Effects of Elevation of Brain Magnesium on Fear Conditioning, Fear Extinction, and Synaptic Plasticity in the Infralimbic Prefrontal Cortex and Lateral Amygdala

Abstract

Anxiety disorders, such as phobias and posttraumatic stress disorder, are among the most common mental disorders. Cognitive therapy helps in treating these disorders; however, many cases relapse or resist the therapy, which justifies the search for cognitive enhancers that might augment the efficacy of cognitive therapy. Studies suggest that enhancement of plasticity in certain brain regions such as the prefrontal cortex (PFC) and/or hippocampus might enhance the efficacy of cognitive therapy. We found that elevation of brain magnesium, by a novel magnesium compound [magnesium-L-threonate (MgT)], enhances synaptic plasticity in the hippocampus and learning and memory in rats. Here, we show that MgT treatment enhances retention of the extinction of fear memory, without enhancing, impairing, or erasing the original fear memory. We then explored the molecular basis of the effects of MgT treatment on fear memory and extinction. In intact animals, elevation of brain magnesium increased NMDA receptors (NMDARs) signaling, BDNF expression, density of presynaptic puncta, and synaptic plasticity in the PFC but, interestingly, not in the basolateral amygdala. In vitro, elevation of extracellular magnesium concentration increased synaptic NMDAR current and plasticity in the infralimbic PFC, but not in the lateral amygdala, suggesting a difference in their sensitivity to elevation of brain magnesium. The current study suggests that elevation of brain magnesium might be a novel approach for enhancing synaptic plasticity in a regional-specific manner leading to enhancing the efficacy of extinction without enhancing or impairing fear memory formation.

Synaptic function as a preclinical and experimental medicine readout for disease-modifying therapy in Alzheimer's Disease

“…Mechanistically, administration of MgT resulted in an increase in the number of presynaptic boutons, as well as postsynaptic NR2B-containing NMDA receptors, leading to an increase in hippocampal LTP. Elevation of brain Mg 2+ also increased NMDA receptor signaling and enhanced synaptic plasticity in the prefrontal cortex (PFC) but not in the lateral amygdala [64]. In parallel, MgT treated mice exhibited an increase in BDNF expression in the hippocampus and PFC, but not in amygdala [63,64].…”

Algorithm for the diagnosis, treatment, and prevention of stress (for general practitioners)

“…В последние годы в патогенезе стресса, когнитивных и эмо-циональных нарушений при связанных со стрессом расстрой-ствах активно обсуждается роль глутамата и N-метил-D-аспартат (NMDA)-рецепторов головного мозга [11], дисфункция которых приводит к повреждениям клеток глии и нейронов префронталь-ной коры, миндалины, гиппокампа и их связей с нижележащими структурами (таламусом, гипоталамусом, гипофизом, ретикуляр-ной формацией) [12][13].…”

Biodegradable magnesium nanoparticle-enhanced laser hyperthermia therapy

“…26 Another possibility is alkali-heat-treated magnesium (the magnesium is first immersed in supersaturated NaHCO 3 -MgCO 3 for 24 hours and then heat treated at 773 K for 10 hours), which may have an improved corrosion resistance. 23 In Qiao et al's study, alkali-treated magnesium caused distinct morphological changes in cells and a small hemolytic effect (2.2%), which is less than the allowable 5%. 24 Other useful surface modification methods to control the corrosion rate include micro arc oxidation, phosphating treatment, electrodepositing, and polymer coating.…”

“…22 Further, Abumaria et al's latest work suggests that elevation of brain magnesium might even be a novel approach for enhancing synaptic plasticity in a regional-specific manner leading to enhancement of extinction efficacy without enhancing or impairing fear memory formation. 23 Importantly, it is a kind of biodegradable material in the human body second to none compared with any other metal material. The standard electrode potential of magnesium is low, and it can be corrosively degraded and absorbed into the body in the presence of chloride ions in the physiological environment.…”