Experimentally-induced maternal hypothyroidism alters enzyme activities and the sensorimotor cortex of the offspring rats.

In this study, we used an experimental model of congenital hypothyroidism to show that deficient thyroid hormones (TH) disrupt different neurochemical, morphological and functional aspects in the cerebral cortex of 15-day-old offspring. Our results showing decreased glutamine synthetase (GS) activity and Ca overload in the cerebral cortex of hypothyroid pups suggest misregulated glutamate metabolism associated with developmentally induced TH deficiency. The C-MeAIB accumulation indicates upregulated System A activity and glutamine uptake by neurons.

Methylphenidate disrupts cytoskeletal homeostasis and reduces membrane-associated lipid content in juvenile rat hippocampus.

Although methylphenidate (MPH) is ubiquitously prescribed to children and adolescents, the consequences of chronic utilization of this psychostimulant are poorly understood. In this study, we investigated the effects of MPH on cytoskeletal homeostasis and lipid content in rat hippocampus. Wistar rats received intraperitoneal injections of MPH (2.

Delayed neurochemical effects of prenatal exposure to MeHg in the cerebellum of developing rats.

Human fetuses and neonates are particularly vulnerable to methylmercury (MeHg)-induced brain damage and are sensitive even to low exposure levels. Previous work of our group evidence that prenatal exposure to MeHg causes cognitive and behavioral alterations and disrupt hippocampus signaling. The current study aimed to investigate the effect of gestational exposure of rats to MeHg at low doses (1 or 2 mg/kg) on parameters of redox imbalance and key signaling pathways in the cerebellum of their offspring.

Reverse T interacts with αvβ3 integrin receptor and restores enzyme activities in the hippocampus of hypothyroid developing rats: Insight on signaling mechanisms.

In the present study we provide evidence that 3,3',5'-triiodothyronine (reverse T, rT) restores neurochemical parameters induced by congenital hypothyroidism in rat hippocampus. Congenital hypothyroidism was induced by adding 0.05% propylthiouracil in the drinking water from gestation day 8 and continually up to lactation day 15.

Kynurenic Acid Prevents Cytoskeletal Disorganization Induced by Quinolinic Acid in Mixed Cultures of Rat Striatum.

Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan known to modulate a number of mechanisms involved in neural dysfunction. Although its activity in the brain has been widely studied, the effect of KYNA counteracting the actions of quinolinic acid (QUIN) remains unknown. The present study aims at describing the ability of 100 μM KYNA preventing cytoskeletal disruption provoked by QUIN in astrocyte/neuron/microglia mixed culture.

Developmental neurotoxicity of the hippocampus following in utero exposure to methylmercury: impairment in cell signaling.

In this study, we assessed some hippocampal signaling cascades and behavioral impairments in 30-day-old rat pups prenatally exposed to methylmercury (MeHg). Pregnant rats were exposed to 1.0 or 2.

Vitamin D Reverses the Hippocampal Cytoskeleton Imbalance But Not Memory Deficits Caused by Ovariectomy in Adult Wistar Rats.

The objective of study was to investigate changes caused by ovariectomy (OVX) on aversive and non-aversive memories, as well as on cytoskeleton phosphorylating system and on vitamin D receptor (VDR) immunocontent in hippocampus. The neuroprotective role of vitamin D was also investigated. Ninety-day-old female Wistar rats were divided into four groups: SHAM, OVX, VITAMIN D and OVX + VITAMIN D; 30 days after the OVX, vitamin D supplementation (500 IU/kg), by gavage, for 30 days was started.

Cytoskeleton as a Target of Quinolinic Acid Neurotoxicity: Insight from Animal Models.

Cytoskeletal proteins are increasingly recognized as having important roles as a target of the action of different neurotoxins. In the last years, several works of our group have shown that quinolinic acid (QUIN) was able to disrupt the homeostasis of the cytoskeleton of neural cells and this was associated with cell dysfunction and neurodegeneration. QUIN is an excitotoxic metabolite of tryptophan metabolism and its accumulation is associated with several neurodegenerative diseases.

Astrocyte-neuron interaction in diphenyl ditelluride toxicity directed to the cytoskeleton.

Diphenylditelluride (PhTe) is a neurotoxin that disrupts cytoskeletal homeostasis. We are showing that different concentrations of (PhTe) caused hypophosphorylation of glial fibrillary acidic protein (GFAP), vimentin and neurofilament subunits (NFL, NFM and NFH) and altered actin organization in co-cultured astrocytes and neurons from cerebral cortex of rats. These mechanisms were mediated by N-methyl-d-aspartate (NMDA) receptors without participation of either L-type voltage-dependent calcium channels (L-VDCC) or metabotropic glutamate receptors.

