There is accumulating evidence showing that lifestyle factors like diet may influence the onset and progression of Alzheimer’s disease (AD). Our previous studies suggest that a multi-nutrient diet, Fortasyn, containing nutritional precursors and cofactors for membrane synthesis, viz. docosahexaenoic acid, eicosapentaenoic acid, uridine-mono-phosphate, choline, phospholipids, folic acid, vitamins B6, B12, C, E, and selenium, has an ameliorating effect on cognitive deficits in an AD mouse model. In the present study we analyzed learning strategies and memory of 11-month-old AβPPswe/PS1dE9 (AβPP/PS1) mice in the Morris water maze (MWM) task performed after nine months of dietary intervention with a control diet or a Fortasyn diet to characterize diet-induced changes in cognitive performance. The Fortasyn diet had no significant effect on MWM task acquisition.
To assess hippocampus-dependent learning, the strategies that the mice used to find the hidden platform in the MWM were analyzed using the swim path data. During the fourth day of the MWM, AβPP/PS1 mice on control diet more often used the non-spatial random search strategy, while on the Fortasyn diet, the transgenic animals exhibited more chaining strategy than their wild-type littermates. During the probe trial, AβPP/PS1 mice displayed no clear preference for the target quadrant. Notably, in both transgenic and nontransgenic mice on Fortasyn diet, the latency to reach the former platform position was decreased compared to mice on the control diet. In conclusion, this specific nutrient combination showed a tendency to improve searching behavior in AβPP/PS1 mice by increasing the use of a more efficient search strategy and improving their swim efficiency by decreasing the latency to reach the former platform position.
Researchers have devised several lipid-based diets aimed at slowing down progression and relieving symptoms of Alzheimer’s disease.
Alzheimer´s disease (AD) is the most common disease underlying memory problems and dementia in the elderly. One of the invariable pathologies in AD is degeneration of cholinergic synapses in brain cortex and hippocampus. Despite enormous effort to find out an efficient treatment, current pharmacological interventions are limited to a few drugs that alleviate symptoms but do not slow down the underlying disease processes. These drugs include inhibitors of cholinesterases, enzymes that degrade the neurotransmitter acetylcholine, or memantine, a modulator of glutamate neurotransmission.
It is generally accepted that lifestyle and particularly dietary habits influence mental health, and prevalence and progression of AD. Numerous epidemiological studies have revealed profitable effects of dietary intake of especially fish oil on cognitive decline during aging and dementia.
Within the EU-funded project LipiDiDiet (FP7-211696), therapeutic and preventive impact of nutritional lipids on neuronal and cognitive performance in aging, Alzheimer´s disease and vascular dementia, researchers devised several lipid-based diets aimed at slowing down progression and relieving symptoms of AD. Short-term (3 weeks) feeding of young adult APPswe/PS1dE9 mice (transgenic mouse model of AD) with experimental diets containing fish oil or stigmasterol reversed the decrease in responsiveness of hippocampal muscarinic receptors to acetylcholine compared to their non-transgenic littermates. Only fish oil based diet enriched with nutrients supporting neuroprotection (Fortasyn diet) increased in addition the density of muscarinic receptors and cholinergic synapses in the hippocampus.
These findings yield important proof-of-principle evidence that regular intake of specific dietary components may help to prevent some of the key early functional changes that take place in the Alzheimer brain. These findings support viability of the dietary approach in AD.
Source: Faizan ul Haq – Bentham Science Publishers
Image Source: Image is in the public domain
Original Research: Abstract for “Lipid-Based Diets Improve Muscarinic Neurotransmission in the Hippocampus of Transgenic APPswe/PS1dE9 Mice” by Helena Janickova, Vladimir Rudajev, Eva Dolejsi, Hennariikka Koivisto, Jan Jakubik, Heikki Tanila, Esam E. El-Fakahany and Vladimir Dolezal in Current Alzheimer Research. Published online February 2016 doi:10.2174/1567205012666151027130350
Lipid-Based Diets Improve Muscarinic Neurotransmission in the Hippocampus of Transgenic APPswe/PS1dE9 Mice
Transgenic APPswe/PS1dE9 mice modeling Alzheimer’s disease demonstrate ongoing accumulation of β-amyloid fragments resulting in formation of amyloid plaques that starts at the age of 4-5 months. Buildup of β-amyloid fragments is accompanied by impairment of muscarinic transmission that becomes detectable at this age, well before the appearance of cognitive deficits that manifest around the age of 12 months. We have recently demonstrated that long-term feeding of trangenic mice with specific isocaloric fish oil-based diets improves specific behavioral parameters. Now we report on the influence of short-term feeding (3 weeks) of three isocaloric diets supplemented with Fortasyn (containing fish oil and ingredients supporting membrane renewal), the plant sterol stigmasterol together with fish oil, and stigmasterol alone on markers of cholinergic neurotransmission in the hippocampus of 5-month-old transgenic mice and their wild-type littermates. Transgenic mice fed normal diet demostrated increase in ChAT activity and attenuation of carbachol-stimulated GTP-γ35S binding compared to wild-type mice. None of the tested diets compared to control diet influenced the activities of ChAT, AChE, BuChE, muscarinic receptor density or carbachol-stimulated GTP-γ35S binding in wild-type mice. In contrast, all experimental diets increased the potency of carbachol in stimulating GTP-γ35S binding in trangenic mice to the level found in wild-type animals. Only the Fortasyn diet increased markers of cholinergic synapses in transgenic mice. Our data demonstrate that even short-term feeding of transgenic mice with chow containing specific lipid-based dietary supplements can influence markers of cholinergic synapses and rectify impaired muscarinic signal transduction that develops in transgenic mice.
“Lipid-Based Diets Improve Muscarinic Neurotransmission in the Hippocampus of Transgenic APPswe/PS1dE9 Mice” by Helena Janickova, Vladimir Rudajev, Eva Dolejsi, Hennariikka Koivisto, Jan Jakubik, Heikki Tanila, Esam E. El-Fakahany and Vladimir Dolezal in Current Alzheimer Research. Published online February 2016 doi:10.2174/1567205012666151027130350