Abstract
The prevalence of cognitive decline is increasing as the ageing population is considerably growing. Restricting this age-associated process has become a challenging public health issue. The age-related increase in oxidative stress plays a major role in cognitive decline, because of its harmful effect on functional plasticity of the brain, such as long-term potentiation (LTP). Here, we show that citrulline (Cit) has powerful antioxidant properties that can limit ex vivo oxidative stress-induced LTP impairment in the hippocampus. We also illustrate that a three-month Cit supplementation has a protective effect on LTP in aged rats in vivo. The identification of a Cit oxidation byproduct in vitro suggests that the antioxidant properties of Cit could result from its own oxidation. Cit supplementation may be a promising preventive nutritional approach to limit age-related cognitive decline.
Highlights
Ageing is a time-related biological process frequently associated with physical and cognitive decline, possibly leading to pathological states
GSH/Total glutathione ratio has been assessed in control conditions (CTRL), after oxidative stress induced by H2O2 500 μM (H2O2), after H2O2 500 μM in the presence of Cit 5 mM (Cit 5 + H2O2) or Cit 10 mM (Cit 10 + H2O2)
The ratio observed under Cit + H2O2 conditions was not significantly different from that observed under control conditions (Cit 5 + H2O2 vs CTRL: ns; Cit 10 + H2O2 vs CTRL: ns)
Summary
Ageing is a time-related biological process frequently associated with physical and cognitive decline, possibly leading to pathological states. Ageing is associated with oxidative stress resulting from increased ROS production, because of mitochondrial dysfunction and decreased enzymatic and non-enzymatic antioxidant defense systems[5,6] This results in the accumulation of oxidatively damaged proteins, lipids, and DNA4, driving the impairment of various cell functions, such as mitochondrial and lysosomal function[7,8]. The strong association between ageing, oxidative damage in the brain, and cognitive functions suggests that oxidative stress and age-related cognitive decline are closely linked[10]. Synaptic plasticity, such as long term potentiation (LTP), defined as the long-lasting increase in the efficacy and strength of synaptic transmission of preexisting synapses, has been proposed to be an essential cellular process to encode memory[11]. Only a few studies have investigated the antioxidant effect of Cit in vivo and its positive effects against age-related disturbances[30,31], despite its known antioxidant properties described in a chemical system[26]
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