Fish oil promotes survival and protects against cognitive decline in severely undernourished mice by normalizing satiety signals

Abstract

Severe malnutrition resulting from anorexia nervosa or involuntary starvation leads to low weight, cognitive deficits, and increased mortality rates. In the present study, we examined whether fish oil supplementation, compared with canola oil, would ameliorate the morbidity and mortality associated with these conditions by normalizing endocannabinoid and monoaminergeric systems as well as other systems involved in satiety and cognitive function within the hypothalamus and hippocampus. Female Sabra mice restricted to 40% of their daily food intake exhibited decreased body weight, were sickly in appearance, displayed cognitive deficits, and had increased mortality rates. Strikingly, fish oil supplementation that contains high omega-3 fatty acids levels decreased mortality and morbidity, and normalized the expression of genes and neurotransmitters in the hippocampus and hypothalamus. Fish oil supplementation, but not canola oil, increased survival rates, improved general appearance, and prevented cognitive decline, despite the facts that both diets contained an equivalent number of calories and that there were no differences in weight between mice maintained on the two diets in 100% but decrease in the 40%. In the hypothalamus, the beneficial effects of fish oil supplementation were related to normalization of the endocannabinoid 2-arachidonylglycerol (2-AG), serotonin (5-HT) (p<0.056), dopamine (DA), neuropeptide Y (NPY), and Ca2+/calmodulin (CaM)-dependent protein kinase (Camkk2). In the hippocampus, fish oil supplementation normalized 5-HT, Camkk2, silent mating type information regulation 1 (SIRT-1), and brain-derived neurotrophic factor (BDNF). In conclusion, dietary supplements of fish oil, as source of omega-3 fatty acids, may alleviate cognitive impairments associated with severe diet restriction and prolong survival independently of weight gain by normalizing neurochemical systems.

A moderate diet restriction during pregnancy alters the levels of endocannabinoids and endocannabinoid-related lipids in the hypothalamus, hippocampus and olfactory bulb of rat offspring in a sex-specific manner

“…For instance, a decrease in the hippocampal 2-AG level has been correlated to anxiety-related responses [51, 75, 76], and the blockade of anandamide reuptake specifically in the hippocampus produces anxiolytic effects [77]. Furthermore, increased 2-AG in hippocampus was associated to mitigation of the cognitive alterations in severely undernourished mice supplemented with a diet rich in fish oil, an important source of n-3 PUFAs [78], although the opposite has been described in an animal model of schizophrenia [79]. In the context of nutritional programming, emotional responses and cognitive performance have been found to be affected after exposure to undernutrition during critical windows of development and/or in new born small for gestational age [14, 20, 80] and in a sex specific-manner [81, 82].…”

“…On the other hand, it is possible that some brain structures were protected from the effects of a moderate caloric restriction implemented only during pregnancy by the preferential uptake of the fetal tissues of specific LC-PUFAs, such as AA or n-3 PUFAs. It is interesting to note here that the n-3 PUFAs can affect the levels of endocannabinoids by decreasing their levels by competing for the metabolic enzymes [70, 84], or by increasing their levels depending on different circumstances [78, 85]. Additionally, the presence of sexual dimorphism mainly associated to the alterations found in olfactory bulb and the PEA levels in all the brain regions of females, suggest that the maternal calorie-restriction might have affected the male and female offspring through different mechanisms.…”

Omega-3 fatty acids improve psychomotor performance via mechanism not related to nitric acid production

“…[19] On the other hand, fish oil supplementation that contained high level of ω-3FAs prevented cognitive decline in mice, subjected to severe under-nutrition, via a mechanism involved normalisation of neurochemical systems in brain. [20] The effect of ω-3FAs in patients with decline cognitive function differed from that imposed on healthy subjects. In humans with mildmoderate Alzheimer's dementia, supplementation with docosahexaenoic acid (2g/d) for 18 months did not slow the rate of cognitive and functional decline.…”

Fatting the brain: a brief of recent research

“…More importantly, at post-ischemic stages, the subgranular zone in the dentate gyrus of the hippocampus, a niche of adult neurogenesis, displayed a concomitant increase in the neuronal expression of FABPs and the fatty acid receptor GPR40, representing compensatory processes of newborn cells (Boneva et al, 2011a,b; Yamashima, 2012). Finally, it is noteworthy that many of the beneficial actions of PUFAs on hippocampal function were associated with an increase in the production of BDNF, which is a member of the neurotrophin family of growth factors involved in supporting growth, differentiation and survival of neurons (Wu et al, 2008, 2011; Blondeau et al, 2009; Venna et al, 2009; Avraham et al, 2011; Vines et al, 2012). …”