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Manganese brain

Branka Popović, Milica Velimirović, Tihomir Stojković, Gavrilo Brajović, Silvio R De Luka, Ivan Milovanović, Srdjan Stefanović, Dragica Nikolić, Jasna L Ristić-Djurović, Nataša D Petronijević, Alexander M Trbovich
Ageing affects various physiological and metabolic processes in a body and a progressive accumulation of oxidative damage stands out as often used explanation. One of the most powerful scavenger of reactive oxygen species (ROS) in all organs is melatonin. A majority of melatonin supplied to the body via blood originates from the pineal gland. However, we have been interested in a locally produced melatonin. We have used 2.5- and 36-months-old Wistar rats. Tissues were collected and gene expression of AA-NAT and ASMT, the two key enzymes in a synthesis of melatonin, was determined in brain, liver, kidney, heart, skin, and intestine...
June 12, 2018: Experimental Gerontology
Sean X Naughton, Caterina M Hernandez, Wayne D Beck, Indrani Poddar, Nathan Yanasak, Ping-Chang Lin, Alvin V Terry
Organophosphates (OPs) are found in hundreds of valuable agricultural, industrial, and commercial compounds; however, they have also been associated with a variety of harmful effects in humans. The acute toxicity of OPs is attributed to the inhibition of the enzyme acetylcholinesterase (AChE); however, this mechanism may not account for all of the deleterious neurologic effects of OPs, especially at doses that produce no overt signs of acute toxicity. In this study, the effects of two weeks of daily subcutaneous exposure to the OP-nerve agent diisopropylfluorophosphate (DFP) in doses ranging from 0...
June 9, 2018: Toxicology
Suellen Almeida-Corrêa, Michael Czisch, Carsten T Wotjak
Manganese-enhanced magnetic resonance imaging (MEMRI) is a powerful tool for in vivo non-invasive whole-brain mapping of neuronal activity. Mn2+ enters active neurons via voltage-gated calcium channels and increases local contrast in T1 -weighted images. Given the property of Mn2+ of axonal transport, this technique can also be used for tract tracing after local administration of the contrast agent. However, MEMRI is still not widely employed in basic research due to the lack of a complete description of the Mn2+ dynamics in the brain...
2018: Frontiers in Neural Circuits
JunJun Ling, Shengyou Yang, Yi Huang, Dongfeng Wei, Weidong Cheng
Alzheimer disease (AD) is a progressive neurodegenerative disease, the etiology of which remains largely unknown. Accumulating evidence indicates that elevated manganese (Mn) in brain exerts toxic effects on neurons and contributes to AD development. Thus, we aimed to explore the gene and pathway variations through analysis of high through-put data in this process.To screen the differentially expressed genes (DEGs) that may play critical roles in Mn-induced AD, public microarray data regarding Mn-treated neurocytes versus controls (GSE70845), and AD versus controls (GSE48350), were downloaded and the DEGs were screened out, respectively...
June 2018: Medicine (Baltimore)
Juan Sanchez-Ramos, Shijie Song, Xiaoyuan Kong, Parastou Foroutan, Gary Martinez, William Dominguez-Viqueria, Shyam Mohapatra, Subhra Mohapatra, Reka A Haraszti, Anastasia Khvorova, Neil Aronin, Vasyl Sava
The overall objective of the present research was to develop a nanocarrier system for non-invasive delivery to brain of molecules useful for gene therapy. Manganese-containing nanoparticles (mNPs) carrying anti -eGFP siRNA were tested in cell cultures of eGFP-expressing cell line of mouse fibroblasts (NIH3T3). The optimal mNPs were then tested in vivo in mice. Following intranasal instillation, mNPs were visualized by 7T MRI throughout brain at 24 and 48 hrs. mNPs were effective in significantly reducing GFP mRNA expression in Tg GFP+ mice in olfactory bulb, striatum, hippocampus and cortex...
February 2018: Journal of Drug Delivery Science and Technology
Abhijit Das, Md Shahid Sarwar, Md Shohel Hossain, Palash Karmakar, Mohammad Safiqul Islam, Mohammad Enayet Hussain, Sujan Banik
BACKGROUND: Epilepsy is one of the chronic and heterogeneous epidemic neurological disorders leading to substantial mortality. The aim of the present study was to investigate the serum levels of malondialdehyde (MDA), vitamin C, and trace elements namely zinc (Zn), copper (Cu), and manganese (Mn) in epileptic patients of Bangladesh and to establish if there are any pathophysiological correlations. METHODS: This was a case-control study with 40 generalized epileptic patients and 40 healthy subjects as controls...
