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Bingyu Ren, Yujuan Wang, Heng Wang, Yingying Wu, Jiayi Li, Jing Tian
Severity or duration of endoplasmic reticulum (ER) stress leads to two different cellular events: cell survival and apoptosis. Drug-induced ER stress or neurotoxicity has been observed as one of the main side effects. However, how ER stress affects cellular signaling cascades leading to neuronal damage is still not well understood. In this study, the toxicological mechanisms of two typical ER stress inducers, tunicamycin (Tm) and dithiothreitol (DTT), were investigated by cell viability, unfolded protein response, apoptosis and proteomic responses in mouse neuro-2a cells...
July 9, 2018: Neurotoxicology
Bryan Maloney, Baindu L Bayon, Nasser H Zawia, Debomoy K Lahiri
BACKGROUND: The lead (Pb) exposure crisis in Flint, Michigan has passed from well-publicized to a footnote, while its biological and social impact will linger for a lifetime. Interest in the "water crisis" has dropped to pre-event levels, which is neither appropriate nor safe. Flint's exposure was severe, but it was not unique. Problematic Pb levels have also been found in schools and daycares in 42 states in the USA. The enormity of Pb exposure via municipal water systems requires multiple responses...
July 5, 2018: Neurotoxicology
S Maya, Prakash T, Divakar Goli
Quinolinic acid (QUIN) is a well-known neuroactive metabolite of tryptophan degradation pathway or kynurenine pathway. The QUIN is involved in the development of several toxic cascades which leads to the neuronal degeneration processes. The QUIN-induced toxicity is also responsible for the impairment of the motor function and motor learning ability. This study seeks to investigate the several mechanisms which are involved in the intrastriatal administration of QUIN-induced neurodegeneration and the neuroprotective effects of wedelolactone (WL) and gallic acid (GA) over QUIN-induced toxicity...
July 4, 2018: Neurotoxicology
Masato Katsuyama, Masakazu Ibi, Kazumi Iwata, Misaki Matsumoto, Chihiro Yabe-Nishimura
Clioquinol was used in the mid-1900s as an amebicide to treat indigestion and diarrhea. However, it was withdrawn from the market in Japan because it was linked to subacute myelo-optic neuropathy (SMON). The pathogenesis of SMON has not yet been elucidated in detail. As reported previously, we performed a global analysis on human neuroblastoma cells using DNA chips. The global analysis and quantitative PCR demonstrated that the mRNA level of interleukin-8 (IL-8) was significantly increased when SH-SY5Y neuroblastoma cells were treated with clioquinol...
June 29, 2018: Neurotoxicology
Mina Khalilzadeh, Ghodratollah Panahi, Amir Rashidian, Mohammad Reza Hadian, Alireza Abdollahi, Khashayar Afshari, Saeed Shakiba, Abbas Norouzi-Javidan, Nastaran Rahimi, Majid Momeny, Ahmad Reza Dehpour
Clinical use of vincristine (VCR), an effective chemotherapeutic agent, has been limited due to its peripheral neuropathy toxicity. Sumatriptan, which is an anti-migraine agent is a specific agonist for 5-hydroxytryptamine 1B, 1D (5HT1B, 1D) receptors. Several studies have shown that sumatriptan exerts anti-inflammatory and immunomodulatory properties. This study aimed to investigate the effects of sumatriptan on VCR-induced peripheral neuropathy in a rat model. Male Wistar rats were intraperitoneally injected with VCR and normal saline four times per week for 2 weeks...
June 26, 2018: Neurotoxicology
Jirapa Chetsawang, Sutisa Nudmamud-Thanoi, Ruchee Phonchai, Zuroida Abubakar, Piyarat Govitrapong, Banthit Chetsawang
Methamphetamine (METH) is an addictive stimulant drug that has many negative consequences, including toxic effects to the brain. Recently, the induction of inflammatory processes has been identified as a potential contributing factor to induce neuronal cell degeneration. It has been demonstrated that the expression of inflammatory agents, such as cyclooxygenase 2 (COX-2), depends on the activation of calcineurin (CaN) and nuclear factor of activated T-cells (NFAT). Moreover, the excessive elevation in cytosolic Ca2+ levels activates the cell death process, including calpain activation in neurons, which was diminished by the overexpression of the calpain inhibitor protein, calpastatin...
June 23, 2018: Neurotoxicology
Romina Deza-Ponzio, Macarena Lorena Herrera, María José Bellini, Miriam Beatriz Virgolini, Claudia Beatriz Hereñú
Growing body of evidence suggests that mitochondrial dysfunctions and resultant oxidative stress are likely responsible for many neurodegenerative diseases, including Alzheimer´s disease (AD) and Parkinson´s disease (PD). Aldehyde dehydrogenase (ALDH) superfamily plays a crucial role in several biological processes including development and detoxification pathways in the organism. In particular, ALDH2 is crucial in the oxidative metabolism of toxic aldehydes in the brain, such as catecholaminergic metabolites (DOPAL and DOPEGAL) and the principal product of lipid peroxidation process 4-HNE...