Quinolinic acid neurotoxicity: Differential roles of astrocytes and microglia via FGF-2-mediated signaling in redox-linked cytoskeletal changes.

QUIN is a glutamate agonist playing a role in the misregulation of the cytoskeleton, which is associated with neurodegeneration in rats. In this study, we focused on microglial activation, FGF2/Erk signaling, gap junctions (GJs), inflammatory parameters and redox imbalance acting on cytoskeletal dynamics of the in QUIN-treated neural cells of rat striatum. FGF-2/Erk signaling was not altered in QUIN-treated primary astrocytes or neurons, however cytoskeleton was disrupted.

Neurotoxicity of Methylmercury in Isolated Astrocytes and Neurons: the Cytoskeleton as a Main Target.

In the present work, we focused on mechanisms of methylmercury (MeHg) toxicity in primary astrocytes and neurons of rats. Cortical astrocytes and neurons exposed to 0.5-5 μM MeHg present a link among morphological alterations, glutathione (GSH) depletion, glutamate dyshomeostasis, and cell death.

Calcium signaling mechanisms disrupt the cytoskeleton of primary astrocytes and neurons exposed to diphenylditelluride.

Background: Diphenylditelluride (PhTe)2 is a potent neurotoxin disrupting the homeostasis of the cytoskeleton.

Methods: Cultured astrocytes and neurons were incubated with (PhTe)2, receptor antagonists and enzyme inhibitors followed by measurement of the incorporation of [32P]orthophosphate into intermediate filaments (IFs).

Results: (PhTe)2 caused hyperphosphorylation of glial fibrillary acidic protein (GFAP), vimentin and neurofilament subunits (NFL, NFM and NFH) from primary astrocytes and neurons, respectively.

Acute Hyperammonemia Induces NMDA-Mediated Hypophosphorylation of Intermediate Filaments Through PP1 and PP2B in Cerebral Cortex of Young Rats.

In the present work, we studied the effects of toxic ammonia levels on the cytoskeleton of neural cells, with emphasis in the homeostasis of the phosphorylating system associated with the intermediate filaments (IFs). We used in vivo and in vitro models of acute hyperammonemia in 10- and 21-day-old rats. In the in vivo model, animals were intraperitoneally injected with ammonium acetate (7 mmol/Kg), and the phosphorylation level of the cytoskeletal proteins was analyzed in the cerebral cortex and hippocampus 30 and 60 min after injection.

High postnatal susceptibility of hippocampal cytoskeleton in response to ethanol exposure during pregnancy and lactation.

Ethanol exposure to offspring during pregnancy and lactation leads to developmental disorders, including central nervous system dysfunction. In the present work, we have studied the effect of chronic ethanol exposure during pregnancy and lactation on the phosphorylating system associated with the astrocytic and neuronal intermediate filament (IF) proteins: glial fibrillary acidic protein (GFAP), and neurofilament (NF) subunits of low, medium, and high molecular weight (NFL, NFM, and NFH, respectively) in 9- and 21-day-old pups. Female rats were fed with 20% ethanol in their drinking water during pregnancy and lactation.

NMDA Receptors and Oxidative Stress Induced by the Major Metabolites Accumulating in HMG Lyase Deficiency Mediate Hypophosphorylation of Cytoskeletal Proteins in Brain From Adolescent Rats: Potential Mechanisms Contributing to the Neuropathology of This Disease.

Neurological symptoms and cerebral abnormalities are commonly observed in patients with 3-hydroxy-3-methylglutaryl-CoA lyase (HMG lyase) deficiency, which is biochemically characterized by predominant tissue accumulation of 3-hydroxy-3-methylglutaric (HMG), 3-methylglutaric (MGA), and 3-methylglutaconic (MGT) acids. Since the pathogenesis of this disease is poorly known, the present study evaluated the effects of these compounds on the cytoskeleton phosphorylating system in rat brain. HMG, MGA, and MGT caused hypophosphorylation of glial fibrillary acidic protein (GFAP) and of the neurofilament subunits NFL, NFM, and NFH.

Crosstalk Among Disrupted Glutamatergic and Cholinergic Homeostasis and Inflammatory Response in Mechanisms Elicited by Proline in Astrocytes.

