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Neurotoxicity Research

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https://www.readbyqxmd.com/read/29344837/evaluation-of-the-profile-and-mechanism-of-neurotoxicity-of-water-soluble-cu-p-4-pf6-and-au-p-4-pf6-p-thp-or-pta-anticancer-complexes
#1
C Ceresa, G Nicolini, S Semperboni, V Gandin, M Monfrini, F Avezza, P Alberti, A Bravin, M Pellei, C Santini, Guido Cavaletti
[Cu(thp)4]PF6, [Cu(PTA)4]PF6, [Au(thp)4]PF6 and [Au(PTA)4]PF6 are phosphane (thp = tris(hydroxymethyl)phosphane; PTA = 1,3,5-triaza-7-phosphaadamantane) copper(I) and gold(I) water-soluble complexes characterized by high anticancer activity in a wide range of solid tumors, often able to overcome drug resistance of platinum-based compounds. For these reasons, they have been proposed as a valid alternative to platinum-based chemotherapeutic drugs (e.g., cisplatin and oxaliplatin). In vitro experiments performed on organotypic cultures of dorsal root ganglia (DRG) from 15-day-old rat embryos revealed that copper-based compounds were not neurotoxic even at concentrations higher than the IC50 obtained in human cancer cells while [Au(PTA)4]PF6 was neurotoxic at lower concentration than IC50 in cancer cell lines...
January 17, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29340871/neurotoxicity-of-prosopis-juliflora-from-natural-poisoning-to-mechanism-of-action-of-its-piperidine-alkaloids
#2
Victor Diogenes Amaral da Silva, André Mario Mendes da Silva, Juliana Helena Castro E Silva, Silvia Lima Costa
Prosopis juliflora was introduced in northeastern Brazil in the 1940s, and since then, it has been available as an alternative for animal nutrition. However, the consumption of P. juliflora as main or sole source of food causes an illness in animals known locally as "cara torta" disease. Cattle and goats experimentally intoxicated presents neurotoxic damage in the central nervous system. Histologic lesions were mainly characterized by vacuolation and loss of neurons in trigeminal motor nuclei. Furthermore, mitochondrial damage in neurons and gliosis was reported in trigeminal nuclei of intoxicated cattle...
January 16, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29327213/add-on-treatment-with-curcumin-has-antidepressive-effects-in-thai-patients-with-major-depression-results-of-a-randomized-double-blind-placebo-controlled-study
#3
Buranee Kanchanatawan, Sookjaroen Tangwongchai, Atapol Sughondhabhirom, Siriluck Suppapitiporn, Solaphat Hemrunrojn, André F Carvalho, Michael Maes
Activation of immune-inflammatory and oxidative-nitrosative (IO&NS) stress pathways plays a role in major depression (MDD). Evidence suggests that curcumin (500-1000 mg/day), a polyphenol with strong anti-IO&NS properties, may have efficacy either as monotherapy or as an adjunctive treatment for depression. Further controlled trials with extended treatment periods (> 8 weeks) and higher curcumin doses are warranted. This 12-week study was carried out to examine the effects of adjunctive curcumin for the treatment of MDD...
January 11, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29313219/neurotoxins-as-preclinical-models-for-parkinson-s-disease
#4
Juan Segura-Aguilar
Translational medicine is one of the major concerns in this century. While significant advances have been made with scientific knowledge, the translation of their promising results has not led to any new therapies. In Parkinson's disease, a long list of clinical studies, based on preclinical models with exogenous neurotoxins, has failed. Therefore, the aim of this opinion paper is to open discussion about preclinical models for Parkinson's disease based on neurotoxins.
January 8, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29313218/thallium-induced-toxicity-in-rat-brain-crude-synaptosomal-mitochondrial-fractions-is-sensitive-to-anti-excitatory-and-antioxidant-agents
#5
Marisol Maya-López, María Verónica Mireles-García, Monserrat Ramírez-Toledo, Ana Laura Colín-González, Sonia Galván-Arzate, Isaac Túnez, Abel Santamaría
The mechanisms by which the heavy metal thallium (Tl+) produces toxicity in the brain remain unclear. Herein, isolated synaptosomal/mitochondrial P2 crude fractions from adult rat brains were exposed to Tl+ (5-250 μM) for 30 min. Three toxic endpoints were evaluated: mitochondrial dysfunction, lipid peroxidation, and Na+/K+-ATPase activity inhibition. Concentration-response curves for two of these endpoints revealed the optimum concentration of Tl+ to induce damage in this preparation, 5 μM. Toxic markers were also estimated in preconditioned synaptosomes incubated in the presence of the N-methyl-D-aspartate receptor antagonist kynurenic acid (KYNA, 50 μM), the cannabinoid receptor agonist WIN 55,212-2 (1 μM), or the antioxidant S-allyl-L-cysteine (SAC, 100 μM)...