June 21, 2018: Neurotoxicology
Chiung-Mei Chen, Wan-Ling Chen, Chen-Ting Hung, Te-Hsien Lin, Chih-Ying Chao, Chih-Hsin Lin, Yih-Ru Wu, Kuo-Hsuan Chang, Ching-Fa Yao, Guey-Jen Lee-Chen, Ming-Tsan Su, Hsiu Mei Hsieh-Li
Spinocerebellar ataxia type 17 (SCA17) is caused by the expansion of translated CAG repeat in the TATA box binding protein (TBP) gene encoding a long polyglutamine (polyQ) tract in the TBP protein, which leads to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On cells with inducible SCA17 TBP/Q79 -GFP expression to test five in-house NC009 indole compounds for neuroprotection...
June 21, 2018: Neurotoxicology
Monique Chalansonnet, Maria Carreres-Pons, Thomas Venet, Aurélie Thomas, Lise Merlen, Carole Seidel, Frédéric Cosnier, Hervé Nunge, Benoît Pouyatos, Jordi Llorens, Pierre Campo
Chronic occupational exposure to carbon disulfide (CS2) has debilitating motor and sensory effects in humans, which can increase the risk of falls. Although no mention of vestibulotoxic effects is contained in the literature, epidemiological and experimental data suggest that CS2 could cause low-frequency hearing loss when associated with noise exposure. Low-frequency noise might also perturb the peripheral balance receptor through an as-yet unclear mechanism. Here, we studied how exposure to a low-frequency noise combined with 250-ppm CS2 affected balance in rats...
June 18, 2018: Neurotoxicology
Keith Morris-Schaffer, Marissa Sobolewski, Joshua L Allen, Elena Marvin, Min Yee, Manish Arora, Michael A O'Reilly, Deborah A Cory-Slechta
Hyperoxia during treatment for prematurity may enhance susceptibility to other risk factors for adverse brain development, such as air pollution exposure, as both of these risk factors have been linked to a variety of adverse neurodevelopmental outcomes. This study investigated the combined effects of neonatal hyperoxia followed by inhalation of concentrated ambient ultrafine particles (CAPS, <100 nm in aerodynamic diameter) on learning. C57BL/6 J mice were birthed into 60% oxygen until postnatal day (PND) 4 and subsequently exposed to filtered air or to CAPS using the Harvard University Concentrated Ambient Particle System (HUCAPS) from PND 4-7 and 10-13...
June 18, 2018: Neurotoxicology
Masatake Fujimura, Fusako Usuki
Methylmercury (MeHg) induces site-specific cerebrocortical neuronal cell death. In our previous study using an in vivo mouse model, we reported that MeHg-induced cerebrocortical neuronal cell death may be due to neural hyperactivity triggered by activation of kinase pathways. However, the detailed molecular mechanism remained to be completely understood. In this study, we analyzed detailed signaling pathways for MeHg-induced neuronal cell death using all-trans-retinoic acid (RA) differentiated SH-SY5Y cells, which show neuron-like morphological changes and express neuron/synapse markers for cerebrocortical neurons...
June 15, 2018: Neurotoxicology
Anke M Tukker, Fiona M J Wijnolts, Aart de Groot, Remco H S Westerink
Neurotoxicity testing still relies on ethically debated, expensive and time consuming in vivo experiments, which are unsuitable for high-throughput toxicity screening. There is thus a clear need for a rapid in vitro screening strategy that is preferably based on human-derived neurons to circumvent interspecies translation. Recent availability of commercially obtainable human induced pluripotent stem cell (hiPSC)-derived neurons and astrocytes holds great promise in assisting the transition from the current standard of rat primary cortical cultures to an animal-free alternative...
June 14, 2018: Neurotoxicology
Shimaa M Azmy, Mai A Abd El Fattah, Sahar S Abd El-Rahman, Somia A Nada, Omar M E Abdel Salam, Mohammed F El-Yamany, Noha N Nassar
Nicotine and tramadol concomitant drug dependence pose increasing social, economic as well as public threats. Accordingly, the present study investigated neurochemical, neurobehavioral and neuropathological changes in the brain subsequent to the interaction of nicotine and tramadol. To this end, tramadol (20 mg/kg, i.p) and nicotine (0.25 mg/kg, i.p) were administrated to male albino mice once daily for 30 days. Consequent to microglial activation, nicotine exacerbated oxidative/nitrosative stress induced by tramadol as manifest by the step-up in thiobarbituric acid reactive substances and nitric oxide subsequent to the enhanced levels of neuronal and inducible nitric oxide synthases; paralleled by decreased non-protein sulfhydryls...
