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Dive into the research topics where Teresa Montiel is active.

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Featured researches published by Teresa Montiel.


Neuroscience | 2003

Acetoacetate protects hippocampal neurons against glutamate-mediated neuronal damage during glycolysis inhibition.

Lourdes Massieu; M.L. Haces; Teresa Montiel; Karla Hernández-Fonseca

Glucose is the main substrate that fulfills energy brain demands. However, in some circumstances, such as diabetes, starvation, during the suckling period and the ketogenic diet, brain uses the ketone bodies, acetoacetate and beta-hydroxybutyrate, as energy sources. Ketone body utilization in brain depends directly on its blood concentration, which is normally very low, but increases substantially during the conditions mentioned above. Glutamate neurotoxicity has been implicated in neurodegeneration associated with brain ischemia, hypoglycemia and cerebral trauma, conditions related to energy failure, and to elevation of glutamate extracellular levels in brain. In recent years substantial evidence favoring a close relation between glutamate neurotoxic potentiality and cellular energy levels, has been compiled. We have previously demonstrated that accumulation of extracellular glutamate after inhibition of its transporters, induces neuronal death in vivo during energy impairment induced by glycolysis inhibition. In the present study we have assessed the protective potentiality of the ketone body, acetoacetate, against glutamate-mediated neuronal damage in the hippocampus of rats chronically treated with the glycolysis inhibitor, iodoacetate, and in hippocampal cultured neurons exposed to a toxic concentration of iodoacetate. Results show that acetoacetate efficiently protects against glutamate neurotoxicity both in vivo and in vitro probably by a mechanism involving its role as an energy substrate.


Experimental Neurology | 2002

β-Amyloid neurotoxicity is exacerbated during glycolysis inhibition and mitochondrial impairment in the rat hippocampus in vivo and in isolated nerve terminals: Implications for alzheimer's disease

Clorinda Arias; Teresa Montiel; Ricardo Quiroz-Baez; Lourdes Massieu

Abstract Senile plaques composed mainly by β-amyloid (Aβ) protein are one of the pathological hallmarks of Alzheimers disease (AD). In vitro, Aβ and its active fragment 25–35 have been shown either to be directly neurotoxic or to exacerbate the damaging effect of other neurotoxic insults. However, the attempts to replicate Aβ neurotoxicity in vivo have yielded conflicting results. One of the most consistent alterations in AD is a reduced resting glucose utilization. Important evidence suggests that impairment of brain energy metabolism can lead to neuronal damage or facilitate the deleterious effects of some neurotoxic agents. In the present study we have investigated the influence of glycolysis inhibition induced by iodoacetate, and mitochondrial impairment induced by 3-nitropropionic acid (3-NP), in the toxicity of Aβ. We have studied Aβ neurotoxicity during energy deficiency both in vivo in the dentate gyrus of the hippocampal formation and in presynaptic terminals isolated from neocortex and hippocampus. Results show that during metabolic inhibition an enhanced vulnerability of hippocampal neurons to Aβ peptide toxicity occurs, probably resulting from decreased glucose metabolism and mitochondrial ATP production. Synaptosomal response to energy impairment and Aβ toxicity was evaluated by the MTT assay. Results suggest that synapses may be particularly sensitive to metabolic perturbation, which in turn exacerbates Aβ toxicity. The present data provide experimental support to the hypothesis that certain risk factors such as metabolic dysfunction and amyloid accumulation may interact to exacerbate AD, and that metabolic substrates such as pyruvate may play a role as a therapeutic tool.


Neurobiology of Disease | 2009

Glutamate toxicity in the striatum of the R6/2 Huntington's disease transgenic mice is age-dependent and correlates with decreased levels of glutamate transporters

Ana María Estrada-Sánchez; Teresa Montiel; José Segovia; Lourdes Massieu

Glutamate excitotoxicity has been implicated in the neuropathology of Huntingtons disease (HD), due to the toxicity of glutamate receptor agonists on striatal medium spiny neurons (MSN), the most affected neuronal population in HD. Previous studies showed functional alterations of NMDA glutamate receptors and decreased expression of glutamate transporters in transgenic models and HD patients, suggesting the presence of excitotoxic damage. We have studied the vulnerability of the striatum to glutamate toxicity in R6/2 mice at 10 and 14 weeks of age. At 10 weeks R6/2 and wild-type mice are equally vulnerable to glutamate toxicity, while at 14 weeks transgenic mice show increased damage, as assessed by Nissl and Fluoro Jade staining. In addition, increased electrical brain activity is observed after glutamate administration in transgenic mice, as monitored electroencephalographically. According to western blot analysis, increased vulnerability to glutamate toxicity correlates with decreased levels of GLT-1 and GLAST glutamate transporters in the striatum.