January 8, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29313217/temporal-pattern-and-crosstalk-of-necroptosis-markers-with-autophagy-and-apoptosis-associated-proteins-in-ischemic-hippocampus
#6
Fari Ryan, Fariba Khodagholi, Leila Dargahi, Dariush Minai-Tehrani, Abolhassan Ahmadiani
Necroptosis, a novel type of programmed cell death, has been recently implicated as a possible mechanism for cerebral ischemia-reperfusion (I/R) injury. We herein studied time-dependent changes of necroptosis markers along with apoptosis- and autophagy-associated proteins in rat hippocampus at 1, 3, 6, 12, 24, and 48 h after global cerebral I/R injury. Furthermore, to determine the cross talk between autophagy and necroptosis, we examined the effects of pretreatment with bafilomycin-A1 (Baf-A1), as a late-stage autophagy inhibitor, on necroptosis...
January 8, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29302849/low-vs-high-alcohol-central-benefits-vs-detriments
#7
REVIEW
Yousef Tizabi, Bruk Getachew, Clifford L Ferguson, Antonei B Csoka, Karl M Thompson, Alejandra Gomez-Paz, Jana Ruda-Kucerova, Robert E Taylor
The dose-dependent effects of alcohol, where the initial euphoric and stimulant effects initiated by the exposure to low ethanol levels can quickly lead to a deadly consequence are well established. Thus, high blood alcohol concentration (BAC), as seen in alcoholics, can cause significant damage to various organs. At low concentrations (e.g., 10 mg% or lower), however, beneficial effects of alcohol, particularly on cardiovascular function have been reported. Although, the latter assertion has been challenged by recent epidemiological studies, protective effects of low alcohol concentrations in vitro and in vivo relevant to the central nervous system (CNS) is well documented...
January 4, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29297151/liver-x-receptor-agonist-gw3965-regulates-synaptic-function-upon-amyloid-beta-exposure-in-hippocampal-neurons
#8
C Báez-Becerra, F Filipello, A Sandoval-Hernández, H Arboleda, G Arboleda
Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by beta-amyloid (Aβ) accumulation and neurofibrillary tangles formation in the brain which are associated to synaptic deficits and dementia. Liver X receptor (LXR) agonists have been demonstrated to revert of pathologic and cognitive defects in murine models of AD through the regulation of Apolipoprotein E, ATP-Binding Cassette A1 (ABCA1), by dampening neuroinflammation and also by reducing the levels of amyloid-β (Aβ) accumulation in the brain...
January 3, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29294239/km-34-a-novel-antioxidant-compound-protects-against-6-hydroxydopamine-induced-mitochondrial-damage-and-neurotoxicity
#9
Luis Arturo Fonseca-Fonseca, Yanier Nuñez-Figueredo, Jeney Ramírez Sánchez, Maylin Wong Guerra, Estael Ochoa-Rodríguez, Yamila Verdecia-Reyes, René Delgado Hernádez, Noelio J Menezes-Filho, Teresa Cristina Silva Costa, Wagno Alcântara de Santana, Joana L Oliveira, Juan Segura-Aguilar, Victor Diogenes Amaral da Silva, Silva Lima Costa
The etiology of Parkinson's disease is not completely understood and is believed to be multifactorial. Neuronal disorders associated to oxidative stress and mitochondrial dysfunction are widely considered major consequences. The aim of this study was to investigate the effect of the synthetic arylidenmalonate derivative 5-(3,4-dihydroxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (KM-34), in oxidative stress and mitochondrial dysfunction induced by 6-hydroxydopamine (6-OHDA). Pretreatment (2 h) with KM-34 (1 and 10 μM) markedly attenuated 6-OHDA-induced PC12 cell death in a concentration-dependent manner...
January 2, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29294238/effects-of-the-positive-allosteric-modulator-of-metabotropic-glutamate-receptor-5-vu-29-on-impairment-of-novel-object-recognition-induced-by-acute-ethanol-and-ethanol-withdrawal-in-rats
#10
Marta Marszalek-Grabska, Ewa Gibula-Bruzda, Anna Bodzon-Kulakowska, Piotr Suder, Kinga Gawel, Joanna Filarowska, Joanna Listos, Wojciech Danysz, Jolanta H Kotlinska
Glutamate is essential for learning and memory processes, and acute and chronic exposures to ethanol (or protracted abstinence) alter glutamatergic transmission. In the current study, we investigated the effects of VU-29, positive allosteric modulator of metabotropic glutamate 5 (mGlu5) receptor, on the acute ethanol- and ethanol withdrawal-induced impairment of novel object recognition (NOR) task in rats. The influence of VU-29 (30 mg/kg) on memory retrieval was measured (a) at 4-h delay after acute ethanol administration, as well as (b) after acute withdrawal (24 and 48 h) of repeated (2...
