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Neurotoxicity Research

Camila Mouhape, Gustavo Costa, Margot Ferreira, Juan Andrés Abin-Carriquiry, Federico Dajas, Giselle Prunell
Parkinson's disease (PD) is characterized by the degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). Clinical and experimental evidence suggest that the activation of the nicotinic acetylcholine receptor (nAChR) could be protective for PD. In this study, we investigated the neuroprotective capacity of nicotine in a rat PD model. Considering that iron metabolism has been implicated in PD pathophysiology and nicotine has been described to chelate this metal, we also studied the effect of nicotine on the cellular labile iron pool (LIP) levels...
July 13, 2018: Neurotoxicity Research
Sathiya Sekar, Sugumar Mani, Barathidasan Rajamani, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Abid Bhat, Bipul Ray, Musthafa Mohamed Essa, Gilles J Guillemin, Saravana Babu Chidambaram
Many studies reported the neuroprotective effects of angiotensin II type 1 receptor (AT1R) antagonists in Parkinson's disease (PD). However, the role of AT1R blockade on astroglial, in turn, dopaminergic functions in chronic PD is still to be studied. In the present study, telmisartan (TEL; 3 and 10 mg/kg/day; p.o), was used to study the effects AT1R blockade on astrocytic and dopaminergic functions in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinsonism (250 mg/kg, i...
July 13, 2018: Neurotoxicity Research
Olfa Rebai, Mohamed Amri
In the CNS, including the optic nerve, oligodendrocytes play a critical role in the myelination of axons. Oligodendrocytes are exceptionally sensitive to insults to the CNS, such as injury, ischemia, or inflammation, which result in the loss of oligodendrocytes and myelin and eventually secondary axon degeneration. Oligodendrocytes are sensitive to excitotoxic insults mediated by overactivation of their AMPA ionotropic glutamate receptors. Phenolic compounds, which are widely distributed in fruits and vegetables, received the great attention of scientists due to their antioxidant activities and free radical scavenging abilities...
July 13, 2018: Neurotoxicity Research
Tuane Bazanella Sampaio, Laíse Figueiredo de Oliveira, Leandra Celso Constantino, Ana Paula Costa, Gabriela Godoy Poluceno, Wagner Carbolin Martins, Tharine Dal-Cim, Karen Andrinéia de Oliveira, Fabiana Kalyne Ludka, Rui Daniel Prediger, Carla Inês Tasca, Frederico C Pereira
The neonatal exposure to general anesthetics has been associated with neuronal apoptosis and dendritic spines morphologic changes in the developing brain. Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used in pediatric patients to induce general anesthesia, analgesia, and perioperative sedation. In the present study, we investigated short- and long-term effects of a single ketamine (20 mg/kg, s.c.) neonatal exposure at postnatal day 7 in rats on the hippocampal and frontal cortical cellular viability...
July 2, 2018: Neurotoxicity Research
Xiao-Ling Zhong, Jie-Qiong Li, Li Sun, Ya-Qing Li, Hui-Fu Wang, Xi-Peng Cao, Chen-Chen Tan, Ling Wang, Lan Tan, Jin-Tai Yu
α-Synuclein is a 140-amino acid protein produced predominantly by neurons in the brain which plays a role in the regulation of neurotransmitter release, synaptic function, and plasticity, thus making it the focus in understanding the etiology of a group of neurodegenerative diseases. We conducted genome-wide association studies (GWAS) of α-synuclein levels in cerebrospinal fluid (CSF) with 209 non-Hispanic white participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1) cohort using a linear regression model to identify novel variants associated with α-synuclein concentration...
June 29, 2018: Neurotoxicity Research
Carolyne Lespay-Rebolledo, Ronald Perez-Lobos, Andrea Tapia-Bustos, Valentina Vio, Paola Morales, Mario Herrera-Marschitz
The present report evaluates the effect of global perinatal asphyxia on several parameters of oxidative stress and cell viability in rat brain tissue sampled at an extended neonatal period up to 14 days, a period characterised by intensive neuritogenesis, synaptogenesis, synaptic consolidation, pruning and delayed cell death. Perinatal asphyxia was induced by immersing foetus-containing uterine horns removed by a caesarean section from on term rat dams into a water bath at 37 °C for 21 min. Asphyxia-exposed and sibling caesarean-delivered foetuses were manually resucitated and nurtured by surrogate dams for 1 to 14 postnatal (P) days...
June 29, 2018: Neurotoxicity Research
Jakub Wojcieszak, Dariusz Andrzejczak, Marta Kedzierska, Katarzyna Milowska, Jolanta B Zawilska
Pyrovalerone derivatives (α-pyrrolidinophenones) form a branch of synthetic cathinones, a second most prominent group of novel psychoactive substances. Although the toxicity of 3,4-MDPV, a progenitor of the α-pyrrolidinophenones, is well described, little is known of the potential cytotoxicity of the new members of this group entering the recreational drug market each year. The present study assesses the cytotoxicity of members of the α-pyrrolidinophenone group, i.e., α-PVP, its longer side-chain derivatives PV8 and PV9, and their 4-fluoro- and 4-methoxy-analogs, against model cell lines for the nervous system (SH-SY5Y), liver (Hep G2) and upper airway epithelium (RPMI 2650), and cardiomyocytes (H9C2(2-1))...
