N-Acetylcysteine Attenuates Cisplatin Toxicity in the Cerebrum and Lung of Young Rats with Artificially Induced Protein Deficiency.

Neurotoxicity is a major obstacle in the effectiveness of Cisplatin in cancer chemotherapy. In this process, oxidative stress and inflammation are considered to be the main mechanisms involved in brain and lung toxicity. The aim of the present work was to study the influence of the amount of protein on some oxidative parameters in the brain and lungs of rats treated with Cisplatin (CP) and N-Acetylcysteine (NAC) as neuroprotectors. Four groups of Wistar rats, each containing six animals, were fed with a protein diet at 7% for 15 days. Thereafter, the groups were given either a unique dose of CP® 5 mg/kg or NAC® 5 mg/kg as follows: group 1 (control), NaCl 0.9% vehicle; group 2, CP; group 3, NAC; and group 4, NAC + CP. The animals were sacrificed immediately after the treatments. Blood samples were collected upon sacrifice and used to measure blood triglycerides and glucose. The brain and lungs of each animal were obtained and used to assay lipid peroxidation (TBARS), glutathione (GSH), serotonin metabolite (5-HIAA), catalase, and the activity of Ca+2, and Mg+2 ATPase using validated methods. TBARS, H2O2, and GSH were found to be significantly decreased in the cortex and cerebellum/medulla oblongata of the groups treated with CP and NAC. The total ATPase showed a significant increase in the lung and cerebellum/medulla oblongata, while 5-HIAA showed the same tendency in the cortex of the same group of animals. The increase in 5-HIAA and ATPase during NAC and CP administration resulted in brain protection. This effect could be even more powerful when membrane fluidity is increased, thus proving the efficacy of combined NAC and CP drug therapy, which appears to be a promising strategy for future chemotherapy in malnourished patients.

The effects of leptin and cannabinoid CB1 receptor agonist/antagonist in cerebral tissues of epileptic rats.

OBJECTIVE: In this study, the effects of leptin, cannabinoid-1 (CB1) receptor agonist ACEA and antagonist AM251, and the interactions between leptin and CB1 receptor agonist/antagonist on oxidant and antioxidant enzymes in the cerebrum, cerebellum, and pedunculus cerebri tissue samples were investigated in the penicillin-induced epileptic model. METHODS: Male Wistar albino rats (n=56) were included in this study. In anesthetized animals, 500 IU penicillin-G potassium was injected into the cortex to induce epileptiform activity. Leptin (1 µg), ACEA (7.5 µg), AM251 (0.25 µg), and the combinations of the leptin+ACEA and leptin+AM251 were administered intracerebroventricularly (i.c.v.) after penicillin injections. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels were measured in the cerebral tissue samples and plasma with the ELISA method. RESULTS: MDA levels increased, while SOD and GPx levels decreased after penicillin injection in the cerebrum and cerebellum. The efficacy of penicillin on SOD, MDA and GPx levels was further enhanced after leptin or AM251 injections. Whereas, ACEA decreased the MDA levels and increased GPx levels compared with the penicillin group. Administration of AM251+leptin did not change any oxidation parameter compared with the AM251. Furthermore, co-administration of ACEA and leptin significantly increased oxidative stress compared with the ACEA-treated group by increasing MDA and decreasing GPx levels. CONCLUSION: It was concluded that leptin reversed the effect of ACEA on oxidative stress. Co-administration of AM251 and leptin did not change oxidative stress compared with the AM251-treated group suggesting AM251 and leptin affect oxidative stress using the same pathways.

Effects of Zinc and N-Acetylcysteine in Damage Caused by Lead Exposure in Young Rats.

This study investigated the toxicity of rats exposed to lead acetate (AcPb) during the second phase of brain development (8-12 days postnatal) in hematological and cerebral parameters. Moreover, the preventive effect of zinc chloride (ZnCl2) and N-acetylcysteine (NAC) was investigated. Pups were injected subcutaneously with saline (0.9% NaCl solution), ZnCl2 (27 mg/kg/day), NAC (5 mg/kg/day) or ZnCl2 plus NAC for 5 days (3rd-7th postnatal days), and with saline (0.9% NaCl solution) or AcPb (7 mg/kg/day) in the five subsequent days (8th-12th postnatal days). Animals were sacrificed 21 days after the last AcPb exposure. Pups exposed to AcPb presented inhibition of blood porphobilinogen-synthase (PBG-synthase) activity without changes in hemoglobin content. ZnCl2 pre-exposure partially prevented PBG-synthase inhibition. Regarding neurotoxicity biomarkers, animals exposed to AcPb presented a decrease in cerebrum acetylcholinesterase (AChE) activity and an increase in Pb accumulation in blood and cerebrum. These changes were prevented by pre-treatment with ZnCl2, NAC, and ZnCl2 plus NAC. AcPb exposure caused no alteration in behavioral tasks. In short, results show that AcPb inhibited the activity of two important enzymatic biomarkers up to 21 days after the end of the exposure. Moreover, ZnCl2 and NAC prevented the alterations induced by AcPb.

