Brain free magnesium homeostasis as a target for reducing cognitive aging

Excerpt

In the general deterioration of physiological functions that takes place in aging, the prevalence of cognitive impairments, and particularly of those related to learning and memory, makes these deficits a major concern of public health. Although the exact nature of cellular and molecular substrates underlying learning and memory still remains an open issue for the neurobiologist, the current hypothesis assumes that it is determined by the capacity of brain neuronal networks to express short- and long-term changes in synaptic strength. Accordingly, the capacity of functional plasticity is impaired in the brain of aged memory-deficient animals. Short-term changes in synaptic transmission closely depend on transmitter release and neuronal excitability while long-term modifications are mainly related to the activation of the N-methyl-D-aspartate receptor (NMDA-R), a subtype of glutamate receptors. Because transmitter release, neuronal excitability and NMDA-R activation are modulated by magnesium (Mg²⁺), a change in brain Mg²⁺ homeostasis could affect synaptic strength and plasticity in neuronal networks and consequently could alter memory capacities. In addition, alteration of brain Mg²⁺ levels could be regarded as a possible mechanism contributing to cognitive aging. According to these postulates, long-term increase in Mg²⁺ levels facilitates the conversion of synapses to a plastic state while learning and memory capacities are enhanced in adult animals fed with a diet enriched in Mg²⁺-L-threonate, a treatment that significantly elevates brain Mg²⁺ levels. Because Mg²⁺-L-threonate also improves learning and memory in aged animals, the regulation of brain Mg²⁺ homeostasis may therefore be regarded as a relevant target for the development of new pharmacological strategies aimed at minimizing cognitive aging.