Abstract
As major components of neuronal membranes, omega-3 polyunsaturated acids (n-3 PUFA) exhibit a wide range of regulatory functions, modulating from synaptic plasticity to neuroinflammation, from oxidative stress to neuroprotection. Recent human and animal studies indicated the n-3 PUFA neuroprotective properties in aging, with a clear negative correlation between n-3 PUFA levels and hippocampal deficits. The present multidimensional study was aimed at associating cognition, hippocampal neurogenesis, volume, neurodegeneration and metabolic correlates to verify n-3 PUFA neuroprotective effects in aging. To this aim 19 month-old mice were given n-3 PUFA mixture, or olive oil or no dietary supplement for 8 weeks during which hippocampal-dependent mnesic functions were tested. At the end of behavioral testing morphological and metabolic correlates were analyzed. n-3 PUFA supplemented aged mice exhibited better object recognition memory, spatial and localizatory memory, and aversive response retention, without modifications in anxiety levels in comparison to controls. These improved hippocampal cognitive functions occurred in the context of an enhanced cellular plasticity and a reduced neurodegeneration. In fact, n-3 PUFA supplementation increased hippocampal neurogenesis and dendritic arborization of newborn neurons, volume, neuronal density and microglial cell number, while it decreased apoptosis, astrocytosis and lipofuscin accumulation in the hippocampus. The increased levels of some metabolic correlates (blood Acetyl-L-Carnitine and brain n-3 PUFA concentrations) found in n-3 PUFA supplemented mice also pointed toward an effective neuroprotection. On the basis of the present results n-3 PUFA supplementation appears to be a useful tool in health promotion and cognitive decline prevention during aging.
Highlights
The rise of life expectancy has amplified the interest in the prevention and improvement of age-related brain dysfunctions
Animals were divided in three groups: (1) mice supplemented with an n-3 PUFA mixture (440 mg/kg) by daily gavage for 8 weeks (5 day/week) (Group name: n-3 PUFA; n = 12); (2) mice supplemented with olive oil (440 mg/kg) by daily gavage for the same period used as controls of an iso-caloric intake, as reported in previous studies (Kotani et al, 2006; Oarada et al, 2008; Nakamoto et al, 2010; Sinn et al, 2010; Danthiir et al, 2011; Vinot et al, 2011) (Group name: OLIVE OIL; n = 13); (3) no supplemented mice used as controls of eventual forced feeding effects (Group name: NAÏVE; n = 12) (Figure 1)
The present data consistently demonstrate the beneficial effects of n-3 PUFA supplementation on hippocampal resilience to aging
Summary
The rise of life expectancy has amplified the interest in the prevention and improvement of age-related brain dysfunctions. Agerelated cognitive decline is due to a progressive impairment of the underlying brain cell processes due to neuroinflammation, oxidative stress, reduced synaptic plasticity and neurogenesis, leading to a consequent and irreversible neuronal loss of gray and white matter volume (Driscoll et al, 2006; Masliah et al, 2006; Brown, 2009). Nutritional research indicates that Western diets do not provide the aged brain with an optimal supply of omega-3 polyunsaturated fatty acids (n-3 PUFA) (Woo, 2011). Aging is associated to reduced cerebral n-3 PUFA levels due to reduced absorption, reduced n-3 PUFA capacity to cross the blood-brain barrier, reduced capacity to convert shorter chained fatty acids to longer fatty acids, and increased oxidative stress (Yehuda, 2012)
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