Cognition and Synaptic-Plasticity Related Changes in Aged Rats Supplemented with 8- and 10-Carbon Medium Chain Triglycerides.

Dongmei Wang,Ellen S Mitchell,Yael Abreu-Villaça

doi:10.1371/journal.pone.0160159

Abstract

Brain glucose hypometabolism is a common feature of Alzheimer’s disease (AD). Previous studies have shown that cognition is improved by providing AD patients with an alternate energy source: ketones derived from either ketogenic diet or supplementation with medium chain triglycerides (MCT). Recently, data on the neuroprotective capacity of MCT-derived medium chain fatty acids (MCFA) suggest 8-carbon and 10-carbon MCFA may have cognition-enhancing properties which are not related to ketone production. We investigated the effect of 8 week treatment with MCT8, MCT10 or sunflower oil supplementation (5% by weight of chow diet) in 21 month old Wistar rats. Both MCT diets increased ketones plasma similarly compared to control diet, but MCT diets did not increase ketones in the brain. Treatment with MCT10, but not MCT8, significantly improved novel object recognition memory compared to control diet, while social recognition increased in both MCT groups. MCT8 and MCT10 diets decreased weight compared to control diet, where MCFA plasma levels were higher in MCT10 groups than in MCT8 groups. Both MCT diets increased IRS-1 (612) phosphorylation and decreased S6K phosphorylation (240/244) but only MCT10 increased Akt phosphorylation (473). MCT8 supplementation increased synaptophysin, but not PSD-95, in contrast MCT10 had no effect on either synaptic marker. Expression of Ube3a, which controls synaptic stability, was increased by both MCT diets. Cortex transcription via qPCR showed that immediate early genes related to synaptic plasticity (arc, plk3, junb, egr2, nr4a1) were downregulated by both MCT diets while MCT8 additionally down-regulated fosb and egr1 but upregulated grin1 and gba2. These results demonstrate that treatment of 8- and 10-carbon length MCTs in aged rats have slight differential effects on synaptic stability, protein synthesis and behavior that may be independent of brain ketone levels.

Highlights

Octanoic acid, and decanoic acid, 8-carbon and 10-carbon medium chain fatty acids (MCFA), respectively, are found as medium chain triglycerides (MCT) in foods such as coconut oil and PLOS ONE | DOI:10.1371/journal.pone.0160159 August 12, 2016Medium Chain Triglycerides Improve Memory in Aged Rats goat milk
The diet appeared to be well-tolerated by all groups, due to the extreme age of the animals 3 animals died in the last week of the intervention: 1 mortality in the control group and 2 mortalities in the MCT8 group
Plasma beta-hydroxybutyrate (BHB) as measured by colorimetric kits increased in the MCT10- and MCT8-treated group compared to controls (Fig 1B), yet brain BHB as measured by GC-MS were similar in all groups (Fig 1C)

Summary

Introduction

Decanoic acid, 8-carbon and 10-carbon medium chain fatty acids (MCFA), respectively, are found as medium chain triglycerides (MCT) in foods such as coconut oil and PLOS ONE | DOI:10.1371/journal.pone.0160159 August 12, 2016Medium Chain Triglycerides Improve Memory in Aged Rats goat milk. Ketones act as substrates for production of acetyl-CoA, they can serve as alternative energy sources when glucose is low [2]. This glycolysis bypass property of ketones is especially important for neurons, which use glucose or ketones as primary energy sources for production of ATP. Alzheimer’s disease (AD) patients have been shown to exhibit decreases in brain glucose metabolism and glycolytic enzymes, ketones may be useful as an adjuvant fuel [3]. Recent research has shown that ketones derived from medium chain fatty acids improve cognition in diabetic and AD patients, and attenuate neurodegeneration in an ALS mouse model [4]

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