Abstract
Metal ions such as iron, zinc, and manganese are essential to metabolic functions, protein synthesis, neurotransmission, and antioxidant neuroprotective mechanisms. Conversely, non-essential metals such as mercury and lead are sources of human intoxication due to occupational activities or environmental contamination. Essential or non-essential metal accumulation in the central nervous system (CNS) results in changes in blood-brain barrier (BBB) permeability, as well as triggering microglia activation and astrocyte reactivity and changing water transport through the cells, which could result in brain swelling. Aquaporin-4 is the main water channel in the CNS, is expressed in astrocyte foot processes in brain capillaries and along the circumventricular epithelium in the ventricles, and has important physiological functions in maintaining brain osmotic homeostasis and supporting brain excitability through regulation of the extracellular space. Some evidence has pointed to a role of AQP4 during metal intoxication in the brain, where it may act in a dual form as a neuroprotector or a mediator of the development of oxidative stress in neurons and astrocytes, resulting in brain swelling and neuronal damage. This mini-review presents the way some metal ions affect changes in AQP4 expression in the CNS and discuss the ways in which water transport in brain cells can be involved in brain damage.
Highlights
Frontiers in NeuroscienceToxins and Brain Aquaporin-4 Expression: An Overview. Front
Several metals, including zinc, iron, and manganese are important as major or trace elements in cellular biological functions, acting as catalytic cofactors of enzymes (Kress et al, 2002), cellular antioxidants, and neuromodulators (Paoletti et al, 1997)
The role of glial cells in protecting neuronal damage caused by metal ion accumulation in the brain has been studied, showing that astrocytes have a central role in reducing neural excitotoxicity by taking up metals that cross the blood-brain barrier (BBB) (Ni et al, 2011; Noguchi et al, 2013), while microglia release mediators of inflammatory and immune responses when activated by metal ions
Summary
Toxins and Brain Aquaporin-4 Expression: An Overview. Front. Some evidence has pointed to a role of AQP4 during metal intoxication in the brain, where it may act in a dual form as a neuroprotector or a mediator of the development of oxidative stress in neurons and astrocytes, resulting in brain swelling and neuronal damage. This mini-review presents the way some metal ions affect changes in AQP4 expression in the CNS and discuss the ways in which water transport in brain cells can be involved in brain damage
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