Papers by Consuelo Guerri
Los queratomas del casco, son procesos neoplasicos benignos, poco frecuentes, de origen epitelial... more Los queratomas del casco, son procesos neoplasicos benignos, poco frecuentes, de origen epitelial y que se desarrollan a partir de celulas productoras de queratina, localizadas en la pared del casco. Normalmente estos procesos estan relacionados con una historia previa de claudicacion intermitente. En este trabajo describimos las caracteristicas clinicas, macroscopicas e histopatologicas de un queratoma en el casco de un caballo con una historia clinica de cojera cronica. El animal presentaba una deformacion en la ranilla del casco debido a la presencia de una masa localizada en la union de la banda coronaria con la linea blanca. El estudio histopatologico mostro la presencia de una proliferacion neoplasica integrada por celulas epiteliales con formacion de multiples capas de queratina
Neural Regeneration Research, 2020
In recent years, a type of extracellular vesicles named exosomes has emerged that play an importa... more In recent years, a type of extracellular vesicles named exosomes has emerged that play an important role in intercellular communication under physiological and pathological conditions. These nanovesicles (30–150 nm) contain proteins, RNAs and lipids, and their internalization by bystander cells could alter their normal functions. This review focuses on recent knowledge about exosomes as messengers of neuron-glia communication and their participation in the physiological and pathological functions in the central nervous system. Special emphasis is placed on the role of exosomes under toxic or pathological stimuli within the brain, in which the glial exosomes containing inflammatory molecules are able to communicate with neurons and contribute to the pathogenesis of neuroinflammation and neurodegenerative disorders. Given the small size and characteristics of exosomes, they can cross the blood-brain barrier and be used as biomarkers and diagnosis for brain disorders and neuropathologies. Finally, although the application potential of exosome is still limited, current studies indicate that exosomes represent a promising strategy to gain pathogenic information to identify therapeutically targets and biomarkers for neurological disorders and neuroinflammation.
PLOS ONE, Apr 12, 2016
Ethanol induces brain damage and neurodegeneration by triggering inflammatory processes in glial ... more Ethanol induces brain damage and neurodegeneration by triggering inflammatory processes in glial cells through activation of Toll-like receptor 4 (TLR4) signaling. Recent evidence indicates the role of protein degradation pathways in neurodegeneration and alcoholic liver disease, but how these processes affect the brain remains elusive. We have demonstrated that chronic ethanol consumption impairs proteolytic pathways in mouse brain, and the immune response mediated by TLR4 receptors participates in these dysfunctions. We evaluate the in vitro effects of an acute ethanol dose on the autophagy-lysosome pathway (ALP) on WT and TLR4-/mouse astrocytes and neurons in primary culture, and how these changes affect cell survival. Our results show that ethanol induces overexpression of several autophagy markers (ATG12, LC3-II, CTSB), and increases the number of lysosomes in WT astrocytes, effects accompanied by a basification of lysosomal pH and by lowered phosphorylation levels of autophagy inhibitor mTOR, along with activation of complexes beclin-1 and ULK1. Notably, we found only minor changes between control and ethanol-treated TLR4-/mouse astroglial cells. Ethanol also triggers the expression of the inflammatory mediators iNOS and COX-2, but induces astroglial death only slightly. Blocking autophagy by using specific inhibitors increases both inflammation and cell death. Conversely, in neurons, ethanol down-regulates the autophagy pathway and triggers cell death, which is partially recovered by using autophagy enhancers. These results support the protective role of the ALP against ethanol-induced astroglial cell damage in a TLR4-dependent manner, and provide new insight into the mechanisms that underlie ethanol-induced brain damage and are neuronal sensitive to the ethanol effects.
European journal of biochemistry, May 1, 1977
The relative rate constant of protein degradation for a number of enzymes as well as for rat live... more The relative rate constant of protein degradation for a number of enzymes as well as for rat liver fractions and for 'soluble' and 'insoluble' protein of rat tissues has been measured by the double-isotope technique. This technique has been evaluated and found reliable for measurements involving half-lives of about 2-8 days and therefore generally useful for liver, kidney and possibly heart but not for brain and skeletal muscle. Carbamyl-phosphate synthase represents the major component (z 20 %) of the protein of rat liver mitoplasts. Particular attention was given to determine its turnover, for obviously this enzyme should be a good 'marker' for comparative studies with other mitochondrial proteins. The also hitherto unknown half-lives of malate dehydrogenase and of glutamate dehydrogenase from rat liver mitochondria have been measured.
