Gut Microbiota as a Potential Player in Mn-Induced Neurotoxicity.

Manganese (Mn) is an essential metal, which at high exposures causes neurotoxic effects and neurodegeneration. The neurotoxic effects of Mn are mediated by neuroinflammation, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, and other mechanisms. Recent findings have demonstrated the potential impact of Mn overexposure on gut microbiota dysbiosis, which is known to contribute to neurodegeneration via secretion of neuroactive and proinflammatory metabolites. Therefore, in this review, we discuss the existing data on the impact of Mn exposure on gut microbiota biodiversity, bacterial metabolite production, and gut wall permeability regulating systemic levels. Recent data have demonstrated that Mn exposure may affect gut microbiota biodiversity by altering the abundance of Shiegella, Ruminococcus, Dorea, Fusicatenibacter, Roseburia, Parabacteroides, Bacteroidetes, Firmicutes, Ruminococcaceae, Streptococcaceae, and other bacterial phyla. A Mn-induced increase in Bacteroidetes abundance and a reduced Firmicutes/Bacteroidetes ratio may increase lipopolysaccharide levels. Moreover, in addition to increased systemic lipopolysaccharide (LPS) levels, Mn is capable of potentiating LPS neurotoxicity. Due to the high metabolic activity of intestinal microflora, Mn-induced perturbations in gut microbiota result in a significant alteration in the gut metabolome that has the potential to at least partially mediate the biological effects of Mn overexposure. At the same time, a recent study demonstrated that healthy microbiome transplantation alleviates Mn-induced neurotoxicity, which is indicative of the significant role of gut microflora in the cascade of Mn-mediated neurotoxicity. High doses of Mn may cause enterocyte toxicity and affect gut wall integrity through disruption of tight junctions. The resulting increase in gut wall permeability further promotes increased translocation of LPS and neuroactive bacterial metabolites to the systemic blood flow, ultimately gaining access to the brain and leading to neuroinflammation and neurotransmitter imbalance. Therefore, the existing data lead us to hypothesize that gut microbiota should be considered as a potential target of Mn toxicity, although more detailed studies are required to characterize the interplay between Mn exposure and the gut, as well as its role in the pathogenesis of neurodegeneration and other diseases.

Magnetic molecular conductors based on BETS molecules and divalent magnetic anions [BETS = bis(ethylenedithio)tetraselenafulvalene].

Several conducting salts based on BETS [where BETS = bis(ethylenedithio)tetraselenafulvalene] molecules and divalent magnetic anions such as the (CoCl(4))(2-), (CoBr(4))(2-), and (MnBr(4))(2-) were prepared. Electrocrystallization by using the (CoCl(4))(2-) anion gave two kinds of crystals. Block-shaped crystals were cleared to be (BETS)(2)CoCl(4), which is an insulator with the high-spin state of cobalt 3d spin. On the other hand, the X-ray crystal structure analysis of a plate-shaped crystal of the (CoCl(4))(2-) salt revealed the system to be kappa-(BETS)(4)CoCl(4)(EtOH), which is metallic down to 0.7 K. The electronic band structure calculation gave a typical two-dimensional cylindrical Fermi surface. However, there is only very weak antiferromagnetic interaction between the S = 3/2 cobalt 3d spins because of its anion-solvent-intermingled layer structure. On the other hand, the electrocrystallization by using the (MnBr(4))(2-) anion yielded the plate-shaped black crystals of the (MnBr(4))(2-) salt. Crystal structure analysis of the (MnBr(4))(2-) salt showed that the salt is theta;-(BETS)(4)MnBr(4)(EtOH)(2) with alternating donor and anion-solvent mixed layers. The stacking direction in one donor layer is perpendicular to those of the neighboring layers. The electrical and magnetic properties of the theta;-(BETS)(4)MnBr(4)(EtOH)(2) salt showed the metallic behavior down to approximately 30 K and the paramagnetism of the high-spin manganese 3d spins. Band structure calculation of this salt gave an elliptical cylindrical Fermi surface. Because the Fermi surfaces of the adjacent donor layers are rotated to each other by 90 degrees, the theta-(BETS)(4)MnBr(4)(EtOH)(2) salt becomes a two-dimensionally isotropic metal.