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      Multilevel Impacts of Iron in the Brain: The Cross Talk between Neurophysiological Mechanisms, Cognition, and Social Behavior

      review-article
      1 , 2 , 3 , *
      Pharmaceuticals
      MDPI
      iron, brain, neurophysiology, cognition, social behavior

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          Abstract

          Iron is a critical element for most organisms, which plays a fundamental role in the great majority of physiological processes. So much so, that disruption of iron homeostasis has severe multi-organ impacts with the brain being particularly sensitive to such modifications. More specifically, disruption of iron homeostasis in the brain can affect neurophysiological mechanisms, cognition, and social behavior, which eventually contributes to the development of a diverse set of neuro-pathologies. This article starts by exploring the mechanisms of iron action in the brain and follows with a discussion on cognitive and behavioral implications of iron deficiency and overload and how these are framed by the social context. Subsequently, we scrutinize the implications of the disruption of iron homeostasis for the onset and progression of psychosocial disorders. Lastly, we discuss the links between biological, psychological, and social dimensions and outline potential avenues of research. The study of these interactions could ultimately contribute to a broader understanding of how individuals think and act under physiological and pathophysiological conditions.

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          Most cited references151

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          Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy

          Autophagy, the process by which proteins and organelles are sequestered in double-membrane structures called autophagosomes and delivered to lysosomes for degradation, is critical in diseases such as cancer and neurodegeneration 1,2 . Much of our understanding of this process has emerged from analysis of bulk cytoplasmic autophagy, but our understanding of how specific cargo including organelles, proteins, or intracellular pathogens are targeted for selective autophagy is limited 3 . We employed quantitative proteomics to identify a cohort of novel and known autophagosome-enriched proteins, including cargo receptors. Like known cargo receptors, NCOA4 was highly enriched in autophagosomes, and associated with ATG8 proteins that recruit cargo-receptor complexes into autophagosomes. Unbiased identification of NCOA4-associated proteins revealed ferritin heavy and light chains, components of an iron-filled cage structure that protects cells from reactive iron species 4 but is degraded via autophagy to release iron 5,6 through an unknown mechanism. We found that delivery of ferritin to lysosomes required NCOA4, and an inability of NCOA4-deficient cells to degrade ferritin leads to decreased bioavailable intracellular iron. This work identifies NCOA4 as a selective cargo receptor for autophagic turnover of ferritin (ferritinophagy) critical for iron homeostasis and provides a resource for further dissection of autophagosomal cargo-receptor connectivity.
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            The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis.

            Stress influences circulating inflammatory markers, and these effects may mediate the influence of psychosocial factors on cardiovascular risk and other conditions such as psoriasis and rheumatoid arthritis. Inflammatory responses can be investigated under controlled experimental conditions in humans, and evidence is beginning to emerge showing that circulating inflammatory factors respond to acute psychological stress under laboratory conditions. However, research published to date has varied greatly in the composition of study groups, the timing of samples, assay methods, and the type of challenge imposed. The purpose of this review is to synthesize existing data using meta-analytic techniques. Thirty studies met inclusion criteria. Results showed robust effects for increased levels of circulating IL-6 (r=0.19, p=0.001) and IL-1beta (r=0.58, p<0.001) following acute stress, and marginal effects for CRP (r=0.12, p=0.088). The effects of stress on stimulated cytokine production were less consistent. Significant variation in the inflammatory response was also related to the health status of participants and the timing of post-stress samples. A number of psychobiological mechanisms may underlie responses, including stress-induced reductions in plasma volume, upregulation of synthesis, or enlargement of the cell pool contributing to synthesis. The acute stress-induced inflammatory response may have implications for future health, and has become an important topic of psychoneuroimmunological research.
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              Critical period regulation.

              Neuronal circuits are shaped by experience during critical periods of early postnatal life. The ability to control the timing, duration, and closure of these heightened levels of brain plasticity has recently become experimentally accessible, especially in the developing visual system. This review summarizes our current understanding of known critical periods across several systems and species. It delineates a number of emerging principles: functional competition between inputs, role for electrical activity, structural consolidation, regulation by experience (not simply age), special role for inhibition in the CNS, potent influence of attention and motivation, unique timing and duration, as well as use of distinct molecular mechanisms across brain regions and the potential for reactivation in adulthood. A deeper understanding of critical periods will open new avenues to "nurture the brain"-from international efforts to link brain science and education to improving recovery from injury and devising new strategies for therapy and lifelong learning.
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                Author and article information

                Journal
                Pharmaceuticals (Basel)
                Pharmaceuticals (Basel)
                pharmaceuticals
                Pharmaceuticals
                MDPI
                1424-8247
                29 August 2019
                September 2019
                : 12
                : 3
                : 126
                Affiliations
                [1 ]Centro Interdisciplinar de Ciências Sociais (CICS.NOVA), Faculdade de Ciências Sociais e Humanas da Universidade NOVA de Lisboa (NOVA FCSH), 1069-061 Lisbon, Portugal
                [2 ]School of Business and Economics, NOVA University of Lisbon, 2775-405 Lisbon, Portugal
                [3 ]Chronic Diseases Research Center (CEDOC)/NOVA Medical School, Universidade NOVA de Lisboa, 1180-052, 1150-082 Lisbon, Portugal
                Author notes
                Article
                pharmaceuticals-12-00126
                10.3390/ph12030126
                6789770
                31470556
                96a8ead8-00c2-4833-834c-b5003e76c5b0
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 05 August 2019
                : 27 August 2019
                Categories
                Review

                iron,brain,neurophysiology,cognition,social behavior
                iron, brain, neurophysiology, cognition, social behavior

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