The aging process is accompanied by critical changes in cellular and molecular functions, which upset the homeostatic balance in the central nervous system. Accumulation of metals renders the brain susceptible to neurotoxic insults by mechanisms such as mitochondrial dysfunction, neuronal calcium-ion dyshomeostasis, buildup of damaged molecules, compromised DNA repair, reduction in neurogenesis, and impaired energy metabolism. These hallmarks have been identified to be responsible for neuronal injuries, resulting in several neurological disorders. Various studies have shown solid associations between metal accumulation, abnormal protein expressions, and pathogenesis of neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and Amyotrophic lateral sclerosis. This review highlights metals (such as manganese, zinc, iron, copper, and nickel) for their accumulation, and consequences in the development of neurological disorders, in relation to the aging brain.

Overexposure of humans to heavy metals and essential metals poses a significant risk for the development of neurological and neurodevelopmental disorders. The mechanisms through which these metals exert their effects include the generation of reactive oxygen species, mitochondrial dysfunction, activation of inflammatory pathways, and disruption of cellular signaling. The function of glial cells in brain development and in the maintenance of homeostasis cannot be overlooked. The glial cells are particularly susceptible to metal-induced neurotoxicity. Accumulation of metals in the brain promotes microglial activation, triggering inflammatory responses that can coincide with other mechanisms of neurotoxicity, inducing alteration in synaptic transmission, cognitive deficit, and neuronal damage. In this review, we highlighted the role of glial dysfunction in some selected neurodegenerative diseases and neurodevelopmental disorders. We further dive into how exposure to metals such as nickel, manganese, methyl mercury, cadmium, iron, arsenic, and lead affect the functions of the microglia, astrocytes, and oligodendrocytes and the mechanisms through which they exert the effects on the brain in relation to some selected neurodegenerative diseases and neurodevelopmental disorders. Potential therapeutic interventions such as the use of new and improved chelating agents and antioxidant therapies might be a significant approach to alleviating these metal-induced glial perturbations.