January 2, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29285614/the-effects-of-quinine-on-neurophysiological-properties-of-dopaminergic-neurons
#11
Li Zou, Yingchao Xue, Michael Jones, Thomas Heinbockel, Mingyao Ying, Xiping Zhan
Quinine is an antimalarial drug that is toxic to the auditory system by commonly inducing hearing loss and tinnitus, presumably due to its ototoxic effects on disruption of cochlear hair cells and blockade of ion channels of neurons in the auditory system. To a lesser extent, quinine also causes ataxia, tremor, and dystonic reactions. As dopaminergic neurons are implicated to play a role in all of these diseases, we tested the toxicity of quinine on induced dopaminergic (iDA) neurons derived from human pluripotent stem cells (iPSCs) and primary dopaminergic (DA) neurons of substantia nigra from mice brain slices...
December 29, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29273965/effects-of-%C3%AE-7-nicotinic-receptor-activation-on-cell-survival-in-rat-organotypic-hippocampal-slice-cultures
#12
Denise F Happ, R Andrew Tasker
Glutamatergic signaling via N-methyl-D-aspartate receptors (NMDARs) is important for physiological functioning, but can also induce cell death via excitotoxic mechanisms in many neuropathological diseases, such as stroke. Altering the cellular response to excitotoxic insults by modulating the downstream effects of NMDAR activation represents a promising therapeutic approach. For example, α7 nicotinic acetylcholine receptors (α7 nAChRs) signaling has been shown to be able to change NMDA-induced neurotoxicity in some models...
December 22, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29264843/elevated-lipoprotein-a-and-risk-of-poor-functional-outcome-in-chinese-patients-with-ischemic-stroke-and-type-2-diabetes
#13
Haoliang Wang, Jun Zhao, Yongkun Gui, Haiqing Yan, Zhixin Yan, Ping Zhang, Li Liu, Li Chang, Jianlong Zhang
The aim of this study was to evaluate the short-term prognostic value of early measurement of serum lipoprotein (a) [Lp(a)] levels in Chinese patients with type 2 diabetes (T2D) and acute ischemic stroke (AIS). The study population comprised 232 consecutive patients with an AIS diagnosis complicated with T2D. Functional outcome was obtained on month 3 according to the modified Rankin Scale (mRS). Unfavorable functional outcome was defined as a mRS score of 3 to 6 points. The prognostic value of Lp(a) at admission to predict the unfavorable functional outcome 3 months after stroke onset was compared with the National Institutes of Health Stroke Scale score and other known outcome predictors...
December 20, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29260495/caffeic-acid-phenethyl-ester-cape-protects-pc12-cells-from-cisplatin-induced-neurotoxicity-by-activating-the-ngf-signaling-pathway
#14
Rafaela Scalco Ferreira, Neife Aparecida Guinaim Dos Santos, Nádia Maria Martins, Laís Silva Fernandes, Antonio Cardozo Dos Santos
Cisplatin is a highly effective chemotherapeutic drug that is toxic to the peripheral nervous system. Findings suggest that axons are early targets of the neurotoxicity of cisplatin. Although many compounds have been reported as neuroprotective, there is no effective treatment against the neurotoxicity of cisplatin. Caffeic acid phenethyl ester (CAPE) is a propolis component with neuroprotective potential mainly attributed to antioxidant and anti-inflammatory mechanisms. We have recently demonstrated the neurotrophic potential of CAPE in a cellular model of neurotoxicity related to Parkinson's disease...
December 19, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29260494/developmental-exposure-to-low-levels-of-ethinylestradiol-affects-play-behavior-in-juvenile-female-rats
#15
Marco Zaccaroni, Alessandro Massolo, Daniele Della Seta, Francesca Farabollini, Giulietta Giannelli, Leonida Fusani, Francesco Dessì-Fulgheri
Juvenile social play contributes to the development of adult social and emotional skills in humans and non-human animals, and is therefore a useful endpoint to study the effects of endocrine disrupters on behavior in animal models. Ethinylestradiol (EE2) is a widely produced, powerful synthetic estrogen that is widespread in the environment mainly because is a component of the contraceptive pill. In addition, fetuses may be exposed to EE2 when pregnancy is undetected during contraceptive treatment. To understand whether exposure to EE2 during gestation or lactation affects social play, we exposed 72 female Sprague-Dawley rats to EE2 or vehicle either during gestation (gestation day (GD) 5 through GD 20) or during lactation (from postnatal day (PND) 1 through PND 21)...