June 27, 2018: Neurotoxicity Research
Noelia Granado, Sara Ares-Santos, Yousef Tizabi, Rosario Moratalla
Methamphetamine (METH), an amphetamine derivate, may increase the risk of developing Parkinson's disease (PD). Human and animal studies have shown that METH produces persistent dopaminergic neurotoxicity in the nigrostriatal pathway, despite initial partial recovery. To determine the processes leading to early compensation, we studied the detailed morphology and distribution of tyrosine hydroxylase immunoreactive fibers (TH-ir) classified by their thickness (types I-IV) before and after METH. Applying three established neurotoxic regimens of METH: single high dose (1 × 30 mg/kg), multiple lower doses (3 × 5 mg/kg) or (3 × 10 mg/kg), we show that METH primarily damages type I fibers (the thinner ones), and to a much lesser extend types II-IV fibers including sterile axons...
June 22, 2018: Neurotoxicity Research
Teresa Coccini, Sarah Vecchio, Marta Crevani, Uliana De Simone
3,4-Methylenedioxypyrovalerone (MDPV), one of the most commonly abused synthetic cathinones, has caused several intoxications and deaths despite its short presence on the market. Apart from its effects on the monoamine systems in the brain, recent in vitro investigations have revealed cytotoxicity. In this study, the effects of increasing concentrations (10-1000 μM) of 3,4-Catechol-PV, one of major MDPV metabolites, on cell viability, morphology, and apoptosis have been evaluated after acute exposure (24-48 h) in human neuroblastoma SH-SY5Y cells-undifferentiated and differentiated to a more mature neuronal-like phenotype...
June 22, 2018: Neurotoxicity Research
Aline Colonnello, Ilan Kotlar, María Eduarda de Lima, Alma Ortíz-Plata, Rodolfo García-Contreras, Félix Alexandre Antunes Soares, Michael Aschner, Abel Santamaría
Molecules exhibiting antioxidant, neuroprotective, and regulatory properties inherent to natural products consumed by humans are gaining attention in biomedical research. Ferulic acid (FA) is a phenolic compound possessing antioxidant and cytoprotective properties. It is found in several vegetables, including sugarcane, where it serves as the main antioxidant component. Here, we compared the antioxidant and cytoprotective effects of FA with those of the total sugarcane aqueous extract (SCAE). Specifically, we assessed biochemical markers of cell dysfunction in rat cortical brain slices and markers of physiological stress in Caenorhabditis elegans upon exposure to toxins evoking different mechanisms of neurotoxicity, including direct oxidative stress and/or excitotoxicity...
June 15, 2018: Neurotoxicity Research
Manish Kumar Tripathi, Charul Rajput, Saumya Mishra, Mohd Sami Ur Rasheed, Mahendra Pratap Singh
Homeostatic regulation of class II programmed cell death/autophagy for the degradation and elimination of substandard organelles and defective proteins is decisive for the survival of dopaminergic neurons. Chaperone-mediated autophagy (CMA), one of the most highly dedicated self-sacrificing events, is accountable for the partial elimination of redundant soluble cytoplasmic proteins in Parkinson's disease (PD). CMA is characterized by the selective delivery of superfluous protein containing lysine-phenylalanine-glutamate-arginine-glutamine (KFERQ)/KFERQ-like motif to the lysosome through molecular chaperones, such as heat shock cognate-70 (Hsc-70)...
June 11, 2018: Neurotoxicity Research
Maciej Florczyk, Paweł Brzuzan, Alicja Łakomiak, Ewa Jakimiuk, Maciej Woźny
Microcystin-LR (MC-LR) is a potent hepatotoxin that has also been pointed out of causing neurotoxicity, but the exact mechanisms of action still remain ambiguous and need to be elucidated. Data from studies on mammals show that pathology of astrocyte cells points to perturbations of microRNA signaling. Glial fibrillary acidic protein (GFAP), a neuronal cell/astrocyte-specific protein, and a microRNA-124-3p (MiR124-3p) are among putative triggers and regulators of neuronal cell/astrocyte reactivity. In the present study on whitefish (Coregonus lavaretus), we found that gfap mRNA contains a putative target site for MIR124-3p, to potentially affect its expression changes...
