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Relationships Between Essential Manganese Biology and Manganese Toxicity in Neurological Disease
Anna C Pfalzer1,2, Aaron B Bowman3,4,5
1Departments of Pediatrics, Vanderbilt University Medical Center (VUMC), Nashville, TN, USA.
Purpose Of Review:
Manganese (Mn) is critical for neurodevelopment but also has been implicated in the pathophysiology of several neurological diseases. We discuss how Mn requirements intersect with Mn biology and toxicity, and how these requirements may be altered in neurological disease. Furthermore, we discuss the emerging evidence that the level of Mn associated with optimal overall efficiency for Mn biology does not necessarily coincide with optimal cognitive outcomes.
Recent Findings:
Studies have linked Mn exposures with urea cycle metabolism and autophagy, with evidence that exposures typically neurotoxic may be able to correct deficiencies in these processes at least short term. The line between Mn-dependent biology and toxicity is thus blurred. Further, new work suggests that Mn exposures correlating to optimal cognitive scores in children are associated with cognitive decline in adults. This review explores relationships between Mn-dependent neurobiology and Mn-dependent neurotoxicity. We propose the hypothesis that Mn levels/exposures that are toxic to some biological processes are beneficial for other biological processes and influenced by developmental stage and disease state.
Insights
Manganese (Mn) is essential for brain development but can also cause neurological disease. Optimal Mn levels for biological function may not align with peak cognitive performance across different life stages.
Area of Science:
- Neuroscience
- Toxicology
- Developmental Biology
Background:
- Manganese (Mn) plays a crucial role in neurodevelopment.
- Mn is implicated in the pathology of various neurological disorders.
- The balance between Mn's biological necessity and its toxicity is complex.
Purpose of the Study:
- To review the intersection of Mn requirements, biology, and toxicity in neurological contexts.
- To explore how Mn requirements may change in the presence of neurological disease.
- To examine emerging evidence on Mn levels and cognitive outcomes.
Main Methods:
- Literature review of studies investigating manganese's role in neurodevelopment and neurological diseases.
- Analysis of research linking Mn exposure to metabolic pathways like urea cycle and autophagy.
- Synthesis of findings on Mn's impact on cognitive function across different age groups.
Main Results:
- Mn exposures linked to urea cycle metabolism and autophagy, with neurotoxic levels potentially correcting deficiencies short-term.
- The distinction between Mn-dependent biology and toxicity is not always clear.
- Mn levels associated with optimal childhood cognition may correlate with adult cognitive decline.
Conclusions:
- Mn levels that are toxic to certain biological processes may benefit others.
- The effects of Mn are influenced by developmental stage and disease state.
- Further research is needed to understand the dual role of Mn in neurobiology and neurotoxicity.