DHA diet reduces AD pathology in young APPswe/PS1ΔE9 transgenic mice: Possible gender effects

Abstract

Epidemiological and clinical trial findings suggest that consumption of docosahexaenoic acid (DHA) lowers the risk of Alzhemier’s disease (AD). We examined the effects of short-term (3 months) DHA enriched diet on plaque deposition and synaptic deficts in forebrain of young APPswe/PS1ΔE9 transgenic (tg) and non-transgenic (ntg) mice. Gas chromatography revealed a significant increase in DHA concomitant with a decrease of arachidonic acid in both brain and liver in mice fed with DHA. Female tg mice consumed relatively more food daily than ntg female mice, independent of diet. Plaque load was significantly reduced in the cortex, ventral hippocampus and striatum of female APPswe/PS1ΔE9 tg mice on DHA diet compared to female tg mice on control diet. LR11 levels were unchanged in mice on DHA. Moreover drebrin levels were significantly increased in the hippocampus of tg mice on the DHA diet. Finally, in vitro DHA treatment prevented amyloid toxicity in cell cultures. Our findings support the concept that increased DHA consumption may play and important role in preventing brain insults in AD.

Omega-3 Fatty Acids Augment the Actions of Nuclear Receptor Agonists in a Mouse Model of Alzheimer's Disease

“…3A). These effects in the 5XFAD mouse are consistent with previous literature reporting that AD mouse models supplemented with DHA-enriched diets displayed decreased plaque burden (Lim et al, 2005;Perez et al, 2010). While there are several key differences between the other studies and ours, we postulate that provision of DHA as a free fatty acid delivered by oral gavage in our study, either alone, and in combination with bexarotene, may promote clearance of dense-core plaques by catalyzing target genes of LXR and PPAR␥ involved in phagocytosis (Terwel et al, 2011;Yamanaka et al, 2012).…”

“…Importantly, DHA also acts as a nuclear receptor agonist that activates the nuclear receptors RXR (de Urquiza et al, 2000;Lengqvist et al, 2004) and PPAR␥ (Calder, 2015). Significantly, dietary supplementation with DHA has been effective at decreasing AD-related pathology and behavioral deficits in mouse models (Lim et al, 2005;Perez et al, 2010). DHA also exerts anti-inflammatory effects through activation of PPARs (Wahli and Michalik, 2012;Calder, 2015).…”

The proof-of-concept of ASS234: Peripherally administered ASS234 enters the central nervous system and reduces pathology in a male mouse model of Alzheimer disease

“…31 These differences might be associated with age and duration of treatment, as previously reported. 52 According to the amyloid cascade hypothesis, Aβ peptide accumulates into plaques, triggering a series of events lead ing to dementia. 1 However, this theory fails to explain the discrepancy between amyloid plaque deposition and cogni tive impairment in patients with Alzheimer disease.…”

Transgenic conversion of omega-6 into omega-3 fatty acids in a mouse model of Parkinson's disease

“…Synaptic markers, synaptophysin as well as the synaptosomal-associated protein (SNAP-25) and the postsynaptic density marker (PSD-95) were also analyzed by immuno- note, mice were carefully genotyped twice in order to distinguish transgenic mice from NonTg littermates, an approach also used by other research groups ( 19,33,34 ), whereas other authors have relied exclusively on phenotyping the animal with the fatty acid profi les ( 20 ). As reported by our group ( 4,35 ) and more recently by several other research teams ( 34,36 ), dietary DHA supplementation readily increases n -3:n -6 PUFA ratio over 1.5. This effect is much more signifi cant than with fat-1 transgene as reported previously ( 33,34 ) and substantiated by our data.…”