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Anna Rickli, Karolina Kolaczynska, Marius C Hoener, Matthias E Liechti
4,4'-Dimethylaminorex (4,4'-DMAR) is a novel psychoactive substance (NPS) that appeared on the illicit drug market in addition to the psychostimulant 4-methylaminorex (4-MAR). Both substances are methylated derivatives of aminorex, an amphetamine-like anorectic used in the 1960ies and withdrawn from the marked due to severe cardiovascular toxicity. The aim of the present study was to characterize the in vitro pharmacological profiles of 4-MAR, 4,4'-DMAR, and 3,4-dimethylaminorex (3,4-DMAR, direx). We assessed norepinephrine (NE), dopamine (DA), and serotonin (5-HT) transporter inhibition potencies and monoamine release in transporter-transfected human embryonic kidney (HEK) 293 cells...
February 15, 2019: Neurotoxicology
Natalia Lobanovskaya, Alexander Zharkovsky
BACKGROUND: Neural cell adhesion molecule (NCAM) belongs to the immunoglobulin superfamily of adhesion molecules. Polysialic acid (PSA) is attached to NCAM post-translationally. PSA residues are considered to reduce the adhesive properties of NCAM and play an important role in the regulation of cell interactions. PSA-NCAM is largely expressed in the mature retina by glial cells adjacent to retinal ganglion cells (RGCs) but its functions remain unclear. The objective of this study was to explore the role of PSA-NCAM with respect to RGC survival following kainic acid (KA)-induced excitotoxicity...
February 14, 2019: Neurotoxicology
Steven R Boomhower, M Christopher Newland
Gestational exposure to methylmercury (MeHg), an environmental neurotoxicant, and adolescent administration of d-amphetamine (d-AMP) disrupt dopamine neurotransmission and alter voluntary behavior in adult rodents. We determined the impact of adolescent exposure to MeHg and d-AMP on monoamine neurotransmission in mice by assessing sensitivity to acute d-AMP, desipramine, and clomipramine, drugs that target dopamine, norepinephrine, and serotonin reuptake, respectively. Male C57Bl/6n mice were given 0 (control) or 3 ppm MeHg via drinking water from postnatal day 21 to 60 (murine adolescence)...
February 12, 2019: Neurotoxicology
Jinlei Xi, Juan Liu, Shijing He, Wanyao Shen, Cizhao Wei, Ke Li, Yufeng Zhang, Jiang Yue, Zheqiong Yang
In view of the wide application of fluoroquinolones (FQs), a group of broad-spectrum synthetic antibacterial agents, and their large ingress into the environment, the toxic effects on non-target organisms caused by FQs have received great attention. In this study, we used zebrafish embryo as a model, measured the general toxic effects of norfloxacin, a commonly used FQs, and investigated the effects of norfloxacin on the neurodevelopment of zebrafish embryos. Our data showed that norfloxacin significantly inhibited the hatching rate of zebrafish embryos, and increased the mortality and malformation rate of the embryos...
February 12, 2019: Neurotoxicology
Letizia Mattii, Carla Pardini, Chiara Ippolito, Francesco Bianchi, Antonietta Raffaella, Maria Sabbatini, Francesca Vaglini
Mesencephalic cell cultures are a good model to study the vulnerability of dopaminergic neurons and reproduce, in vitro, experimental models of Parkinson's disease. Rotenone associated as an environmental neurotoxin related to PD, is able to provoke dopaminergic neuron degeneration by inhibiting complex I of the mitochondrial respiratory chain and by inducing accumulation of α-synuclein. Recently, rotenone has been described to activate RhoA, a GTPase protein. In the present study we evaluated a possible neuroprotective effect of Rho-inhibitor molecules on rotenone-damaged dopaminergic (DA) neurons obtained from mouse primary mesencephalic cell culture...
February 12, 2019: Neurotoxicology
Saghar Keshavarzi, Sareh Kermanshahi, Leila Karami, Majid Motaghinejad, Manijeh Motevalian, Samira Sadr
BACKGROUND: Methamphetamine is a neuro-stimulant with neurodegenerative effects, and ambiguous mechanism of action. Metformin is an antidiabetic agent with neuroprotective properties but not fully understood mechanisms. The present study investigated the molecular basis of metformin neuroprotection against methamphetamine-induced neurodegeneration. BRIEF METHOD: Sixty adult male rats were randomly divided into six groups: group 1 (received normal saline), group 2 (received 10 mg/kg of methamphetamine) and groups 3, 4, 5 and 6 [received methamphetamine (10 mg/kg) plus metformin (50, 75, 100 and 150 mg/kg) respectively]...