CNS Neuroscience & Therapeutics, Jun 28, 2023
Neuroreport, Aug 1, 2001
In this paper we report that BDNF is able to stimulate the release of glutamate not only in cereb... more In this paper we report that BDNF is able to stimulate the release of glutamate not only in cerebrocortical nerve terminals, but also in cortical astrocytes. The process of glutamate release, in both nerve terminals and astrocytes, is dependent upon the extracellular and intracellular Ca 2 levels and involves exocytosis, since tetanus toxin treatment abolishes the release of glutamate from both preparations. Further, preincubation of nerve terminals or astrocytes with K252a (a tyrosine kinase inhibitor) inhibits BDNF-evoked glutamate release, suggesting the involvement of Trk B receptors in this process. In astrocytes, the level of BDNF-induced glutamate release is higher in immature than in more mature cells. The results suggest a new pathway of cross-talk between neurons and astrocytes, which may play a role in synaptic plasticity and neurotoxicity. NeuroReport 12:2673±2677 & 2001 Lippincott
Abstract Alcohol induces cell damage and can lead to neurodegeneration. Ethanol is capable of act... more Abstract Alcohol induces cell damage and can lead to neurodegeneration. Ethanol is capable of activating TLR4 receptors which, in turn, elicit a signaling cascade that leads to the generation of an inflammatory environment that is detrimental for cell survival. Autophagy has emerged as a protective cellular mechanism, triggered in the presence of toxic stimuli. However, its dysregulation is also involved in the pathogenesis of neurodegenerative and inflammatory diseases. By activating the TLR4 immune response, chronic ethanol consumption induces neuroinflammation and neuropathological changes, impairing the autophagic pathway by altering its main molecular switch, mTOR, which might contribute to neurodegeneration. Conversely, acute ethanol treatment is capable of eliciting a rapid autophagy response in glial cells, which is absent in neurons, to alleviate ethanol toxicity through mTOR inhibition and beclin-1 activation by innate immunity receptor TLR4. These findings could provide new insight into the mechanisms that underlie ethanol-induced brain damage.
Alcoholism: Clinical and Experimental Research, Apr 1, 1998
One of the most severe consequences of maternal ethanol consumption is the damage to the developi... more One of the most severe consequences of maternal ethanol consumption is the damage to the developing central nervous system, which is manifested by long-term cognitive and behavioral deficits in the offspring. Prenatal exposure to ethanol affects many crucial neurochemical and cellular components of the developing brain. Ethanol interferes with all of the stages of brain development, and the severity of the damage depends on the amount of ethanol intake and level of exposure. Experimental observations also indicate that the toxic effects of ethanol are not uniform: some brain regions are more affected than others and, even within a given region, some cell populations are more vulnerable than others. The neocortex, the hippocampus, and the cerebellum are the regions in which the neurotoxic effects of ethanol have been associated with the behavioral deficits. At the cellular level, ethanol disrupts basic developmental processes, including interference with division and proliferation, cell growth, and differentiation and the migration of maturing cells. Alterations in astroglia development and in neuronal-glial interactions may also influence the development of the nervous system. An impairment of several neurotransmitter systems and/or their receptors, as welt as changes in the endocrine environment during brain development, are also important factors involved in the behavioral dysfunctions observed after prenatal ethanol exposure. Finally, some molecular mechanisms of ethanol-induced behavioral dysfunctions will be discussed.
The International Journal of Developmental Biology, Jun 1, 2001
Prenatal alcohol exposure alters the liver and induces pathological changes in the morphology and... more Prenatal alcohol exposure alters the liver and induces pathological changes in the morphology and function of the Golgi apparatus (GA), including an accumulation or reduced transport of newly synthesized glycoconjugates which suggests that ethanol could affect the cytoskeleton (CSK) in hepatocytes. To test this possibility we have analysed, using various techniques, the effect of ethanol "in utero" on several CSK proteins including actin, αtubulin, cytokeratin, vimentin and the motor associated proteins dynein and kinesin. Our results show that this treatment increases the amount of both α-tubulin and cytokeratin and alters its distribution.
Alcohol and Alcoholism, Sep 1, 2015
Revista complutense de ciencias veterinarias, 2007
Advances in neurotoxicology, 2019
Abstract Alcohol is a neurotoxic compound whose abuse can cause alterations in brain structure an... more Abstract Alcohol is a neurotoxic compound whose abuse can cause alterations in brain structure and functions, although these effects are more dramatic while the brain develops. The molecular mechanisms of neurotoxic effects of alcohol are complex and remain largely unknown. Current evidence from human and animal studies supports the role of the neuroimmune system in many actions of ethanol on the central nervous system, including neurotoxicity. Different studies have shown that, by activating innate immune receptors TLRs (Toll-like receptors) and (NOD)-like receptors (inflammasome NLRs) in glial cells, alcohol triggers signaling pathways which culminate in the production of pro-inflammatory cytokines and chemokines that lead to neuroinflammation and brain damage, and contribute to alcohol-induced neuropathology and neurobehavioral dysfunctions. In this chapter we review the evidence which demonstrates that the activation of the innate immune system and TLRs participates in not only the neuropathology associated with alcohol abuse in adults and adolescents with binge drinking, but also in the effects of alcohol exposure during fetal development. The potential therapies that target neuroimmune pathways to treat neuropathological and behavioral consequences of alcohol abuse are also discussed.