Galactose alters markers of oxidative stress and acetylcholinesterase activity in the cerebrum of rats: protective role of antioxidants.

We evaluated the in vitro effects of galactose at 0.1, 3.0, 5.0 and 10.0 mM on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content, protein carbonyl content, on the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and on acetylcholinesterase (AChE) activity in the cerebral cortex, cerebellum and hippocampus of rats. We also investigated the influence of the antioxidants (each at 1 mM), α-tocopherol, ascorbic acid and glutathione, on the effects elicited by galactose on the parameters tested. Results showed that galactose, at a concentration of 3.0 mM, enhanced TBA-RS levels in the hippocampus, cerebral cortex and cerebellum of rats. In the cerebral cortex, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and protein carbonyl content, and at 10.0 mM increased CAT activity and decreased AChE activity. In the cerebellum, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS, SOD and GSH-Px activities. In the hippocampus, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and CAT activity and at 10.0 mM decreased GSH-Px. Data showed that at the pathologically high concentration (greater than 5.0 mM), galactose induces lipid peroxidation, protein carbonylation, alters antioxidant defenses in the cerebrum, and also alters cholinesterase activity. Trolox, ascorbic acid and glutathione addition prevented the majority of alterations in oxidative stress parameters and the decrease in AChE activity that were caused by galactose. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by galactose.

Gabaergic control of anxiety-like behavior, but not food intake, induced by ghrelin in the intermediate medial mesopallium of the neonatal chick.

Ghrelin (Grh) is an endogenous ligand of the growth hormone secretagogue receptor. In neonatal chicks, central Ghr induces anxiogenic-like behavior but strongly inhibits food intake. The intermediate medial mesopallium (IMM) of the chick forebrain has been identified to be a site of the memory formation, and the modulation of the GABAA receptors that are present here modifies the expression of behavior. Thus, the GABAergic system may constitute a central pathway for Ghr action in regulating the processes of food intake and stress-related behaviors. Therefore, we investigated if the effect of systemic administration of bicuculline (GABAA receptor antagonist) and diazepam (benzodiazepine receptor agonist) on the anxiety in an Open Field test and inhibition in food intake induced by Grh (30pmol) when injected into IMM, were mediated by GABAergic transmission. In Open Field test, bicuculline was able to block the anxiogenic-like behavior induced by Ghr, whereas diazepam did not produce it. However, the co-administration of bicuculline or diazepam plus Ghr did not show any change in food intake at 30, 60 and 120min after injection compared to Ghr alone. Our results indicate for the first time that Ghr, injected into the forebrain IMM area, induces an anxiogenic-like behavior, which was blocked by bicuculline but not diazepam, thus suggesting that Ghr plays an important role in the response pattern to acute stressor, involving the possible participation of the GABAergic system. Nevertheless, as neither drug affected the hypophagia induced by intra-IMM Ghr, this suggests that it may be mediated by different mechanisms.

The impact of gene expression analysis on evolving views of avian brain organization.

Recent studies have presented data on adult and developing avian brain organization. Jarvis et al. ([2013] J Comp Neurol. 521:3614-3665) identify four pallial and two subpallial gene expression domains and demonstrate that the mesopallium and adjoining divisions of the hyperpallium (hyperpallium intercalatum and hyperpallium densocellulare), have very similar gene expression profiles to each other, distinct from those of the nidopallium, the arcopallium, and the more distant divisions of the hyperpallium (hyperpallium apicale). The study proposes an update of the current nomenclature (Jarvis et al. [2005] Nat Rev Neurosci. 6:151-159). The authors perform densitometric quantifications of the in situ expression of 50 selected genes, use correlations of distances between vectors that represent these gene expression patterns within the 23 avian brain regions of their study, and group them according to similarity in their expression profiles. The generated cluster tree further supports their argument for a new terminology. The authors hypothesize that the mesopallium and adjoining divisions of the hyperpallium have a common developmental origin, and in the accompanying paper (Chen et al. [2013] J Comp Neurol. 521:3666-3701) show that these structures/subdivisions initially form continuous gene expression domains. With subsequent development these domains fold into distinct subdivisions in the dorsal and ventral avian pallium, forming mirror images to each other. Jarvis et al. ([2013] J Comp Neurol. 521:3614-3665) also demonstrate interesting principles of the functional organization of the avian brain by showing that specific sensory stimulation or motor behavior elicits gene expression in functional units perpendicular to the axis of the gene expression reversal and compare their arrangements and cell types with mammalian cortical columns.