Neuroscience | 2005

Differential effects of the substrate inhibitor l-trans-pyrrolidine-2,4-dicarboxylate (PDC) and the non-substrate inhibitor dl-threo-β-benzyloxyaspartate (dl-TBOA) of glutamate transporters on neuronal damage and extracellular amino acid levels in rat brain in vivo

Teresa Montiel; A. Camacho; Ana María Estrada-Sánchez; Lourdes Massieu

The extracellular concentration of glutamate is highly regulated by transporter proteins, due to its neurotoxic properties. Dysfunction or reverse activation of these transporters is related to the extracellular accumulation of excitatory amino acids and neuronal damage associated with ischemia and hypoglycemia. We have investigated by microdialysis the effects of the substrate and the non-substrate inhibitors of glutamate transporters, l-trans-2,4-pyrrolidine dicarboxylate (PDC) and DL-threo-beta-benzyloxyaspartate (DL-TBOA), respectively, on the extracellular levels of amino acids in the rat hippocampus in vivo. In addition, we have studied the effect of both inhibitors on neuronal damage after direct administration into the hippocampus and striatum. Electroencephalographic activity was recorded after the intrahippocampal infusion of DL-TBOA or PDC. Microdialysis administration of 500 microM DL-TBOA into the hippocampus increased 3.4- and nine-fold the extracellular levels of aspartate and glutamate, respectively. Upon stereotaxic administration it induced neuronal damage dose-dependently in CA1 and dentate gyrus, and convulsive behavior. Electroencephalographic recording showed the appearance of limbic seizures in the hippocampus after DL-TBOA infusion. In the striatum it also induced dose-dependent neuronal damage. These effects were prevented by the i.p. administration of the glutamate receptor antagonists (+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-iminemaleate and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline. In contrast to dl-TBOA, PDC (500 microM) induced a more discrete elevation of excitatory amino acids levels (2.6- and three-fold in aspartate and glutamate, respectively), no neuronal damage or behavioral changes, and no alterations in electroencephalographic activity. The differential results obtained with DL-TBOA and PDC might be attributed to their distinct effects on the extracellular concentration of amino acids. Results are relevant to the understanding of the role of glutamate transporters in amino acid removal or release and the induction of excitotoxic cell death.


Experimental Neurology | 2006

Role of oxidative stress on β-amyloid neurotoxicity elicited during impairment of energy metabolism in the hippocampus : Protection by antioxidants

Teresa Montiel; Ricardo Quiroz-Baez; Lourdes Massieu; Clorinda Arias

Age-associated oxidative stress has been implicated in neuronal damage linked with Alzheimers disease (AD). In addition to the role of beta-amyloid peptide (Abeta) in the pathogenesis of AD, reduced glucose oxidative metabolism and decreased mitochondrial activity have been suggested as associated factors. However, the relationship between Abeta toxicity, metabolic impairment, and oxidative stress is far from being understood. In vivo neurotoxicity of Abeta25-35 peptide has been conflicting. However, in previous studies, we have shown that Abeta25-35 consistently induces synaptic toxicity and neuronal death in the hippocampus in vivo, when administered during moderate glycolytic or mitochondrial inhibition. In the present study, we have investigated whether enhancement of Abeta neurotoxicity during these conditions involves oxidative stress. Results show increased lipoperoxidation (LPO) when Abeta is administered in the hippocampus of rats previously treated with the glycolysis inhibitor, iodoacetate. Neuronal damage and LPO are efficiently prevented by vitamin E, while the spin trapper, alpha-phenyl-N-tert-butyl nitrone, shows partial protection. Abeta stimulates LPO in synaptosomes, but toxicity is only observed in the presence of metabolic inhibitors. Damage and LPO are efficiently prevented by vitamin E. The present results suggest an interaction between oxidative stress and metabolic impairment in the Abeta neurotoxic cascade.