February 8, 2019: Neurotoxicology
Adnan Khan, Bushra Shal, Muhammad Naveed, Fawad Ali Shah, Ayesha Atiq, Naseem Ullah Khan, Yeong Shik Kim, Salman Khan
Acute or chronic liver injury is associated with hyperammonemia which induced neuroinflammation and oxidative stress in the brain. Neuroinflammation, oxidative stress, reduced neurogenesis, and apoptosis are critical factors for the development of anxiety and depression. The present study was aimed to evaluate the anxiolytic and antidepressant properties of matrine against acute liver injury in the rodent model. Acute liver injury in mice was induced by administration of the acute hepatotoxic dose of carbon tetrachloride (CCl4) (1 ml/kg, i...
February 7, 2019: Neurotoxicology
Takahisa Shimada, Kenji Takahashi, Makoto Tominaga, Toshio Ohta
Persulfate salts are broadly used as industrial chemicals and exposure to them causes occupational asthma, occupational rhinitis and contact dermatitis. However, the mechanisms underlying these toxic actions are not fully elucidated. Transient receptor potential (TRP) vanilloid 1 (V1), ankyrin 1 (A1) and melastatin 8 (M8) are non-selective cation channels preferentially expressing sensory neurons. These channels are known to be involved in respiratory and skin diseases. In the present study, we investigated the effects of sodium persulfate on these TRP channels...
February 6, 2019: Neurotoxicology
Mona K Galal, Ebtihal M M Elleithy, Mohamed I Abdrabou, Noha A E Yasin, Youssef M Shaheen
Lead (Pb) is a ubiquitous environmental and industrial pollutant with worldwide health problems. The present study was designed to investigate the neurotoxic effects of Pb in albino rats and to evaluate the ameliorative role of garlic as well as Spirulina maxima against such toxic effects. Forty adult male rats were used in this investigation (10 rats/group). Group I: served as control, Group II: rats received lead acetate (100 mg/kg), Group III: rats received both lead acetate (100 mg/kg) and garlic (600 mg/kg) and Group IV: rats received both lead acetate (100 mg/kg) and spirulina (500 mg/kg) daily by oral gavage for one month...
January 28, 2019: Neurotoxicology
Haruna Tamano, Hiroki Suzuki, Shuhei Kobuchi, Paul A Adlard, Ashley I Bush, Atsushi Takeda
The accumulation of amyloid-β1-42 (Aβ1-42 ), a constituively-generated peptide, in the brain is considered an upstream event in pathogenesis of Alzheimer's disease. Aβ1-42 -induced pathophysiology has been extensively studied in experimental mice and rats. However, neurotoxicity of murine Aβ1-42 is much less understood than human Aβ1-42 . Here we report difference in ability for extracellular Zn2+ influx into dentate granule cells of rats between human and rat Aβ1-42 and its significance. Human Aβ1-42 rapidly increased intracellular Zn2+ , which was determined with intracellular ZnAF-2, in dentate granule cells, 5 min after injection of Aβ1-42 (25 μM, 1 μl) into the dentate gyrus, while rat Aβ1-42 did not increase intracellular Zn2+ ...
January 18, 2019: Neurotoxicology
Michelle Vivienne Marlou Ruel, Arend Frederik Bos, Shalini Devi Soechitram, Lisethe Meijer, Pieter Jan Jacob Sauer, Sietske Annette Berghuis
BACKGROUND: Organohalogen compounds (OHCs), i.e. polychlorinated biphenyls (PCBs, are wide-spread environmental pollutants known to be neurotoxic for the developing brain. The hydroxylated metabolites of PCBs, OH-PCBs, might be even more toxic due to their structure and interference with thyroid hormone metabolism. We found that prenatal exposure to OH-PCBs was associated with thyroid hormone metabolism at toddler age. Little, however, is known about the neurotoxicity of OH-PCBs in humans...
January 18, 2019: Neurotoxicology
Haoxing Cai, Xijin Xu, Yu Zhang, Xiaowei Cong, Xueling Lu, Xia Huo
Exposure to lead is associated with adverse effects on neurodevelopment. However, studies of the effects of lead on sensory integration are few. The purpose of this research is to investigate the effect of lead exposure on child sensory integration by correlating the blood lead levels of children with sensory processing measures. A total of 574 children, from 3- to 6-years of age, 358 from an electronic waste (e-waste) recycling town named Guiyu, and 216 from Haojiang, a nearby town with no e-waste recycling activity, were recruited in this study...
January 18, 2019: Neurotoxicology
Cássio Morais Loss, Natã Sehn da Rosa, Régis Gemerasca Mestriner, Léder Leal Xavier, Diogo Losch Oliveira
Status epilepticus (SE) during developmental periods can cause short- and long-term consequences to the brain. Brain damage induced by SE is associated to NMDA receptors (NMDAR)-mediated excitotoxicity. This study aimed to investigate whether blockade of GluN2B-containing NMDAR is neuroprotective against SE-induced neurodegeneration and neuroinflammation in young rats. Forty-eight Wistar rats (16 days of life) were injected with pilocarpine (60 mg/kg; i.p.) 12-18 h after LiCl (3 mEq/kg; i.p.). Fifteen minutes after pilocarpine administration, animals received i...