May 1, 2018: Clinical EEG and Neuroscience: Official Journal of the EEG and Clinical Neuroscience Society (ENCS)
James Johnson, Edward Pajarillo, Pratap Karki, Judong Kim, Deok-Soo Son, Michael Aschner, Eunsook Lee
Exposure to elevated levels of manganese (Mn) causes manganism, a neurological disorder with similar characteristics to those of Parkinson's disease (PD). Valproic acid (VPA), an antiepileptic, is known to inhibit histone deacetylases and exert neuroprotective effects in many experimental models of neurological disorders. In the present study, we investigated if VPA attenuated Mn-induced dopaminergic neurotoxicity and the possible mechanisms involved in VPA's neuroprotection, focusing on modulation of astrocytic glutamate transporters (glutamate aspartate transporter, GLAST and glutamate transporter 1, GLT-1) and histone acetylation in H4 astrocyte culture and mouse models...
May 17, 2018: Neurotoxicology
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No abstract text is available yet for this article.
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
Rui Xue Zhang, Jason Li, Tian Zhang, Mohammad A Amini, Chunsheng He, Brian Lu, Taksim Ahmed, HoYin Lip, Andrew M Rauth, Xiao Yu Wu
Nanotechnology has been applied extensively in drug delivery to improve the therapeutic outcomes of various diseases. Tremendous efforts have been focused on the development of novel nanoparticles and delineation of the physicochemical properties of nanoparticles in relation to their biological fate and functions. However, in the design and evaluation of these nanotechnology-based drug delivery systems, the pharmacology of delivered drugs and the (patho-)physiology of the host have received less attention. In this review, we discuss important pharmacological mechanisms, physiological characteristics, and pathological factors that have been integrated into the design of nanotechnology-enabled drug delivery systems and therapies...
May 2018: Acta Pharmacologica Sinica
Qin Yu, Yuan-Zhong Zhou
Alzheimer disease (AD) is a neurodegenerative disease. Manganese (Mn) is an essential trace element in the human body. It can enter the brain through the blood-brain barrier and blood-cerebrospinal fluid barrier. Excessive accumulation of Mn in the brain may disturb the homeostasis of the central nervous system (CNS) microenvironment and cause severe neuronal damage. The most recent data suggest that excessive Mn is associated with impaired learning and memory in animal models, and may lead to irreversible and progressive mild cognitive impairment and AD...
April 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Lance H Rodan, Marissa Hauptman, Alissa M D'Gama, Anita E Qualls, Siqi Cao, Karin Tuschl, Fatma Al-Jasmi, Jozef Hertecant, Susan J Hayflick, Marianne Wessling-Resnick, Edward T Yang, Gerard T Berry, Andrea Gropman, Alan D Woolf, Pankaj B Agrawal
Congenital disorders of manganese metabolism are rare occurrences in children, and medical management of these disorders is complex and challenging. Homozygous exonic mutations in the manganese transporter SLC39A14 have recently been associated with a pediatric-onset neurodegenerative disorder characterized by brain manganese accumulation and clinical signs of manganese neurotoxicity, including parkinsonism-dystonia. We performed whole exome sequencing on DNA samples from two unrelated female children from the United Arab Emirates with progressive movement disorder and brain mineralization, identified a novel homozygous intronic mutation in SLC39A14 in both children, and demonstrated that the mutation leads to aberrant splicing...
June 2018: Molecular Genetics and Metabolism
Cailing Lu, Zhijuan Meng, Yiyuan He, Deqiang Xiao, Haiqing Cai, Yilu Xu, Xianghong Liu, Xinhang Wang, Laiming Mo, Ziwei Liang, Xuejing Wei, Qingqing Ao, Boying Liang, Xiyi Li, Shen Tang, Songchao Guo
Glutamate excitotoxicity, characterized as excessive glutamate stress, is considered to be involved in cerebral ischaemia, brain trauma, and neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Glutamate homeostasis disruption was highlighted in Mn neurotoxicity caused by high levels of Mn. Astrocytes, accounting for approximately 50% of the neuronal cells in the central nervous system and maintain glutamate homeostasis, are sensitive to neurotoxicity induced by Mn exposure. Astrocytes are tightly coupled with gap junctions (GJ), which are comprised of connexins, mainly connexin43 (Cx43)...
April 17, 2018: Brain Research Bulletin
Rania I Nadeem, Hebatalla I Ahmed, Bahia M El-Sayeh
Manganese (Mn) is required for many essential biological processes as well as in the development and functioning of the brain. Extensive accumulation of Mn in the brain may cause central nervous system dysfunction known as manganism, a motor disorder associated with cognitive and neuropsychiatric deficits similar to parkinsonism. Vinpocetine, a synthetic derivative of the alkaloid vincamine, is used to improve the cognitive function in cerebrovascular diseases. It possesses antioxidant and antiinflammatory properties...
July 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Cyrus S H Ho, Roger C M Ho, Amy M L Quek
Heavy metal poisoning is a rare but important cause of encephalopathy. Manganese (Mn) toxicity is especially rare in the modern world, and clinicians’ lack of recognition of its neuropsychiatric manifestations can lead to misdiagnosis and mismanagement. We describe the case of a man who presented with recurrent episodes of confusion, psychosis, dystonic limb movement and cognitive impairment and was initially diagnosed with anti-voltage-gated potassium channel (VGKC) complex limbic encephalitis in view of previous positive autoantibodies...
