Long-term and low-dose malathion exposure causes cognitive impairment in adult mice: evidence of hippocampal mitochondrial dysfunction, astrogliosis and apoptotic events.
Archives of Toxicology 90(3):647 (2016)
The organophosphorus (OP) pesticide malathion is a neurotoxic compound whose acute toxicity is primarily caused by the inhibition of acetylcholinesterase (AChE), leading to cholinergic syndrome-related symptoms. Some lines of evidence indicate that long-term exposure to low levels of OP may prod...
Attentional performance, impulsivity, and related neurotransmitter systems in apoE2, apoE3, and apoE4 female transgenic mice.
Psychopharmacology 233(2):295 (2016)
The apolipoprotein E (apoE) genotype influences cognitive performance in humans depending on age and sex. While the detrimental role of the apoE4 isoform on spatial learning and memory has been well-established in humans and rodents, less is known on its impact on the executive functions.
Toxicity evaluation of new agricultural fungicides in primary cultured cortical neurons.
Environmental Research 140:37 (2015)
Fungicides are crucial for food protection as well as for the production of crops of suitable quality and quantity to provide a viable economic return. Like other pesticides, fungicides are widely sprayed on agricultural land, especially in wine-growing areas, from where they can move-off after ...
Putative adverse outcome pathways relevant to neurotoxicity.
Critical Reviews in Toxicology 45(1):83 (2015)
The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological...
IrOx-carbon nanotube hybrids: a nanostructured material for electrodes with increased charge capacity in neural systems.
Acta Biomaterialia 10(10):4548 (2014)
Nanostructured iridium oxide-carbon nanotube hybrids (IrOx-CNT) deposited as thin films by dynamic electrochemical methods are suggested as novel materials for neural electrodes. Single-walled carbon nanotubes (SWCNT) serve as scaffolds for growing the oxide, yielding a tridimensional structure ...
Physical exercise improves synaptic dysfunction and recovers the loss of survival factors in 3xTg-AD mouse brain.
Neuropharmacology 81:55 (2014)
Physical exercise has become a potentially beneficial therapy for reducing neurodegeneration symptoms in Alzheimer's disease. Previous studies have shown that cognitive deterioration, anxiety and the startle response observed in 7-month-old 3xTg-AD mice were ameliorated after 6 months of free ac...
Influence of prenatal exposure to environmental pollutants on human cord blood levels of glutamate.
NeuroToxicology 40:102 (2014)
Some chemicals released into the environment, including mercury and some organochlorine compounds (OCs), are suspected to have a key role on subclinical brain dysfunction in childhood. Alteration of the glutamatergic system may be one mechanistic pathway. We aimed to determine whether mercury an...
Allopregnanolone and pregnanolone analogues modified in the C ring: synthesis and activity.
Journal of medicinal and pharmaceutical chemistry 56(6):2323 (2013)
(25R)-3β-Hydroxy-5α-spirostan-12-one (hecogenin) and 11α-hydroxypregn-4-ene-3,20-dione (11α-hydroxyprogesterone) were used as starting materials for the synthesis of a series of 11- and 12-substituted derivatives of 5ξ-pregnanolone (3α-hydroxy-5α-pregnan-20-one and 3α-hydroxy-5β-pregnan-20-one),...
Long term compulsivity on the 5-choice serial reaction time task after acute Chlorpyrifos exposure.
Toxicology Letters 216(2-3):73 (2013)
Pesticide exposure has been associated with neuropsychological and psychiatric impairments and neurodegenerative disorders. Pesticide exposure commonly causes a deficit in inhibitory control behaviours. In the present study, we investigated whether acute exposure to organophosphate (OP) chlorpyr...
Strategies and tools for preventing neurotoxicity: to test, to predict and how to do it.
NeuroToxicology 33(4):796 (2012)
A change in paradigm is needed in the prevention of toxic effects on the nervous system, moving from its present reliance solely on data from animal testing to a prediction model mostly based on in vitro toxicity testing and in silico modeling. According to the report published by the National R...
Allopregnanolone prevents dieldrin-induced NMDA receptor internalization and neurotoxicity by preserving GABA(A) receptor function.