Hyperprolinemias are inherited disorder of proline (Pro) metabolism. Patients affected may present neurological manifestations, but the mechanisms of neural excitotoxicity elicited by hyperprolinemia are far from being understood. Considering that the astrocytes are important players in neurological disorders, the aim of the present work was to study the effects 1 mM Pro on glutamatergic and inflammatory parameters in cultured astrocytes from cerebral cortex of rats, exploring some molecular mechanisms underlying the disrupted homeostasis of astrocytes exposed to this toxic Pro concentration.

Quinolinic acid induces disrupts cytoskeletal homeostasis in striatal neurons. Protective role of astrocyte-neuron interaction.

Quinolinic acid (QUIN) is an endogenous metabolite of the kynurenine pathway involved in several neurological disorders. Among the several mechanisms involved in QUIN-mediated toxicity, disruption of the cytoskeleton has been demonstrated in striatally injected rats and in striatal slices. The present work searched for the actions of QUIN in primary striatal neurons.

Signaling mechanisms and disrupted cytoskeleton in the diphenyl ditelluride neurotoxicity.

Evidence from our group supports that diphenyl ditelluride (PhTe)2 neurotoxicity depends on modulation of signaling pathways initiated at the plasma membrane. The (PhTe)2-evoked signal is transduced downstream of voltage-dependent Ca(2+) channels (VDCC), N-methyl-D-aspartate receptors (NMDA), or metabotropic glutamate receptors activation via different kinase pathways (protein kinase A, phospholipase C/protein kinase C, mitogen-activated protein kinases (MAPKs), and Akt signaling pathway). Among the most relevant cues of misregulated signaling mechanisms evoked by (PhTe)2 is the cytoskeleton of neural cells.

Acute intrastriatal injection of quinolinic acid provokes long-lasting misregulation of the cytoskeleton in the striatum, cerebral cortex and hippocampus of young rats.

Quinolinic acid (QUIN) is a neuroactive metabolite of the kinurenine pathway, considered to be involved in aging and some neurodegenerative disorders, including Huntington׳s disease. In the present work we have studied the long-lasting effect of acute intrastriatal injection of QUIN (150 nmol/0.5 µL) in 30 day-old rats on the phosphorylating system associated with the astrocytic and neuronal intermediate filament (IF) proteins: glial fibrillary acidic protein (GFAP), and neurofilament (NF) subunits (NFL, NFM and NFH) respectively, until 21 days after injection.

Biochemical, histopathological and behavioral alterations caused by intrastriatal administration of quinolic acid to young rats.

Quinolinic acid (QUIN) is a neuroactive metabolite of the kinurenine pathway, and is considered to be involved in aging and some neurodegenerative disorders, including Huntington's disease. QUIN was injected intrastriatally into adolescent rats, and biochemical and histopathological analyses in the striatum, cortex, and hippocampus, as well as behavioral tests, were carried out in the rats over a period of 21 days after drug injection. Decreased [(3)H]glutamate uptake and increased (45)Ca(2+) uptake were detected shortly after injection in the striatum and cerebral cortex.

The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid.

Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions.

Roundup disrupts male reproductive functions by triggering calcium-mediated cell death in rat testis and Sertoli cells.

Glyphosate is the primary active constituent of the commercial pesticide Roundup. The present results show that acute Roundup exposure at low doses (36 ppm, 0.036 g/L) for 30 min induces oxidative stress and activates multiple stress-response pathways leading to Sertoli cell death in prepubertal rat testis.

Congenital hypothyroidism alters the oxidative status, enzyme activities and morphological parameters in the hippocampus of developing rats.

Congenital hypothyroidism is associated with delay in cell migration and proliferation in brain tissue, impairment of synapse formation, misregulation of neurotransmitters, hypomyelination and mental retardation. However, the mechanisms underlying the neuropsychological deficits observed in congenital hypothyroidism are not completely understood. In the present study we proposed a mechanism by which hypothyroidism leads to hippocampal neurotoxicity.

Methylglyoxal-induced cytotoxicity in neonatal rat brain: a role for oxidative stress and MAP kinases.

Carbonyl compounds such as methylglyoxal (MGO) seem to play an important role in complications resulting from diabetes mellitus, in aging and neurodegenerative disorders. In this study, we are showing, that MGO is able to suppress cell viability and induce apoptosis in the cerebral cortex and hippocampus of neonatal rats ex-vivo. These effects are partially related with ROS production, evaluated by DCFH-DA assay.