December 19, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29243196/chronic-mild-hyperhomocysteinemia-alters-inflammatory-and-oxidative-nitrative-status-and-causes-protein-dna-damage-as-well-as-ultrastructural-changes-in-cerebral-cortex-is-acetylsalicylic-acid-neuroprotective
#16
Daniella de S Moreira, Paula W Figueiró, Cassiana Siebert, Caroline A Prezzi, Francieli Rohden, Fatima C R Guma, Vanusa Manfredini, Angela T S Wyse
Homocysteine is a sulfur-containing amino acid derived from methionine metabolism. When plasma homocysteine levels exceed 10-15 μM, there is a condition known as hyperhomocysteinemia, which occur as a result of an inborn error of methionine metabolism or by non-genetic causes. Mild hyperhomocysteinemia is considered a risk factor for development of neurodegenerative diseases. The objective of the present study was to evaluate whether acetylsalicylic acid has neuroprotective role on the effect of homocysteine on inflammatory, oxidative/nitrative stress, and morphological parameters in cerebral cortex of rats subjected to chronic mild hyperhomocysteinemia...
December 14, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29235064/induction-of-neuroinflammatory-response-and-histopathological-alterations-caused-by-quinolinic-acid-administration-in-the-striatum-of-glutaryl-coa-dehydrogenase-deficient-mice
#17
Alexandre Umpierrez Amaral, Bianca Seminotti, Janaína Camacho da Silva, Francine Hehn de Oliveira, Rafael Teixeira Ribeiro, Carmen Regla Vargas, Guilhian Leipnitz, Abel Santamaría, Diogo Onofre Souza, Moacir Wajner
Glutaric acidemia type I (GA I) is an inherited neurometabolic disorder caused by a severe deficiency of the mitochondrial glutaryl-CoA dehydrogenase (GCDH) activity. Patients usually present progressive cortical leukodystrophy and commonly develop acute bilateral striatal degeneration mainly during infections that markedly worse their prognosis. A role for quinolinic acid (QA), a key metabolite of the kynurenine pathway, which is activated during inflammatory processes, on the pathogenesis of the acute striatum degeneration occurring in GA I was proposed but so far has not yet been evaluated...
December 12, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29230633/alteration-of-the-pac1-receptor-expression-in-the-basal-ganglia-of-mptp-induced-parkinsonian-macaque-monkeys
#18
M Feher, B Gaszner, A Tamas, A L Gil-Martinez, E Fernandez-Villalba, M T Herrero, D Reglodi
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a well-known neuropeptide with strong neurotrophic and neuroprotective effects. PACAP exerts its protective actions via three G protein-coupled receptors: the specific Pac1 receptor (Pac1R) and the Vpac1/Vpac2 receptors, the neuroprotective effects being mainly mediated by the Pac1R. The protective role of PACAP in models of Parkinson's disease and other neurodegenerative diseases is now well-established in both in vitro and in vivo studies. PACAP and its receptors occur in the mammalian brain, including regions associated with Parkinson's disease...
December 11, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29218504/temporal-spatial-profiling-of-pedunculopontine-galanin-cholinergic-neurons-in-the-lactacystin-rat-model-of-parkinson-s-disease
#19
Joanna L Elson, Rafael Kochaj, Richard Reynolds, Ilse S Pienaar
Parkinson's disease (PD) is conventionally seen as resulting from single-system neurodegeneration affecting nigrostriatal dopaminergic neurons. However, accumulating evidence indicates multi-system degeneration and neurotransmitter deficiencies, including cholinergic neurons which degenerate in a brainstem nucleus, the pedunculopontine nucleus (PPN), resulting in motor and cognitive impairments. The neuropeptide galanin can inhibit cholinergic transmission, while being upregulated in degenerating brain regions associated with cognitive decline...
December 7, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29218503/differential-alterations-in-metabolism-and-proteolysis-related-proteins-in-human-parkinson-s-disease-substantia-nigra
#20
Edna Grünblatt, Josefine Ruder, Camelia Maria Monoranu, Peter Riederer, Moussa Bh Youdim, Silvia A Mandel
Parkinson's disease is the most common neurodegenerative disorder after Alzheimer's disease, with the majority of cases being sporadic or "idiopathic". The aetiology of the sporadic form is still unknown, but there is a broad consensus that Parkinson's disease involves multiple pathways. In previous human post-mortem studies investigating substantia nigra of parkinsonian subjects, gene expression alterations in various metabolic pathways including protein folding, trafficking, aggregation, ubiquitination and oxidative stress were found...
December 7, 2017: Neurotoxicity Research
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