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Neurotoxicity Research

Juan Andrés Abin-Carriquiry, Marcela Martínez-Busi, Martín Galvalisi, Manuel Minteguiaga, José Pedro Prieto, María Cecilia Scorza
Adulteration is a common practice in the illicit drugs market, but the psychoactive and toxic effects provided by adulterants are clinically underestimated. Coca-paste (CP) is a smokable form of cocaine which has an extremely high abuse liability. CP seized samples are sold adulterated; however, qualitative and quantitative data of CP adulteration in forensic literature is still scarce. Besides, it is unknown if adulterants remain stable when CP is heated. This study was designed to report the chemical content of an extensive series of CP seized samples and to demonstrate the stability (i...
March 13, 2018: Neurotoxicity Research
Ewelina Bator, Joachim Latusz, Urszula Głowacka, Aleksandra Radaszkiewicz, Kinga Mudlaff, Marzena Maćkowiak
Social isolation (SI) during adolescence may induce schizophrenia-like behavior. In the present study, we investigated whether adolescent SI might affect the development of schizophrenia-like behavior in the MAM-E17 neurodevelopmental model of schizophrenia. Rats were socially isolated for 10 days during adolescence (postnatal days (P) 30-40), followed by resocialization until late adolescence (P45-P48) or early adulthood (P70-P75); behavioral and neurochemical studies were performed at these ages. The behavioral studies analyzed locomotor activity, social interaction, recognition memory, and sensorimotor gating; GAD65 and GAD67 protein levels were measured in the prefrontal cortex...
March 13, 2018: Neurotoxicity Research
N Khodaie, N Tajuddin, R M Mitchell, E J Neafsey, M A Collins
Preconditioning brain cultures with moderate concentrations of ethanol (EtOH) or trans-resveratrol (RES), key red wine constituents, can prevent amyloid-β (Aβ) neurotoxicity. Past studies have indicated that moderate EtOH activates synaptic N-methyl-D-aspartate receptors (NMDAR) that, in part, signal via protein kinase C (PKC) to increase protective antioxidant proteins such as peroxiredoxin-2 (Prx2). RES preconditioning also is reported to involve NMDAR and PKC. However, although moderate, the EtOH and RES concentrations used have been noticeably above circulating levels from two glasses of wine, a daily intake linked to reduced risk of cognitive decline among older social drinkers...
March 12, 2018: Neurotoxicity Research
Dinesh Kumar Verma, Sonam Gupta, Joyshree Biswas, Neeraj Joshi, K Sivarama Raju, Mu Wahajuddin, Sarika Singh
Piracetam, a nootropic drug, has been clinically used for decades; however, its mechanism of action still remains enigmatic. The present study was undertaken to evaluate the role of mitochondrion-specific factors of caspase-independent pathway like apoptotic-inducing factor (AIF) and endonuclease-G (endo-G) in piracetam-induced neuroprotection. N2A cells treated with lipopolysaccharide (LPS) exhibited significant cytotoxicity, impaired mitochondrial activity, and reactive oxygen species generation which was significantly attenuated with piracetam co-treatment...
March 12, 2018: Neurotoxicity Research
MingXia Yu, Tao Cao, Dan Yu, Fusheng Huang
Genetic susceptibility to high mercury body burden has been suggested as an autism risk factor in children. Metallothionein III (MT3) is the brain-specific form of the metallothionein family, which plays a key role in metal metabolism. We therefore looked for genetic variations in the MT3 gene that might increase the predisposition to autism. DNA was extracted from 132 autistic children and 132 age and gender-matched unrelated controls. All the samples were analyzed for nine single nucleotide polymorphisms (SNPs) with minor allele frequency > 10% in the MT3 gene...
