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Manganese brain

Supak Jenkitkasemwong, Adenike Akinyode, Elizabeth Paulus, Ralf Weiskirchen, Shintaro Hojyo, Toshiyuki Fukada, Genesys Giraldo, Jessica Schrier, Armin Garcia, Christopher Janus, Benoit Giasson, Mitchell D Knutson
Solute carrier family 39, member 14 (SLC39A14) is a transmembrane transporter that can mediate the cellular uptake of zinc, iron, and manganese (Mn). Studies of Slc39a14 knockout ( Slc39a14 -/- ) mice have documented that SLC39A14 is required for systemic growth, hepatic zinc uptake during inflammation, and iron loading of the liver in iron overload. The normal physiological roles of SLC39A14, however, remain incompletely characterized. Here, we report that Slc39a14 -/- mice spontaneously display dramatic alterations in tissue Mn concentrations, suggesting that Mn is a main physiological substrate for SLC39A14...
February 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
Roberto G Lucchini, Michael Aschner, Philip J Landrigan, Joan M Cranmer
Manganese is an essential trace element, but also at high levels a neurotoxicant. Manganese neurotoxicity has been extensively studied since its discovery in highly exposed workers. The International conference MANGANESE2016 held at the Icahn School of Medicine at Mount Sinai in New York provided relevant updates on manganese research in relation to both occupational and environmental exposures. Epidemiological, toxicological and cellular studies reported at the conference have yielded new insights on mechanisms of manganese toxicity and on opportunities for preventive intervention...
January 2018: Neurotoxicology
Carla Garza-Lombo, Yanahi Posadas, Liliana Quintanar, Maria E Gonsebatt, Rodrigo Franco
SIGNIFICANCE: Essential metals such as copper, iron, manganese and zinc play a role as cofactors in the activity of a wide range of processes involved in cellular homeostasis and survival, as well as during organ and tissue development. Throughout our lifespan, humans are also exposed to xenobiotic metals from natural and anthropogenic sources including aluminum, arsenic, cadmium, lead and mercury. It is well recognized that alterations in the homeostasis of essential metals and an increased environmental/occupational exposure to xenobiotic metals is linked to several neurological disorders including neurodegeneration and neurodevelopmental alterations...
February 5, 2018: Antioxidants & Redox Signaling
Xiao Wei, Yuan Yang, Yin-Jiu Jiang, Jian-Ming Lei, Jing-Wen Guo, Hua Xiao
The present study aimed to investigate the role of relaxin (RLX) on high glucose (HG)-induced cardiomyocyte hypertrophy and apoptosis, as well as the possible molecular mechanism. H9c2 cells were exposed to 33 mmol/l HG with or without RLX (100 nmol/ml). Cell viability, apoptosis, oxidative stress, cell hypertrophy and the levels of Notch1, hairy and enhancer of split 1 (hes1), atrial natriuretic polypeptide (ANP), brain natriuretic peptide (BNP), manganese superoxide dismutase (MnSOD), cytochrome C and caspase-3 were assessed in cardiomyocytes...
January 2018: Experimental and Therapeutic Medicine
Galit Saar, Corina M Millo, Lawrence P Szajek, Jeff Bacon, Peter Herscovitch, Alan P Koretsky
PURPOSE: Manganese ion has been extensively used as a magnetic resonance imaging (MRI) contrast agent in preclinical studies to assess tissue anatomy, function, and neuronal connectivity. Unfortunately, its use in human studies has been limited by cellular toxicity and the need to use a very low dose. The much higher sensitivity of positron emission tomography (PET) over MRI enables the use of lower concentrations of manganese, potentially expanding the methodology to humans. PROCEDURES: PET tracers manganese-51 (Mn-51, t1/2 = 46 min) and manganese-52 (Mn-52, t1/2 = 5...
February 2, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
L Marti-Sanchez, J D Ortigoza-Escobar, A Darling, M Villaronga, H Baide, M Molero-Luis, M Batllori, M I Vanegas, J Muchart, L Aquino, R Artuch, A Macaya, M A Kurian, Pérez Dueñas
BACKGROUND: The SLC39A14, SLC30A10 and SLC39A8 are considered to be key genes involved in manganese (Mn) homeostasis in humans. Mn levels in plasma and urine are useful tools for early recognition of these disorders. We aimed to explore further biomarkers of Mn deposition in the central nervous system in two siblings presenting with acute dystonia and hypermanganesemia due to mutations in SLC39A14. These biomarkers may help clinicians to establish faster and accurate diagnosis and to monitor disease progression after chelation therapy is administered...
