Magnesium Is a Key Player in Neuronal Maturation and Neuropathology

Abstract

Magnesium (Mg) is the second most abundant cation in mammalian cells, and it is essential for numerous cellular processes including enzymatic reactions, ion channel functions, metabolic cycles, cellular signaling, and DNA/RNA stabilities. Because of the versatile and universal nature of Mg2+, the homeostasis of intracellular Mg2+ is physiologically linked to growth, proliferation, differentiation, energy metabolism, and death of cells. On the cellular and tissue levels, maintaining Mg2+ within optimal levels according to the biological context, such as cell types, developmental stages, extracellular environments, and pathophysiological conditions, is crucial for development, normal functions, and diseases. Hence, Mg2+ is pathologically involved in cancers, diabetes, and neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, and demyelination. In the research field regarding the roles and mechanisms of Mg2+ regulation, numerous controversies caused by its versatility and complexity still exist. As Mg2+, at least, plays critical roles in neuronal development, healthy normal functions, and diseases, appropriate Mg2+ supplementation exhibits neurotrophic effects in a majority of cases. Hence, the control of Mg2+ homeostasis can be a candidate for therapeutic targets in neuronal diseases. In this review, recent results regarding the roles of intracellular Mg2+ and its regulatory system in determining the cell phenotype, fate, and diseases in the nervous system are summarized, and an overview of the comprehensive roles of Mg2+ is provided.

Magnesium Status in Children with Attention-Deficit/Hyperactivity Disorder and/or Autism Spectrum Disorder

“…Mg is considered as an important player in neurodevelopment and neuronal maturation [13] and may modulate the pathogenetic mechanisms of both ADHD and ASD development. Particularly, Mg treatment can reduce neuroinflammation [27] and excitotoxicity [28].…”

“…It may also interact with dopamine signaling, thus providing a link between Mg status and ADHD [29]. Moreover, adequate Mg levels support plasticity and interconnectivity [13].…”

“…Magnesium (Mg) is an essential element for child growth, and the recommended daily allowances for children aged 1-3, 4-8, and 9-13 years old are estimated at 80, 130, and 240 mg, respectively. Mg regulation occurs through a balance between absorption, excretion, and redistribution from bones, and the element is involved in multiple processes [12] including brain development and functioning [13]. Multiple studies have assessed Mg status in ADHD, although with conflicting results at times [14,15].…”

General Aspects of Metal Ions as Signaling Agents in Health and Disease

“…Moreover, cytosolic magnesium regulates the signaling activities of extracellular signal-regulated kinase (ERK) negatively, cyclic AMP response element binding protein (CREB) positively, and mammalian target of rapamycin (mTOR) sigmoidally [ 63 ]. As these intracellular signaling pathways regulate neuronal growth and differentiation, magnesium, by activating CREB and mTOR signaling, enhances the maturation of neural networks [ 64 ].…”

“…As a result of the contradictory observations regarding magnesium, its regulatory system and the roles of intracellular Mg 2+ are controversial [ 64 ].…”