Neuroscience | 2001

Neurotoxicity of glutamate uptake inhibition in vivo: correlation with succinate dehydrogenase activity and prevention by energy substrates

Lourdes Massieu; P. Del Río; Teresa Montiel

Impairment of glutamate uptake or the reverse action of its transporters has been suggested as the mechanism responsible for the increased glutamate extracellular levels associated with ischemic neuronal damage. In previous studies we have shown that glutamate uptake inhibition by L-trans-pyrrolidine-2,4-dicarboxylate (PDC) in the rat striatum and hippocampus in vivo does not induce neuronal death despite the notable increase in the extracellular levels of glutamate and aspartate. However, PDC intracerebral administration leads to neuronal death in rats chronically injected with the mitochondrial toxin 3-nitropropionic acid (3-NP), an inhibitor of succinate dehydrogenase (SDH). In the present study we have determined the time course of inhibition of SDH activity in the striatum of rats acutely injected with a single dose of 3-NP (20 mg/kg), and studied its relation to PDC neurotoxicity. PDC induced larger lesions when administered during maximum inhibition of SDH activity while smaller lesions were found when it was injected during recovery of enzyme activity. We also studied the neuroprotective effect of different energy substrates such as creatine, pyruvate, and the ketone bodies beta-hydroxybutyrate and acetoacetate in this experimental model. Our results show partial protection with all compounds except for beta-hydroxybutyrate that showed no protection, while MK-801 completely prevented PDC-induced neuronal damage. We believe that the present results might be of relevance for the understanding of the mechanisms responsible for ischemic neuronal death and its prevention.


Neuroscience | 2010

Selective vulnerability of brain regions to oxidative stress in a non-coma model of insulin-induced hypoglycemia

M.L. Haces; Teresa Montiel; Lourdes Massieu

Insulin-induced hypoglycemia causes the death of neurons in particular brain regions including the cerebral cortex, the striatum and the hippocampus, while the cerebellum and the brain stem are more resistant. The mechanisms underlying this selective vulnerability to hypoglycemic damage are unknown. In the present study we have analyzed the presence of lipoperoxidation products and nitrosilated protein residues in different rat brain regions during and after the induction of hypoglycemia. Insulin-injected hypoglycemic rats were sacrificed before the onset of the isoelectric period or infused with glucose to end hypoglycemia, and then sacrificed at different times. Increased lipoperoxidation levels were observed before the onset of the isoelectric period, while 3-nitrotyrosine (NT) residues in proteins and NT-positive cells were only observed after glucose reperfusion. These changes were found only in vulnerable brain regions, while none of them was evident in the cerebellum, suggesting a correlation between oxidative damage and vulnerability to hypoglycemic neuronal death in selective brain regions. Results suggest that a pro-oxidant state is promoted in certain brain regions during hypoglycemia and after the glucose reperfusion phase, which might result from the activation of several oxidative stress pathways and may be related to subsequent cell death.


Neurochemical Research | 2006

d-β-Hydroxybutyrate Prevents Glutamate-Mediated Lipoperoxidation and Neuronal Damage Elicited during Glycolysis Inhibition In Vivo

Jana Mejía-Toiber; Teresa Montiel; Lourdes Massieu

Excitotoxic neuronal death mediated by over-activation of glutamate receptors has been implicated in ischemia, hypoglycemia and some neurodegenerative diseases. It involves oxidative stress and is highly facilitated during impairment of energy metabolism. We have shown previously that in vivo systemic glycolysis inhibition with iodoacetate (IOA), exacerbates glutamate excitotoxicity. We have now investigated whether this effect involves oxidative damage to membrane lipids, as evaluated by the presence of thiobarbituric acid-reactive substances. We have also tested whether the ketone body, d-β-hydroxybutyrate (d-BHB), prevents lipoperoxidation and tissue damage. Results show that glutamate intrastriatal injection in control rats transiently enhances lipoperoxidation, while in IOA-treated animals increased lipoperoxidation is sustained. Treatment with d-BHB significantly reduces striatal lesions and lipoperoxidation. Vitamin E also reduced neuronal damage and lipoperoxidation. Results suggest that glycolysis impairment favors a pro-oxidant condition and situates oxidative damage as an important mediator of in vivo induced excitotoxicity. Results provide evidence for the neuroprotective effect of d-BHB against glutamate toxicity.


