signs of neurodegeneration in the hippocampus of any rat group assessed with Fluoro-Jade B staining. The results suggest that FPI and diet impose a risk factor to the molecular machinery in charge of maintaining neuronal function under homeostatic and challenging situations.

Section snippets

Experimental design and tissue preparation

Eighty male Sprague–Dawley rats (Charles River Laboratories, Inc., Wilmington, MA) weighing between 200 and 240 g were housed in cages (two rats per cage) and maintained in environmentally controlled rooms (22–24 °C) with a 12 h light/dark cycle. After acclimatization for 1 week on standard rat chow, the rats were randomly assigned to HFS diet or regular diet (RD) for 4 weeks. The diets, fed ad libitum, were provided in powder (TestDiet Inc., Richmond, IN) in large bowl and contained a standard

Spatial learning

Animals were maintained on HFS diet or RD for 4 weeks and some of them received a FPI and were killed 1 week later. We performed the Morris water maze test daily for three consecutive days before and after FPI to assess spatial memory function. The escape latency to find the platform was about the same in HFS versus RD intact rats (Fig. 1A). FPI resulted in longer escape latencies in RD and HFS rats compared with animals receiving sham surgery, and the latency of HFS rats was longer than that

Discussion

Current results demonstrate that FPI significantly impaired learning and memory performance in rats. Moreover, consumption of a HFS diet for 1 month before the injury, potentiated the deleterious effects of FPI on cognitive function and neuronal plasticity. BDNF and its downstream effectors on synaptic plasticity, synapsin I and CREB, appear to be involved with the effects of the HFS diet. The HFS diet and trauma reduce levels of CREB and synapsin I and the efficiency of crucial molecular

Acknowledgements

We thank Dr. Grace Griesbach for help with the TBI experiments. This study was supported by awards from the Alzheimer’s Association, the UCLA Brain Injury Research Center, and NIH (NINDS 38978 and 39522).

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