PubMed, Feb 1, 2000
Endocytosis constitutes an essential process in the regulation of the expression of cell surface ... more Endocytosis constitutes an essential process in the regulation of the expression of cell surface molecules and receptors and, therefore, could participate in the neural-glial interactions occurring during brain development. However, the relationship between endocytic pathways in astroglial cells under physiological and pathological conditions remains poorly understood. We analyzed the endocytosis and transcytosis processes in growing astrocytes and the possible effect of ethanol on these processes. Evidence demonstrates that ethanol affects endocytosis in the liver and we showed that ethanol exposure during brain development alters astroglial development changing plasma membrane receptors and surface glycoprotein composition. To study these processes we use several markers for receptor-mediated endocytosis, fluid phase endocytosis and non-specific endocytosis. These markers were labeled for fluorescence microscopy and electron microscopy. 125I-BSA was used to study the effect of ethanol on the internalization and recycling of this macromolecule. The distribution of several proteins involved in endocytosis (caveolin, clathrin, rab5 and beta-COP) was analyzed using immunofluorescence, immunoelectron microscopy and immunoblotting. Our results indicate that growing astrocytes have a developed endocytic system mainly composed of caveolae, clathrin coated pits and vesicles, tubulo-vesicular and spheric endosomes, multivesicular bodies and lysosomes. Ethanol exposure induces a fragmentation of tubular endosomes, decreases the internalization of 125I-BSA, alters the processing of internalized BSA, and decreases the levels of caveolin, clathrin, rab5 and beta-COP. These results indicate that ethanol alters the endocytosis and transcytosis processes and impairs protein trafficking in astrocytes, which could perturb astrocyte surface expression of molecules involved in neuronal migration and maturation during brain development.
PubMed, Jun 1, 1992
This study has investigated the effect of prenatal alcohol exposure on the qualitative and quanti... more This study has investigated the effect of prenatal alcohol exposure on the qualitative and quantitative ultrastructure of proliferating and differentiated astrocytes in primary cultures as well as on the cytochemical activity of several subcellular phosphatase markers, including acid phosphatase, uridine diphosphatase, thiamine pyrophosphatase, 5'-nucleotidase and glucose-6-phosphatase. The astrocytes were obtained from 21-day-fetuses of both control and alcohol-fed rats. Our results show that several cell components, such as mitochondria, rough endoplasmic reticulum and lysosomes, exhibit qualitative and/or quantitative ultrastructural changes during the process of astrocyte maturation. In some cases these morphological changes are accompanied by variations in the cytochemical activity of enzymes located in these and other cell components, suggesting that these enzymes, and therefore the functional state of these organelles, are modulated during astrocyte development. When prenatally exposed to ethanol, both proliferating and differentiated astrocytes showed striking ultrastructural alterations compared with controls, including an increment of lysosomes as well as a decrease in the values of stereological parameters relative to mitochondria, rough endoplasmic reticulum and Golgi apparatus. Cytochemical analysis of these cells indicates that prenatal exposure to ethanol decreased the activities of all the enzymes tested, except for acid phosphatase, which was increased in both groups of treated astrocytes. These results suggest that prenatal exposure to ethanol could affect astrocytes during development in two different but probably complementary ways: a) by causing a delay in astrocyte maturation and, b) by inducing a direct toxic effect on these cells.