Neurochemistry International | 2013

Neuronal damage and cognitive impairment associated with hypoglycemia: An integrated view

Gabriela Languren; Teresa Montiel; Alberto Julio-Amilpas; Lourdes Massieu

The aim of the present review is to offer a current perspective about the consequences of hypoglycemia and its impact on the diabetic disorder due to the increasing incidence of diabetes around the world. The main consequence of insulin treatment in type 1 diabetic patients is the occurrence of repetitive periods of hypoglycemia and even episodes of severe hypoglycemia leading to coma. In the latter, selective neuronal death is observed in brain vulnerable regions both in humans and animal models, such as the cortex and the hippocampus. Cognitive damage subsequent to hypoglycemic coma has been associated with neuronal death in the hippocampus. The mechanisms implicated in selective damage are not completely understood but many factors have been identified including excitotoxicity, oxidative stress, zinc release, PARP-1 activation and mitochondrial dysfunction. Importantly, the diabetic condition aggravates neuronal damage and cognitive failure induced by hypoglycemia. In the absence of coma prolonged and severe hypoglycemia leads to increased oxidative stress and discrete neuronal death mainly in the cerebral cortex. The mechanisms responsible for cell damage in this condition are still unknown. Recurrent moderate hypoglycemia is far more common in diabetic patients than severe hypoglycemia and currently important efforts are being done in order to elucidate the relationship between cognitive deficits and recurrent hypoglycemia in diabetics. Human studies suggest impaired performance mainly in memory and attention tasks in healthy and diabetic individuals under the hypoglycemic condition. Only scarce neuronal death has been observed under moderate repetitive hypoglycemia but studies suggest that impaired hippocampal synaptic function might be one of the causes of cognitive failure. Recent studies have also implicated altered mitochondrial function and mitochondrial oxidative stress.


Journal of Neuropathology and Experimental Neurology | 2011

Activation of NOX2 by the Stimulation of Ionotropic and Metabotropic Glutamate Receptors Contributes to Glutamate Neurotoxicity In Vivo Through the Production of Reactive Oxygen Species and Calpain Activation

Alicia Guemez-Gamboa; Ana María Estrada-Sánchez; Teresa Montiel; Blanca Páramo; Lourdes Massieu; Julio Morán

Prolonged activation of glutamate receptors leads to excitotoxicity. Several processes such as reactive oxygen species (ROS) production and activation of the calcium-dependent protease, calpain, contribute to glutamate-induced damage. It has been suggested that the ROS-producing enzyme, NADPH oxidase (NOX), plays a role in excitotoxicity. Studies have reported NOX activation after NMDA receptor stimulation during excitotoxic damage, but the role of non-NMDA and metabotropic receptors is unknown. We evaluated the roles of different glutamate receptor subtypes on NOX activation and neuronal death induced by the intrastriatal administration of glutamate in mice. In wild-type mice, NOX2 immunoreactivity in neurons and microglia was stimulated by glutamate administration, and it progressively increased as microglia became activated; calpain activity was also induced. By contrast, mice lacking NOX2 were less vulnerable to excitotoxicity, and there was reduced ROS production and protein nitrosylation, microglial reactivity, and calpain activation. These results suggest that NOX2 is stimulated by glutamate in neurons and reactive microglia through the activation of ionotropic and metabotropic receptors. Neuronal damage involves ROS production by NOX2, which, in turn, contributes to calpain activation.

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Lourdes Massieu

National Autonomous University of Mexico

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Simón Brailowsky

National Autonomous University of Mexico

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Ana María Estrada-Sánchez

National Autonomous University of Mexico

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Eduardo Calixto

National Autonomous University of Mexico

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A. Camacho

National Autonomous University of Mexico

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Clorinda Arias

National Autonomous University of Mexico

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César Casasola

National Autonomous University of Mexico

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Cristian Gerónimo-Olvera

National Autonomous University of Mexico

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Ricardo Tapia

National Autonomous University of Mexico

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Alberto Julio-Amilpas

National Autonomous University of Mexico

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