March 9, 2018: Neurotoxicity Research
Mohammad Javad Ebrahimi, Abbas Aliaghaei, Mahdi Eskandarian Boroujeni, Fariba Khodagholi, Gholamhoussein Meftahi, Mohammad Amin Abdollahifar, Houssein Ahmadi, Samira Danyali, Mahtab Daftari, Yousef Sadeghi
Huntington disease (HD) is an inherited disorder hallmarked by progressive deterioration of specific neurons, followed by movement and cognitive anomalies. Cell therapy approaches in neurodegenerative conditions have concentrated on the replenishment of lost/dying neurons with functional ones. Multipotent mesenchymal stem cells (MSCs) have been represented as a potential remedy for HD. In this study, we evaluated the in vitro and in vivo efficacy of umbilical cord matrix stem cells (UCMSCs) and their paracrine effect against oxidative stress with a specific focus on HD...
March 8, 2018: Neurotoxicity Research
Cybelle Façanha Barreto Medeiros-Linard, Belmira Lara da Silveira Andrade-da-Costa, Ricielle Lopes Augusto, Adriana Sereniki, Maria Teresa Sales Trevisan, Renata de Cássia Ribas Perreira, Francisco Thiago Correia de Souza, Glauber Ruda Feitoza Braz, Claudia Jacques Lagranha, Ivone Antônia de Souza, Almir Gonçalves Wanderley, Soraya S Smailli, Simone Sette Lopes Lafayette
Anacardic acids (AAs) are alkyl phenols mainly presenting in cashew nuts. The antioxidant effects of these compounds have been an area of interest in recent research, with findings suggesting potential therapeutic use for certain diseases. Nevertheless, none of these studies were performed in order to test the hypothesis of whether anacardic acids are capable of preventing behavioral changes and oxidative stress induced by the pesticide rotenone in experimental model of Parkinson's disease. In our research, adult male rats were treated orally with AAs (1, 3, 10, 25, 50, or 100 mg/kg/day) 1 h before rotenone (3 mg/kg; s...
March 8, 2018: Neurotoxicity Research
Wenji He, Xinyu Yan, Sanqiang Pan
Amphetamine (AMPH) abuse can influence neuropsychiatric disorders and cell apoptosis by interfering with the protein kinase B/ glycogen synthase kinase 3 beta (AKT/GSK3β) pathway. However, the mechanisms underlying this regulation are poorly understood. Using PC12 cells, we found that AMPH inhibited AKT and GSK-3β phosphorylation levels and increased total GSK-3β levels. Furthermore, AMPH caused an increase in the activity of protein phosphatase 2 (PP2A), a signaling protein upstream of AKT, which in turn inhibited phosphorylated AKT levels...
March 6, 2018: Neurotoxicity Research
Marcos Roberto de Oliveira, Flávia Bittencourt Brasil, Cristina Ribas Fürstenau
Sulforaphane (SFN), an isothiocyanate obtained from cruciferous vegetables, exerts antioxidant, antiapoptotic, and antitumor activities in different cell types. Moreover, SFN has been viewed as an anti-inflammatory agent. Nonetheless, the mechanism underlying the ability of SFN in modulating the immune response in mammalian cells is not completely understood yet. Therefore, we investigated here whether and how SFN would be effective in preventing inflammation induced by a pro-oxidant agent (hydrogen peroxide, H2 O2 ) in the human neuroblastoma SH-SY5Y cells...
February 23, 2018: Neurotoxicity Research
Natalia Moreno-Galarza, Liliana Mendieta, Victoria Palafox-Sánchez, Mireia Herrando-Grabulosa, Carles Gil, Daniel I Limón, José Aguilera
Several studies have shown that intrastriatal application of 1-methyl-4-phenylpyridinium (MPP+ ) produces similar biochemical changes in rat to those seen in Parkinson's disease (PD), such as dopaminergic terminal degeneration and consequent appearance of motor deficits, making the MPP+ lesion a widely used model of parkinsonism in rodents. Previous results from our group have shown a neuroprotective effect of the carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) under different types of stress...