La somatostatina en el núcleo del tracto solitario comisural modula la retención de glucosa cerebral postestimulación anóxica de los quimioreceptores carotídeos en ratas / Somatostatin into the Commissural Nucleus Tractus Solitarius Modulates Brain Glucose Retention Post- Anoxic Stimulation of the Carotid Chemoreceptor in Rats

El núcleo del tracto solitario comisural (NTSc) es el centro de relevo de las fibras aferentes procedentes de los baro y quimiorreceptores carotídeos, por lo que modula la presión arterial y la glucemia ante los estímulos en dichos receptores. La estimulación anóxica con cianuro de sodio (NaCN) en los cuerpos carotídeos produce una respuesta hiperglucemiante. La somatostatina (SS) inhibe la secreción de la hormona del crecimiento y del glucagón lo que produce un efecto hipoglucemiante. La SS y sus receptores en el NTS tienen un efecto inhibidor. Se postula que la somatostatina modula la respuesta hiperglucemiante después de la estimulación de los quimiorreceptores carotídeos (QRC) con NaCN. En este trabajo, la infunsión de SS en el NTSc 4 min antes del estímulo anóxico de los QRC, disminuyó el reflejo hiperglucemiante y la retención de glucosa cerebral a los 10 min del estímulo anóxico. Se concluye que la SS en el NTSc modula la respuesta hiperglucemiante y la retención de glucosa cerebral post-estimulación anóxica de los cuerpos carotídeos en ratas(AU)

The commissural nucleus of the solitary tract (NTSc) is the relay center of the afferents fibers from the carotid baro and chemoreceptors, so that modulates blood pressure and blood sugar to stimuli in these receptors. Anoxic stimulation with sodium cyanide (NaCN) in the carotid bodies produces a hyperglycemic response. Somatostatin (SS) inhibits secretion of growth hormone and glucagon producing a hypoglycemic effect. The SS and its receptors in the NTS have an inhibitory effect. It is postulated that somatostatin modulates the hyperglycaemic response after stimulation of carotid chemoreceptors (QRC) with NaCN. In this work, the SS infusion into NTSc 4 min before the anoxic stimulation of the QRC, decreased the hyperglycemic reflex and cerebral glucose retention after 10 min of anoxic stimulus. We conclude that SS modulates the NTSc hyperglycemic response and brain glucose retention post-anoxic stimulation of the carotid bodies in rats(AU)

La somatostatina en el núcleo del tracto solitario comisural modula la retención de glucosa cerebral postestimulación anóxica de los quimioreceptores carotídeos en ratas / Somatostatin into the Commissural Nucleus Tractus Solitarius Modulates Brain Glucose Retention Post- Anoxic Stimulation of the Carotid Chemoreceptor in Rats

El núcleo del tracto solitario comisural (NTSc) es el centro de relevo de las fibras aferentes procedentes de los baro y quimiorreceptores carotídeos, por lo que modula la presión arterial y la glucemia ante los estímulos en dichos receptores. La estimulación anóxica con cianuro de sodio (NaCN) en los cuerpos carotídeos produce una respuesta hiperglucemiante. La somatostatina (SS) inhibe la secreción de la hormona del crecimiento y del glucagón lo que produce un efecto hipoglucemiante. La SS y sus receptores en el NTS tienen un efecto inhibidor. Se postula que la somatostatina modula la respuesta hiperglucemiante después de la estimulación de los quimiorreceptores carotídeos (QRC) con NaCN. En este trabajo, la infunsión de SS en el NTSc 4 min antes del estímulo anóxico de los QRC, disminuyó el reflejo hiperglucemiante y la retención de glucosa cerebral a los 10 min del estímulo anóxico. Se concluye que la SS en el NTSc modula la respuesta hiperglucemiante y la retención de glucosa cerebral post-estimulación anóxica de los cuerpos carotídeos en ratas

The commissural nucleus of the solitary tract (NTSc) is the relay center of the afferents fibers from the carotid baro and chemoreceptors, so that modulates blood pressure and blood sugar to stimuli in these receptors. Anoxic stimulation with sodium cyanide (NaCN) in the carotid bodies produces a hyperglycemic response. Somatostatin (SS) inhibits secretion of growth hormone and glucagon producing a hypoglycemic effect. The SS and its receptors in the NTS have an inhibitory effect. It is postulated that somatostatin modulates the hyperglycaemic response after stimulation of carotid chemoreceptors (QRC) with NaCN. In this work, the SS infusion into NTSc 4 min before the anoxic stimulation of the QRC, decreased the hyperglycemic reflex and cerebral glucose retention after 10 min of anoxic stimulus. We conclude that SS modulates the NTSc hyperglycemic response and brain glucose retention post-anoxic stimulation of the carotid bodies in rats

Diffusion tensor imaging-derived measures of fractional anisotropy across the pyramidal tract are influenced by the cerebral hemisphere but not by gender in young healthy volunteers: a split-plot factorial analysis of variance.