June 7, 2018: Neurotoxicity Research
Tanara V Peres, Leticia P Arantes, Mahfuzur R Miah, Julia Bornhorst, Tanja Schwerdtle, Aaron B Bowman, Rodrigo B Leal, Michael Aschner
Excessive levels of the essential metal manganese (Mn) may cause a syndrome similar to Parkinson's disease. The model organism Caenorhabditis elegans mimics some of Mn effects in mammals, including dopaminergic neurodegeneration, oxidative stress, and increased levels of AKT. The evolutionarily conserved insulin/insulin-like growth factor-1 signaling pathway (IIS) modulates worm longevity, metabolism, and antioxidant responses by antagonizing the transcription factors DAF-16/FOXO and SKN-1/Nrf-2. AKT-1, AKT-2, and SGK-1 act upstream of these transcription factors...
June 7, 2018: Neurotoxicity Research
Mona Amiri, Nady Braidy, Malihe Aminzadeh
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive loss of cholinergic neurons. Amyloid beta is a misfolded protein that represents one of the key pathological hallmarks of AD. Numerous studies have shown that Aβ1-42 induces oxidative damage, neuroinflammation, and apoptosis, leading to cognitive decline in AD. Recently, fibroblast growth factor 21 (FGF21) has been suggested to be a potential regulator of oxidative stress in mammalian cells. FGF21 has been shown to improve insulin sensitivity, reduce hyperglycemia, increase adipose tissue glucose uptake and lipolysis, and decrease body fat and weight loss by enhancing energy expenditure...
June 5, 2018: Neurotoxicity Research
Adi Pinkas, Kun He Lee, Pan Chen, Michael Aschner
The receptor for advanced glycation products (RAGE) is a cell surface, multi-ligand receptor belonging to the immunoglobulin superfamily; this receptor is implicated in a variety of maladies, via inflammatory pathways and induction of oxidative stress. Currently, RAGE is being studied using a limited number of mammalian in vivo, and some complementary in vitro, models. Here, we present a Caenorhabditis elegans model for the study of RAGE-related pathology: a transgenic strain, expressing RAGE in all neurons, was generated and subsequently tested behaviorally, developmentally, and morphologically...
June 4, 2018: Neurotoxicity Research
Dirleise Colle, Marcelo Farina, Sandra Ceccatelli, Marilena Raciti
Pesticide exposure has been linked to the pathogenesis of neurodevelopmental and neurodegenerative disorders including autism spectrum disorders, attention deficit/hyperactivity, and Parkinson's disease (PD). Developmental exposure to pesticides, even at low concentrations not harmful for the adult brain, can lead to neuronal loss and functional deficits. It has been shown that prenatal or early postnatal exposure to the herbicide paraquat (PQ) and the fungicide maneb (MB), alone or in combination, causes permanent toxicity in the nigrostriatal dopamine system, supporting the idea that early exposure to these pesticides may contribute to the pathophysiology of PD...
June 1, 2018: Neurotoxicity Research
Daniel A Martinez-Perez, Marlene Jimenez-Del-Rio, Carlos Velez-Pardo
The original version of this article contained mistakes, and the authors would like to publish this erratum. The "Acknowledgement" section was not included in the aforementioned manuscript.
June 1, 2018: Neurotoxicity Research
Marissa Giovanna Schamne, Josiel Mileno Mack, Morgana Moretti, Filipe Carvalho Matheus, Roger Walz, Laurence Lanfumey, Rui Daniel Prediger
Depression is a highly prevalent and debilitating non-motor symptom observed during the early stages of Parkinson's disease (PD). Although PD prevalence is higher in men, the depressive symptoms in PD are more common in women. Therefore, the aim of this study was to investigate the development of anhedonic- and depressive-like behaviors in male and female mice and the potential mechanisms related to depressive symptoms in an experimental model of PD. Young adult male and female C57BL/6 mice (3 months old) received a single intranasal (i...
May 28, 2018: Neurotoxicity Research
Bruk Getachew, Tamaro Hudson, Thomas Heinbockel, Antonei B Csoka, Yousef Tizabi
Ethanol (EtOH) is one of the most frequently abused drugs with heavy health, economic, and societal burdens. Although moderate to low EtOH may have some neuroprotective effects, heavy EtOH consumption associated with high blood alcohol level (BAL) can be quite detrimental. The brain is particularly vulnerable to the damaging effects of high BAL, leading to neuronal loss, cognitive, and behavioral deficits. Although the exact causes of these detriments are not fully elucidated, it is believed that damage to the cholinergic system is at least partially responsible for the cognitive impairment...
May 26, 2018: Neurotoxicity Research
Beata Bystrowska, Małgorzata Frankowska, Irena Smaga, Lucyna Pomierny-Chamioło, Małgorzata Filip
The aim of this study was to evaluate changes in the expression of cannabinoid type 1 (CB1) and 2 (CB2) receptor proteins in several brain regions in rats undergoing cocaine self-administration and extinction training. We used a triad-yoked procedure to distinguish between the motivational and pharmacological effects of cocaine. Using immunohistochemistry, we observed a significant decrease in CB1 receptor expression in the prefrontal cortex, dorsal striatum, and the basolateral and basomedial amygdala following cocaine (0...
May 12, 2018: Neurotoxicity Research
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