January 11, 2019: Neurotoxicology
Sang-Hwan Do, Sue-Young Lee, Hyo-Seok Na
BACKGROUND: Serine synthetic pathway plays an essential role in the development and function of the nervous system. This study investigated whether the serine synthetic pathway was affected by repeated volatile anesthetic exposure using C. elegans and its relationship with anesthesia-induced neurotoxicity. METHODS: Synchronized worms were divided into two groups: the control and isoflurane groups. Worms in the isoflurane group were exposed to isoflurane for 1 h at each larval stage...
January 9, 2019: Neurotoxicology
Sunil Bhurtel, Nikita Katila, Sunil Srivastav, Sabita Neupane, Dong-Young Choi
Animal models for Parkinson's disease (PD) are very useful in understanding the pathogenesis of PD and screening for new therapeutic approaches. 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) and rotenone are common neurotoxins used for the development of experimental PD models, and both inhibit complex I of mitochondria; this is thought to be an instrumental mechanism for dopaminergic neurodegeneration in PD. In this study, we treated mice with MPTP (30 mg/kg/day) or rotenone (2.5 mg/kg/day) for 1 week and compared the neurotoxic effects of these toxins...
December 31, 2018: Neurotoxicology
Jennifer L Walters, Xuan Zhang, John C Talpos, Charles M Fogle, Mi Li, John J Chelonis, Merle G Paule
Postoperative Cognitive Dysfunction (POCD) is a complication that has been observed in a subset of adult and elderly individuals after general anesthesia and surgery. Although the pathogenesis of POCD is largely unknown, a growing body of preclinical research suggests that POCD may be caused by general anesthesia. A significant amount of research has examined the effects of general anesthesia on neurocognitive function in rodents, yet no studies have assessed the adverse effects of general anesthesia on brain function in adult nonhuman primates...
December 31, 2018: Neurotoxicology
Robert J Cooper, Maya N Menking-Colby, Kenneth A Humphrey, Jack H Victory, Daniel W Kipps, Nadja Spitzer
Silver nanoparticles (AgNPs) are increasingly incorporated in consumer products to confer antibacterial properties. AgNPs are shed during everyday use of these products,resulting in ingestion or inhalation and bioaccumulation in tissues including the brain. While these low levels of AgNPs do not induce DNA fragmentation typical of apoptosis or necrosis, they do interfere with cytoskeletal structure and dynamics in cultured differentiating adult neural stem cells (NSCs). Moreover, these cells form f-actin inclusions in response to 1 μg/ml AgNPs...
December 31, 2018: Neurotoxicology
Sergey A Menzikov, Sergey G Morozov
Phenol-induced neurotoxicity manifests as twitching/tremor and convulsions, but its molecular mechanisms underlying the behavioral responses remain unclear. We assessed the role of the brain Cl-/HCO3 --ATPase in behavioral responses in rats following an in vivo intraperitoneal injection of phenol (20-160 mg/kg). Low concentrations of phenol (20-80 mg/kg) increased the ATPase activity as well as the head twitching responses in rat, whereas higher phenol concentrations (>60 mg/kg) increased the tremor but reduced the ATPase activity...
December 24, 2018: Neurotoxicology
Jayantee Kalita, Usha K Misra, Vijay Kumar, Vasudev Parashar
BACKGROUND: There is paucity of studies on predictors of seizures in Wilson disease with neurological manifestation (WDNM), and none has evaluated the role of copper (Cu) induced oxidative stress, proinflammatory and excitotoxicity in the genesis of seizure. OBJECTIVES: To report frequency, refractoriness, and outcome of seizure in WDNM. We also evaluate role of Cu induced oxidative stress, excitotoxicity and cytokines in predicting seizures. METHODS: The diagnosis of WDNM was based on clinical, MRI, KF ring and 24 hour urinary Cu...
December 21, 2018: Neurotoxicology
Chiung-Hui Liu, Chyn-Tair Lan, Li-You Chen, Wen-Chieh Liao, Miau-Hwa Ko, To-Jung Tseng
Peripheral neuropathy, a chronic complication of diabetes mellitus (DM), is often accompanied by the onset of severe pain symptoms that affect quality of life. However, the underlying mechanisms remain elusive. In the present study, we used Sprague-Dawley rats to establish a rodent model of the human type 1 DM by a single intraperitoneal (i.p.) injection with streptozotocin (STZ) (60 mg/kg). Hypersensitivity, including hyperalgesia and allodynia, developed in the STZ-induced diabetic rats. Cutaneous innervation exhibited STZ-induced reductions of protein gene product 9...
December 21, 2018: Neurotoxicology
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