January 30, 2018: Orphanet Journal of Rare Diseases
Luca Pasquini, Maria Camilla Rossi Espagnet, Antonio Napolitano, Daniela Longo, Alice Bertaina, Emiliano Visconti, Paolo Tomà
In the last few years, several scientific papers and reports have demonstrated magnetic resonance (MR) signal intensity (SI) changes on pre-contrast T1-weighted images following multiple gadolinium-based contrast agents (GBCA) administrations, particularly following the exposure to linear GBCAs. Pathological animal and human post-mortem studies have confirmed the relationship between this radiological finding and the presence of gadolinium accumulation in vulnerable brain regions in patients with normal renal function...
January 27, 2018: La Radiologia Medica
Giovanna Casili, Michela Campolo, Irene Paterniti, Marika Lanza, Alessia Filippone, Salvatore Cuzzocrea, Emanuela Esposito
TBI is a serious neuropathology that causes secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory and cytotoxic processes. Fumaric acid esters (FAEs) showed beneficial effects in preclinical models of neuroinflammation and toxic oxidative stress, so the aim of the present work was to evaluate the potential beneficial effects of dimethyl fumarate (DMF), the most pharmacologically effective molecules among the FAEs, in a mouse model of TBI induced by controlled cortical impact (CCI)...
January 23, 2018: Journal of Neurotrauma
Daniel J Huereca, Konstandinos A Bakoulas, Farhad Ghoddoussi, Bruce A Berkowitz, Avril Genene Holt, Patrick J Mueller
Spinally projecting neurons in the rostral ventrolateral medulla (RVLM) are believed to contribute to pathophysiological alterations in sympathetic nerve activity and the development of cardiovascular disease. The ability to identify changes in the activity of RVLM neurons in conscious animals and humans, especially longitudinally, would represent a clinically important advancement in our understanding of the contribution of the RVLM to cardiovascular disease. To this end, we describe the initial development of manganese-enhanced magnetic resonance imaging (MEMRI) for the rat RVLM...
January 12, 2018: NMR in Biomedicine
Tong-Yu Wang, Zhuo Ma, Can Wang, Chang Liu, Dong-Ying Yan, Yu Deng, Wei Liu, Zhao-Fa Xu, Bin Xu
Overexposure to Manganese (Mn) has been known to disrupt neurotransmitter release in the brain. However, the underlying mechanisms of Mn exposure on neurotransmitter vesicle release are still unclear. The current study investigated whether Mn-induced alpha-synuclein protein overexpression could disrupt the Rab3 cycle leading to synaptic vesicle fusion dysfunction. After the neurons were exposed to Mn (100 μM) for 0, 6, 12, 24 h, [Ca2+]i, alpha-synuclein and Rab3A-GTP protein expression increased gradually...
March 15, 2018: Toxicology Letters
Benedikt T Bedenk, Suellen Almeida-Corrêa, Angela Jurik, Nina Dedic, Barbara Grünecker, Andreas J Genewsky, Sebastian F Kaltwasser, Caitlin J Riebe, Jan M Deussing, Michael Czisch, Carsten T Wotjak
Manganese-enhanced magnetic resonance imaging (MEMRI) exploits the biophysical similarity of Ca2+ and Mn2+ to map the brain's activity in vivo. However, to what extent different Ca2+ channels contribute to the enhanced signal that MEMRI provides and how Mn2+ dynamics influence Mn2+ brain accumulation after systemic administration of MnCl2 are not yet fully understood. Here, we demonstrate that mice lacking the L-type Ca2+ channel 1.2 (Cav1.2) in the CNS show approximately 50% less increase in MEMRI contrast after repeated systemic MnCl2 injections, as compared to control mice...
December 19, 2017: NeuroImage
Pavel Svehla, Alexis Bédécarrats, Caroline Jahn, Romuald Nargeot, Luisa Ciobanu
BACKGROUND: Manganese-enhanced magnetic resonance imaging (MEMRI) is an increasingly popular alternative to standard functional MRI methods in animal studies. The contrast in MEMRI images is based on the accumulation of Mn2+ ions inside neurons, and, since manganese can serve as calcium analogue, this accumulation reflects calcium dynamics providing versatile information about brain neuroarchitecture and functionality. However, despite its use as a functional imaging tool, the exact relationship between the MEMRI signal and neuronal activity remains elusive...
December 14, 2017: Journal of Neuroscience Methods
Lei Wang, HuanHuan Fu, Bin Liu, XiaoYan Liu, WeiWei Chen, XiaoDan Yu
Overexposure to manganese (Mn) is associated with neurological disorders in children. Evidence indicated that N-methyl-d-aspartate (NMDA) receptor signaling pathway was critical for neurobehavioral function. However, whether NMDA receptor signaling pathway contributes to Mn-induced neurotoxicity remains unknown. In this study, newborn Sprague-Dawley rats were randomly assigned to four groups exposed to 0, 10, 20, and 30 mg/kg of Mn2+ by intraperitoneal injection (n = 10/group: five males and five females)...