February 19, 2018: Neurotoxicity Research
Yirong Xu, Huifang Zhang, Baolong Pan, Shuhui Zhang, Shan Wang, Qiao Niu
Aluminum (Al) is an environmental neurotoxicant with a wide exposure, but the molecular mechanism underlying its toxicity remains unclear. We used RNA sequencing (RNA-seq) in the hippocampus of Al-treated rats to identify 96 upregulated and 652 downregulated mRNAs, and 37 dysregulated long non-coding (lnc)RNAs. Gene ontology analysis showed that dysregulated genes were involved in glial cell differentiation, neural transmission, and vesicle trafficking. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed clustering of differentially expressed mRNAs and lncRNA target genes in several pathways, including the "adenosine monophosphate-activated protein kinase signaling pathway," "extracellular matrix receptor interaction," "the phosphatidylinositol 3 kinase-protein kinase B signaling pathway," and "focal adhesion" signaling pathway...
February 19, 2018: Neurotoxicity Research
Nutnicha Tantarungsee, Waranurin Yisarakun, Thananya Thongtan, Laddawan Lalert, Sirinapa Srikam, Preecha Reuangwechvorachai, Praewphan Ingruanglert, Supang Maneesri-le Grand
The present study aimed to investigate the effect of APAP treatment on the expression of pro-inflammatory cytokines in the astrocytes. The mouse astrocyte cells (C8-D1A) were treated with APAP at the concentration of 100 μM for 24 h, 16 and 28 days. The expressions of pro-inflammatory cytokines and NF-kB were determined using western blot analysis. Furthermore, the expression and localization of phosphorylation of NF-kB were detected by immunohistochemical and immunofluorescent analysis. The ultrastructure of C8-D1A cells was as well monitored...
February 14, 2018: Neurotoxicity Research
Katarzyna Socała, Dorota Nieoczym, Mateusz Pieróg, Elżbieta Wyska, Małgorzata Szafarz, Urszula Doboszewska, Piotr Wlaź
Tadalafil, a selective phosphodiesterase type 5 inhibitor, is a long-acting oral agent for the treatment of erectile dysfunction of multiple etiologies. Although generalized tonic-clonic seizures were reported in a healthy man after taking tadalafil, the influence of tadalafil on seizure susceptibility has not been studied so far. Therefore, the aim of the present study was to investigate the effect of tadalafil on seizure threshold as well as on the activity of some first- and second-generation antiepileptic drugs in three acute seizure tests in mice...
February 9, 2018: Neurotoxicity Research
Arnold Gutierrez, Michael T Williams, Charles V Vorhees
Methamphetamine (MA) alters dopamine markers and cognitive function in heavy users. In rodents, there are MA dosing regimens that induce concordant effects using repeated administration at spaced intervals. These regimens are effective but complicate experiments designed to disentangle the effects of the drug on different brain regions in relation to their cognitive effects because of treatment spacing. In an effort to simplify the model, we tested whether a single dose of MA could induce the same monoamine and cognitive effects as multiple, spaced dosing without affecting survival...
February 9, 2018: Neurotoxicity Research
Sugumar Mani, Sathiya Sekar, Rajamani Barathidasan, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Murugan Sevanan, Saravana Babu Chidambaram, Musthafa Mohamed Essa, Gilles J Guillemin, Meena Kishore Sakharkar
The present study was designed to ascertain the role of naringenin (NGN), a citrus fruit flavanone, against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced α-synuclein (SYN) pathology and neuroinflammation in a mouse model. NGN was administered to C57BL/6J mice once a day for 5 consecutive days prior to the MPTP intoxication. On day 5, 40-50 min after the NGN or vehicle administration, MPTP was injected in two divided doses (2× 40 mg/kg, i.p. at 16 h apart). The animals were observed for motor functions 48 h after the first MPTP injection...