April 18, 2018: International Journal of Environmental Research and Public Health
Aaron K Apawu, Stephanie M Curley, Angela R Dixon, Mirabela Hali, Moaz Sinan, Rod D Braun, James Castracane, Anthony T Cacace, Magnus Bergkvist, Avril Genene Holt
Fundamental challenges of targeting specific brain regions for treatment using pharmacotherapeutic nanoparticle (NP) carriers include circumventing the blood-brain-barrier (BBB) and tracking delivery. Angiopep-2 (AP2) has been shown to facilitate the transport of large macromolecules and synthetic nanoparticles across the BBB. Thus, conjugation of AP2 to an MS2 bacteriophage based NP should also permit transport across the BBB. We have fabricated and tested a novel MS2 capsid-based NP conjugated to the ligand AP2...
April 14, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Kelly E Bosse, Farhad Ghoddoussi, Ajay T Eapen, Jennifer L Charlton, Laura L Susick, Kirt Desai, Bruce A Berkowitz, Shane A Perrine, Alana C Conti
Evidence suggests a predictive link between elevated basal activity within reward-related networks (e.g., cortico-basal ganglia-thalamic networks) and vulnerability for alcoholism. Both calcium channel function and cyclic adenosine monophosphate (cAMP)/protein kinase A-mediated signaling are critical modulators of reward neurocircuitry and reward-related behaviors. Calcium/calmodulin-stimulated adenylyl cyclases (AC) 1 and 8 are sensitive to activity-dependent increases in intracellular calcium and catalyze cAMP production...
March 28, 2018: Brain Imaging and Behavior
Sherleen Xue-Fu Adamson, Xubo Shen, Wendy Jiang, Vivien Lai, Xiaoting Wang, Jonathan H Shannahan, Jason R Cannon, Jinhui Chen, Wei Zheng
Adult neurogenesis takes place in the brain subventricular zone (SVZ) in the frontal cortex and subgranular zone (SGZ) in the hippocampal dentate gyrus (HDG), and functions to supply newborn neurons for normal brain functionality. Subchronic Mn exposure is known to disrupt adult neurogenesis in the SVZ. This study was designed to determine whether Mn exposure disturbed neurogenesis within the adult HDG. Adult rats (10 weeks old) received a single dose of BrdU at the end of 4-wk Mn exposure to label the proliferating cells...
March 21, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Dennis Guilherme Costa-Silva, Andressa Rubim Lopes, Illana Kemmerich Martins, Luana Paganotto Leandro, Mauro Eugênio Medina Nunes, Nelson Rodrigues de Carvalho, Nathane Rosa Rodrigues, Giulianna Echeveria Macedo, Ana Paula Saidelles, Cassiana Aguiar, Morgana Doneda, Erico Marlon Moraes Flores, Thais Posser, Jeferson Luis Franco
Manganese (Mn)-containing dithiocarbamates such as Mancozeb (MZ) have been shown to induce oxidative stress-related toxicity in rodents and humans. However, little is known about the neurotoxic effects induced by MZ in fish. In this study, carp (Cyprinus carpio) were exposed to non-lethal waterborne concentrations of MZ, and oxidative stress parameters as well as metal accumulation in fish brains were evaluated. The experimental groups were as follows: control, MZ 5 mg/L, and MZ 10 mg/L. Fish were exposed for 7 days, and then brain was removed and prepared for subsequent analysis of antioxidant enzymes, reactive oxygen species (ROS), and expression of Nrf2 and phosphoNrf2...
March 22, 2018: Environmental Science and Pollution Research International
Mattias Günther, Faiez Al Nimer, Fredrik Piehl, Mårten Risling, Tiit Mathiesen
Traumatic brain injury (TBI) leads to a deleterious and multifactorial secondary inflammatory response in the brain. Oxidative stress from the inflammation likely contributes to the brain damage although it is unclear to which extent. A largely unexplored approach is to consider phenotypic regulation of oxidative stress levels. Genetic polymorphism influences inflammation in the central nervous system and it is possible that the antioxidative response differs between phenotypes and affects the severity of the secondary injury...
March 2018: ENeuro
Yehuda Ben-Shahar
Manganese (Mn) is an essential trace element that acts as a metal co-factor in diverse biochemical and cellular functions. However, chronic environmental exposure to high levels of Mn is a well-established risk factor for the etiology of severe, atypical parkinsonian syndrome (manganism) via its accumulation in the basal ganglia, pallidum, and striatum brain regions, which is often associated with abnormal dopamine, GABA, and glutamate neural signaling. Recent studies have indicated that chronic Mn exposure at levels that are below the risk for manganism can still cause behavioral, cognitive, and motor dysfunctions via poorly understood mechanisms at the molecular and cellular levels...
2018: Frontiers in Genetics
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