December 4, 2017: Journal of Biochemical and Molecular Toxicology
Yung-Kang Peng, Cathy N P Lui, Yu-Wei Chen, Shang-Wei Chou, Pi-Tai Chou, Ken K L Yung, S C Edman Tsang
Tagging recognition group(s) on superparamagnetic iron oxide is known to aid localisation (imaging), stimulation and separation of biological entities using magnetic resonance imaging (MRI) and magnetic agitation/separation (MAS) techniques. Despite the wide applicability of iron oxide nanoparticles in T 2-weighted MRI and MAS, the quality of the images and safe manipulation of the exceptionally delicate neural cells in a live brain are currently the key challenges. Here, we demonstrate the engineered manganese oxide clusters-iron oxide core-shell nanoparticle as an MR dual-modal contrast agent for neural stem cells (NSCs) imaging and magnetic manipulation in live rodents...
December 5, 2017: Nanotechnology
Chang Liu, Dong-Ying Yan, Xuan Tan, Zhuo Ma, Can Wang, Yu Deng, Wei Liu, Tian-Yao Yang, Zhao-Fa Xu, Bin Xu
Overexposure to manganese (Mn) has been known to induce alpha-synuclein (α-Syn) oligomerization, which is degraded mainly depending on endoplasmic reticulum stress (ER stress) and autophagy pathways. However, little data reported the cross-talk between ER stress and autophagy on Mn-induced α-Syn oligomerization. To explore the relationship between ER stress and autophagy, we used 4-phenylbutyric acid (4-PBA, the ER stress inhibitor), rapamycin (Rap, autophagy activator) and 3-methyladenine (3-MA, autophagy inhibitor) in mice model of manganism...
November 29, 2017: Environmental Toxicology
Jennifer Jin, Olivia Saqui, Johane P Allard
BACKGROUND: Manganese (Mn) is included in current premixed multiple trace element (TE) additives for home parenteral nutrition (HPN). However, there is a risk of oversupplementation of Mn due to contamination from PN additives. Oversupplementation can produce Mn toxicity with neurologic symptoms and abnormalities on brain magnetic resonance imaging (MRI). In 2009, we reported that whole-blood Mn levels were above the upper limit of normal in 16 HPN patients, with 81% having MRI findings...
March 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
Jasenka Zubcevic, Jacqueline Watkins, Pablo D Perez, Luis M Colon-Perez, Maureen T Long, Marcelo Febo, Linda Hayward
Individuals with anxiety/depression often have exaggerated cardiovascular responses to stressful stimuli and a comorbidity with hypertension. Alternatively, individuals with hypertension can be more anxious. In the present study cardiovascular changes were evaluated during behavioral testing of anxious behavior on the elevated plus maze (EPM) in the spontaneously hypertensive rat (SHR), a rodent model of neurogenic hypertension, and compared to the response of the more anxious, but normotensive, Wistar-Kyoto rat (WKY)...
November 27, 2017: Brain Imaging and Behavior
Hye-Sun Lim, Bu-Yeo Kim, Yu Jin Kim, Soo-Jin Jeong
Allylguaiacol is a phytochemical occurring in various plants such as cloves, cinnamon, basil, and nutmeg. Pharmacological effects of allylguaiacol include antimicrobial, anti-inflammatory, anticancer, antioxidant, and neuroprotective activity. Although allylguaiacol is considered to have neuroprotective effects, there is no report on its regulatory mechanisms at the molecular level. In the present study, we investigated the mechanisms of allylguaiacol as an antioxidant and neuroprotective agent using hydrogen peroxide (H2O2)-treated HT22 hippocampal cells...
November 7, 2017: Behavioural Brain Research
Mikaela A Laine, Ewa Sokolowska, Mateusz Dudek, Saija-Anita Callan, Petri Hyytiä, Iiris Hovatta
Chronic psychosocial stress is a well-established risk factor for neuropsychiatric diseases. Abnormalities in brain activity have been demonstrated in patients with stress-related disorders. Global brain activation patterns during chronic stress exposure are less well understood but may have strong modifying effects on specific brain circuits and thereby influence development of stress-related pathologies. We determined neural activation induced by chronic social defeat stress, a mouse model of psychosocial stress...
November 8, 2017: Scientific Reports
Jingjing Li, Chen Wu, Pingfu Hou, Min Zhang, Kai Xu
Magnetic resonance imaging (MRI) contrast agents have become a necessary part for clinical practice to improve the sensitivity for the diagnosis of small lesions and injuries. Among them, manganese oxide nanoparticle (MnO NPs)-based MRI contrast agent attracts more and more attention because of their better performance in the detection of brain disease and positive enhancement in T1-weighted image. However, the relatively low r1 relaxivity and complex synthetic route hampered their wider applications. In this work, we proposed a one-pot approach to prepare hydrophilic MnO NPs via a polyol-like method with poly (ethylene glycol) (PEG) as both a solvent and surfactant...
October 27, 2017: Biosensors & Bioelectronics
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