June 12, 2018: Neurotoxicology
Alison Cartereau, Jean-Noël Houchat, Safa Mannai, Marie Varloud, Hamadi Karembé, Jérôme Graton, Jean-Yves Le Questel, Steeve H Thany
Insect resistance mechanisms against pesticides lead to the development and the search of new pesticide combinations in order to delay the resistance. The combination of neonicotinoids with pyrethroids was currently proposed but the mode of action of these compounds at synaptic and extrasynaptic levels needs to be further explored. In the present study, we evaluated the effect of the combination of two insecticides, permethrin and dinotefuran, on cockroach cholinergic synaptic transmission and on isolated cell bodies...
June 8, 2018: Neurotoxicology
Emilio Fernández-Espejo, Cristian Bis-Humbert
3-iodo-L-tyrosine might play a role in Parkinson's disease since this molecule is able, at high concentration, to inhibit tyrosine-hydroxylase activity, the rate-limiting enzyme in dopamine biosynthesis. The possible Parkinson-like effects of 3-iodo-L-tyrosine were tested on three experimental approaches in mice: cultured substantia nigra neurons, the enteric nervous system of the jejunum after intra-peritoneal infusions, and the nigrostriatal system following unilateral intrabrain injections. 3-iodo-L-tyrosine, a physiological molecule, was used at concentrations higher than its serum levels in humans...
June 6, 2018: Neurotoxicology
So Young Kim, Jin Ki Kim, Byeong-Gon Kim, An-Soo Jang, Seung Ha Oh, Jun Ho Lee, Myung-Whan Seo, Moo Kyun Park
Little is known regarding the adverse effects of chronic particulate matter (PM) inhalation on the central nervous system (CNS). The present study aimed to examine how PM exposure impacts on oxidative stress and inflammatory processes, as well as the expression of interneurons and perineuronal nets (PNNs) in the CNS. BALB/c mice (6-week-old females, n = 32) were exposed to 1 to 5 μm size diesel-extracted particles (DEPs) (100 µg/m3 , 5 d/week, 5 h/day) and categorized into the following four groups: 1) 4-week DEP (n = 8); 2) 4-week control (n = 8), 3) 8-week DEP (n = 8); and 4) 8-week control (n = 8)...
June 4, 2018: Neurotoxicology
Angelo Nicolosi, Laura Cardoit, Pierrick Pasquereau, Christèle Jaillet, Muriel Thoby-Brisson, Laurent Juvin, Didier Morin
Due to their extremely small size that gives them unique physicochemical properties, nanoparticles (NPs) are used in the production of everyday materials. However, NPs can accumulate in body organs and could cause various diseases. Moreover, NPs that cross biological membranes such as the blood-brain barrier can aggregate in the brain and potentially produce neuronal damage. Although studies have reported the effects of diverse NPs on the bioelectrical properties of individual neurons, their potential influences on the operation of whole neuronal networks have not been documented...
May 31, 2018: Neurotoxicology
Souvarish Sarkar, Emir Malovic, Deeksha Sarda, Vivek Lawana, Dharmin Rokad, Huajun Jin, Vellareddy Anantharam, Arthi Kanthasamy, Anumantha G Kanthasamy
Microglia are the first responders of the central nervous system, acting as the key modulators of neuroinflammation observed during neurotoxic insults as well as in the pathophysiology of several neurodegenerative disorders including Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD). The number of publications on microglia has increased steadily throughout the past decade because of immense interests in the neuroinflammation that precedes the neurodegenerative process. To study microglial biology and its role in modulating neuroinflammation, immortalized microglial cell lines derived from mice, rats, and humans have been developed...
May 30, 2018: Neurotoxicology
Peter A Noshy, Mohamed A Elhady, Abdel Azeim A Khalaf, Mervat M Kamel, Eman I Hassanen
Propiconazole (PCZ) is a triazole fungicide extensively used in agriculture. Carvacrol (CAR) is a naturally occurring phenolic monoterpene which has various biological and pharmacological effects. The present study was designed to investigate the neurobehavioral toxic effects of PCZ in albino rats and to evaluate the ameliorative role of CAR against such toxic effects. Sixty adult male rats were used in this investigation; they were randomly and equally divided into 4 groups: control group, PCZ group, CAR group and PCZ + CAR group...
May 28, 2018: Neurotoxicology
Chloé Cartier, Charline Warembourg, Christine Monfort, Florence Rouget, Gwendolina Limon, Gaël Durand, Sylvaine Cordier, Dave Saint-Amour, Cécile Chevrier
Human exposure to organophosphate pesticides (OP) is widespread. Several studies suggest that OP prenatal exposure alters the development of cognitive and behavioural functions in children, but the effects of OP prenatal exposure on child sensory functions are largely unknown. The aim of the study was to evaluate the association between OP prenatal exposure and visual processing in school-aged children from the mother-child PELAGIE cohort (France). OP biomarkers of exposure were measured in maternal urine samples at the beginning of pregnancy...
May 24, 2018: Neurotoxicology
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