Neuropharmacology, 2021
Background: Substance use disorders and social stress are currently associated with changes in th... more Background: Substance use disorders and social stress are currently associated with changes in the immune system response by which they induce a proinflammatory state in neurons and glial cells that eventually modulates the reward system. Aims: The aim of the present work was to assess the role of the immune TLR4 (Toll-like receptors 4) and its signaling response in the increased contextual reinforcing effects of cocaine and reinforcing effects of ethanol (EtOH) induced by social defeat (SD) stress. Methods: Adult male C57BL/6 J wild-type (WT) mice and mice deficient in TLR4 (TLR4-KO) were assigned to experimental groups according to stress condition (exploration or SD). Three weeks after the last SD, conditioned place preference (CPP) was induced by a subthreshold cocaine dose (1 mg/kg), while another set underwent EtOH 6% operant self-administration (SA). Several inflammatory molecules were analyzed in the hippocampus and the striatum. Results: SD induced higher vulnerability to the conditioned rewarding effects of cocaine only in defeated WT mice. Similarly, defeated WT mice exhibited higher 6% EtOH consumption, an effect that was not observed in the defeated TLR4-KO group. However, the motivation to obtain the drug was observed in both genotypes of defeated animals. Notably, a significant upregulation of the protein proinflammatory markers NFkBp-p65, IL-1β, IL-17 A and COX-2 were observed only in the defeated WT mice, but not in their defeated TLR4-KO counterparts. Conclusions: These results suggest that TLR4 receptors mediate the neuroinflammatory response underlying the increase in the rewarding effects of cocaine and EtOH induced by social stress.
Journal of Psychopharmacology, Jun 18, 2019
Background: Alcohol exposure impairs brain development and leads to a range of behavioural and co... more Background: Alcohol exposure impairs brain development and leads to a range of behavioural and cognitive dysfunctions, termed as foetal alcohol spectrum disorders (FASD). Although different mechanisms have been proposed to participate in FASD, the molecular insights of such effects are still uncertain. Using a mouse model of FASD, we have previously shown that maternal binge-like alcohol drinking causes persistent effects on motor, cognitive and emotional-related behaviours associated with neuroimmune dysfunctions.
Pharmacogenetics and Genomics, Mar 1, 2009
Objectives It has been shown that acetaldehyde is an active metabolite of ethanol with central ac... more Objectives It has been shown that acetaldehyde is an active metabolite of ethanol with central actions that modulate behavior. Catalase has been proposed as the main enzyme responsible for the synthesis of acetaldehyde from ethanol in the brain. Recent studies, however, suggest that cytochrome, in particular the isoform P450 2E1, can also contribute to the central metabolism of ethanol. Methods Cytochrome P4502E1 knockout (KO) mice were used to assess the involvement of this isoenzyme in some of the acute and chronic behavioral effects of ethanol. Ethanol-induced locomotion, locomotor sensitization, and voluntary ethanol intake were evaluated in cytochrome P4502E1 KO mice and their wild-type (WT) counterparts. Results Spontaneous locomotion in KO mice was lower than that seen in the WT mice. Acute administration of ethanol (1.5 g/kg, intraperitoneally) increased locomotion to a similar extent in both strains of mice. Repeated intermittent administration of ethanol produced sensitization in both strains, but it was very subtle in the KO mice compared with the effect in the WT mice. KO mice showed a reduction in preference for ethanol intake at low concentrations (4-8% v/v). Interestingly, western blot for catalase in the brain and liver showed that KO mice had higher levels of catalase expression compared with WT mice. Conclusion These results show some impact of the mutation on ethanol-induced sensitization and on voluntary ethanol preference. The lack of a substantial impact of the mutation can be explained by the fact that the KO animals have a compensatory increase in catalase expression compared with WT mice, therefore possibly showing alterations in the formation of acetaldehyde after ethanol administration.
Experimental Cell Research, Oct 1, 2007
Astroglial cells are involved in the neuropathogenesis of several inflammatory diseases of the br... more Astroglial cells are involved in the neuropathogenesis of several inflammatory diseases of the brain, where the activation of inflammatory mediators and cytokines plays an important role. We have previously demonstrated that ethanol up-regulates inflammatory mediators in both brain and astroglial cells. Since Rho GTPases are involved in inflammatory responses of astrocytes where loss of stress fibers takes place and RhoE/Rnd3 disorganizes the actin cytoskeleton, the aim of the present study was to investigate the implication of this protein in the stimulation of inflammatory signaling induced by ethanol. Our findings show that RhoE expression induces a decrease in both RhoA and Rac. In addition, RhoE not only induces actin cytoskeleton disorganization but it also stimulates both the IRAK/ERK/NF-kappaB pathway and the COX-2 expression associated with the inflammatory response in these cells. Our results also show that ethanol exposure induces RhoE signaling in astrocytes. Preincubation of astrocytes with GF109203X, an inhibitor of PKCs, reduces the RhoE levels and abolishes the ethanol-induced activation of IRAK, NF-kappaB and the COX-2 expression. Furthermore, RhoE overexpression restores ethanol responses in astrocytes treated with the PKCs inhibitor. Altogether, our findings suggest that this small GTPase is involved in the stimulation of the inflammatory signaling induced by ethanol in astrocytes. These findings provide new insights into the molecular mechanism involved in the inflammatory responses in astrocytes.
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Papers by Consuelo Guerri