Molecular neurochemistry of the lanthanides

Abstract

Lanthanides, once termed rare‐earth elements, are not as sparce in the environment as their traditional name suggests. Mean litospheric concentrations are in fact comparable to the physiologically fundamental elements such as iodine, cobalt, and selenium. Recent advances in medical technology have resulted in accumulation of lanthanides presenting potential exposure to both our central and peripheral nervous systems. Extensive and detailed studies on these peculiar active metals in the context of their influence on neural functions are therefore urgently required. Almost all neurochemical effects of trivalent lanthanide ions appear to result from the similarity of their radii to the key signaling ion calcium. Lanthanides, especially La3+ and Gd3+ block different types of calcium, potassium, and sodium channels in human and animal neurons, regulate neurotransmitter turnover and release, as well as synaptic activity. Lanthanides also act as modulators of several ionotropic receptors, e.g., GABA, NMDA, and kainate and can also affect numerous signaling mechanisms including NF‐κB and apoptotic‐related endoplasmic reticulum IRE1‐XBP1, PERK, and ATF6 pathways. Several lanthanide ions may cause oxidative neuronal injuries and functional impairment by promoting reactive oxygen species production. However, cerium and yttrium oxides have some unique and promising neuroprotective properties, being able to decrease free radical cell injury and even alleviate motor impairment and cognitive function in animal models of multiple sclerosis and mild traumatic brain damage, respectively. In conclusion, lanthanides affect various neurophysiological processes, altering a large spectrum of brain functions. Thus, a deeper understanding of their potential mechanistic roles during disease and as therapeutic agents requires urgent elucidation.

Occurrence of Volcanogenic Inorganic Mercury in Wild Mice Spinal Cord: Potential Health Implications

“…In previous studies carried out in the same location in the Azores archipelago, mice living in volcanic environments showed mercury deposits in different locations of the brain [26], as well as reactive astrogliosis in the hippocampal gyrus and astrocytic dysfunction [27]. These findings could indicate that a neuroinflammatory response is occurring and, if sustained over time, it would provoke a scenario of chronic oxidative stress, which could trigger several degenerative diseases [62]. Similarly, the results presented here reflect that this same stress situation could occur in the spinal cord of animals exposed to gaseous mercury, triggering neurodegenerative pathologies, especially those related to the motor system.…”

Trend of the research on rare earth elements in environmental science

“…Future directions in the REE research can be suggested based on our literature search. One obvious research area is the investigation of biological effects of REEs using biochemical, cell biological, and toxicological techniques (Pałasz and Czekaj 2000;Jin et al 2017;Joonas et al 2017;Turra 2018;Romero-Freire et al 2019;Dubé et al 2019;Pałasz et al 2019). Another equally important field is the remediation of REEs in the environment (Su 2017;Yuan et al 2018;Wang 2018;Cheng et al 2018;Wei et al 2019;Jalali et al 2019).…”

“…Some of the toxic effects of REEs were found to be mediated by gene expression changes (Dubé et al 2019) or by directly binding to target proteins (Pałasz and Czekaj 2000). Numerous medical technologies have revealed that various neurophysiological processes including learning and memory were also affected by lanthanides (Pałasz et al 2019;Jin et al 2017). A recent review paper extensively summarized the ecological risks of REEs on plants, animals, and humans' health (Adeel et al 2019).…”

Lanthanide conjugates as versatile instruments for therapy and diagnostics

“…[12][13][14][15][16] To avoid the cytotoxicity of free metal ions, which is mainly caused by binding to endogenous metalloproteins and subsequent structure disruption, the metals are tightly complexed with multidentate ligands. [17][18][19][20] The most prominent chelators are the macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7,10tetraacetate (DOTA) and its analogs ( Fig. 1).…”