Endocrinology 153(2):847 (2012)
Dieldrin is an endocrine disruptor that accumulates in mammalian adipose tissue and brain. It induces convulsions due to its antagonism of the γ-aminobutyric acid A receptor (GABA(A)R). We have previously reported that long-term exposure to dieldrin causes the internalization of the N-methyl-D-a...
Poor inhibitory control and neurochemical differences in high compulsive drinker rats selected by schedule-induced polydipsia.
Psychopharmacology 219(2):661 (2012)
Schedule-induced polydipsia (SIP), characterized by the development of excessive drinking under intermittent food reinforcement schedules, has been proposed as a model for obsessive-compulsive disorder, schizophrenia and drug abuse.
The purpose of this study is to investigate if individual diffe...
Differential estrogenic effects of the persistent organochlorine pesticides dieldrin, endosulfan, and lindane in primary neuronal cultures.
Toxicological Sciences 120(2):413 (2011)
The organochlorine chemicals endosulfan, dieldrin, and γ-hexachlorocyclohexane (lindane) are persistent pesticides to which people are exposed mainly via diet. Their antagonism of the γ-aminobutyric acid-A (GABA(A)) receptor makes them convulsants. They are also endocrine disruptors because of t...
Homeostatic regulation of glutamate neurotransmission in primary neuronal cultures.
Methods in Molecular Biology 758:253 (2011)
Glutamate is the mayor excitatory neurotransmitter in vertebrate nervous system. It has a crucial role in most brain functions under physiological conditions through the activation of both ionotropic and metabotropic glutamate receptors. In addition, extracellular glutamate concentration is tigh...
Defining and modeling known adverse outcome pathways: Domoic acid and neuronal signaling as a case study.
Environmental Toxicology and Chemistry 30(1):9 (2011)
An adverse outcome pathway (AOP) is a sequence of key events from a molecular-level initiating event and an ensuing cascade of steps to an adverse outcome with population-level significance. To implement a predictive strategy for ecotoxicology, the multiscale nature of an AOP requires computatio...
Gene-environment interactions: neurodegeneration in non-mammals and mammals.
NeuroToxicology 31(5):582 (2010)
The understanding of how environmental exposures interact with genetics in central nervous system dysfunction has gained great momentum in the last decade. Seminal findings have been uncovered in both mammalian and non-mammalian model in large result of the extraordinary conservation of both gen...
Impulsivity characterization in the Roman high- and low-avoidance rat strains: behavioral and neurochemical differences.
The selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats for rapid vs extremely poor acquisition of active avoidance behavior in a shuttle-box has generated two phenotypes with different emotional and motivational profiles. The phenotypic traits of the Roman rat lines/strains (ou...
Gender-Specific Neuroimmunoendocrine Response to Treadmill Exercise in 3xTg-AD Mice.
International Journal of Alzheimer's Disease 2010:128354 (2010)
The 3xTg-AD mouse develops a progressive Alzheimer's disease- (AD-) like brain pathology that causes cognitive- and neuropsychiatric-like symptoms of dementia. Since its neuroimmunoendocrine axis is likewise impaired, this mouse is also useful for modelling complex age-related neurodegeneration....
Methylmercury disrupts the balance between phosphorylated and non-phosphorylated cofilin in primary cultures of mice cerebellar granule cells. A proteomic study.
Toxicology and Applied Pharmacology 242(1):109 (2010)
Methylmercury is an environmental contaminant that is particularly toxic to the developing central nervous system; cerebellar granule neurons are especially vulnerable. Here, primary cultures of cerebellar granule cells (CGCs) were continuously exposed to methylmercury for up to 16 days in vitro...
GABAA receptor and cell membrane potential as functional endpoints in cultured neurons to evaluate chemicals for human acute toxicity.
Neurotoxicology and Teratology 32(1):52 (2010)
Toxicity risk assessment for chemical-induced human health hazards relies mainly on data obtained from animal experimentation, human studies and epidemiology. In vitro testing for acute toxicity based on cytotoxicity assays predicts 70-80% of rodent and human toxicity. The nervous system is part...