February 9, 2018: Neurotoxicity Research
Xi Chen, Xue Zhou, Lu Yang, Xu Miao, Di-Han Lu, Xiao-Yu Yang, Zhi-Bin Zhou, Wen-Bin Kang, Ke-Yu Chen, Li-Hua Zhou, Xia Feng
The increasing usage of general anesthetics on young children and infants has drawn extensive attention to the effects of these drugs on cognitive function later in life. Recent animal studies have revealed improvement in hippocampus-dependent performance after lower concentrations of sevoflurane exposure. However, the long-term effects of low-dose sevoflurane on the developing brain remain elusive. On postnatal day (P) 7, rats were treated with 1.2% sevoflurane (1.2% sevo group), 2.4% sevoflurane (2.4% sevo group), and air control (C group) for 6 h...
February 9, 2018: Neurotoxicity Research
Alan R Hipkiss
There is a strong association between neurodegeneration and protein glycation; possible origins of neurotoxic glycated protein, also called glycotoxins, include (i) diet (i.e., proteins cooked at high temperatures), (ii) protein glycation in the gut, and (iii) intracellular reaction of proteins with deleterious aldehydes, especially methylglyoxal (MG). It is likely that excessive glycolysis provokes increased generation of dihydroxyacetone phosphate which decomposes into MG due to activity-induced deamidation of certain asparagine residues in the glycolytic enzyme triose-phosphate isomerase (TPI)...
February 7, 2018: Neurotoxicity Research
Stefanie Endesfelder, Ulrike Weichelt, Cornelia Schiller, Katja Winter, Clarissa von Haefen, Christoph Bührer
In preterm infants, phenobarbital is the first-line antiepileptic drug for neonatal seizures while caffeine is used for the treatment of apnea. Data from experimental animals suggest that phenobarbital and other anticonvulsants are toxic for the developing brain, while neuroprotective effects have been reported for caffeine both in newborn rodents and preterm human infants. To characterize the interaction of phenobarbital and caffeine in the hippocampus of the developing rodent brain, we examined the effects of both drugs given separately or together on postnatal neurogenesis after administration to neonatal rats throughout postnatal day (P) 4 to P6...
February 7, 2018: Neurotoxicity Research
Lara M Gomes, Giselli Scaini, Milena Carvalho-Silva, Maria L Gomes, Fernanda Malgarin, Luiza W Kist, Maurício R Bogo, Eduardo Pacheco Rico, Alexandra I Zugno, Pedro F P Deroza, Gislaine Z Réus, Airam B de Moura, João Quevedo, Gustavo C Ferreira, Patrícia F Schuck, Emilio L Streck
Tyrosinemia type II is an inborn error of metabolism caused by a deficiency in the activity of the enzyme tyrosine aminotransferase, leading to tyrosine accumulation in the body. Although the mechanisms involved are still poorly understood, several studies have showed that higher levels of tyrosine are related to oxidative stress and therefore may affect the cholinergic system. Thus, the aim of this study was to investigate the effects of chronic administration of L-tyrosine on choline acetyltransferase activity (ChAT) and acetylcholinesterase (AChE) in the brain of rats...
February 7, 2018: Neurotoxicity Research
Rafael Teixeira Ribeiro, Ângela Zanatta, Alexandre Umpierrez Amaral, Guilhian Leipnitz, Francine Hehn de Oliveira, Bianca Seminotti, Moacir Wajner
Tissue accumulation of L-2-hydroxyglutaric acid (L-2-HG) is the biochemical hallmark of L-2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic inherited disease characterized by neurological symptoms and brain white matter abnormalities whose pathogenesis is not yet well established. L-2-HG was intracerebrally administered to rat pups at postnatal day 1 (P1) to induce a rise of L-2-HG levels in the central nervous system (CNS). Thereafter, we investigated whether L-2-HG in vivo administration could disturb redox homeostasis and induce brain histopathological alterations in the cerebral cortex and striatum of neonatal rats...
February 6, 2018: Neurotoxicity Research
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