BACKGROUND: Diffusion tensor imaging (DTI) permits quantitative examination within the pyramidal tract (PT) by measuring fractional anisotropy (FA). To the best of our knowledge, the inter-variability measures of FA along the PT remain unexplained. A clear understanding of these reference values would help radiologists and neuroscientists to understand normality as well as to detect early pathophysiologic changes of brain diseases. The aim of our study was to calculate the variability of the FA at eleven anatomical landmarks along the PT and the influences of gender and cerebral hemisphere in these measurements in a sample of young, healthy volunteers. METHODS: A retrospective, cross-sectional study was performed in twenty-three right-handed healthy volunteers who underwent magnetic resonance evaluation of the brain. Mean FA values from eleven anatomical landmarks across the PT (at centrum semiovale, corona radiata, posterior limb of internal capsule (PLIC), mesencephalon, pons, and medulla oblongata) were evaluated using split-plot factorial analysis of variance (ANOVA). RESULTS: We found a significant interaction effect between anatomical landmark and cerebral hemisphere (F (10, 32) = 4.516, P = 0.001; Wilks' Lambda 0.415, with a large effect size (partial η(2) = 0.585)). The influence of gender and age was non-significant. On average, the midbrain and PLIC FA values were higher than pons and medulla oblongata values; centrum semiovale measurements were higher than those of the corona radiata but lower than PLIC. CONCLUSIONS: There is a normal variability of FA measurements along PT in healthy individuals, which is influenced by regions of interest location (anatomical landmarks) and cerebral hemisphere. FA measurements should be reported for comparing same-side and same-landmark PT to help avoid comparisons with the contralateral PT; ideally, normative values should exist for a clinically significant age group. A standardized package of selected DTI processing tools would allow DTI processing to be routinely performed in clinical settings.

Anestesia, demencias y enfermedad de Alzheimer: ¿coincidencia o certeza? / Anesthesia, dementia and Alzheimer's disease: coincidence or certainty?

Existe creciente evidencia derivada de modelos experimentales in vitro, cultivos celulares y modelos animales que sugiere el efecto de la anestesia sobre la degeneración neuronal y una interacción entre la cirugía, la anestesia y la neuropatología denominada Alzheimer. También existe la firme creencia de que los ancianos corren el riesgo de sufrir deterioro cognitivo transitorio, aunque también puede ser persistente, después de haber sido sometidos a una cirugía mayor, y ese deterioro puede estar asociado a muerte o debilidad. En este trabajo revisamos brevemente los fundamentos básicos de la enfermedad de Alzheimer y su interacción con la anestesia general, y los pocos datos clínicos en humanos que han sido utilizados para proponer una posible asociación entre la anestesia general y las demencias.

Anestesia, demencias y enfermedad de Alzheimer: ¿coincidencia o certeza? / Anesthesia, dementia and Alzheimers disease: coincidence or certainty?

Existe creciente evidencia derivada de modelos experimentales in vitro, cultivos celulares y modelos animales que sugiere el efecto de la anestesia sobre la degeneración neuronal y una interacción entre la cirugía, la anestesia y la neuropatología denominada Alzheimer. También existe la firme creencia de que los ancianos corren el riesgo de sufrir deterioro cognitivo transitorio, aunque también puede ser persistente, después de haber sido sometidos a una cirugía mayor, y ese deterioro puede estar asociado a muerte o debilidad. En este trabajo revisamos brevemente los fundamentos básicos de la enfermedad de Alzheimer y su interacción con la anestesia general, y los pocos datos clínicos en humanos que han sido utilizados para proponer una posible asociación entre la anestesia general y las demencias. (AU)

Assessment of neurotoxicity of monocrotaline, an alkaloid extracted from Crotalaria retusa in astrocyte/neuron co-culture system.

Studies have shown cases of poisoning with plants from the genus Crotalaria (Leguminosae) mainly in animals. They induce damages in the central nervous system (CNS), which has been attributed to toxic effects of the pyrrolizidine alkaloid (PA) monocrotaline (MCT). Previously we demonstrated that both MCT and dehydromonocrotaline (DHMC), its main active metabolite, induce changes in the levels and patterns of expression of the main protein from astrocyte cytoskeleton, glial fibrillary acidic protein (GFAP). In this study we investigated the effect of MCT on rat cortical astrocyte/neuron primary co-cultures. Primary cultures were exposed to 10 or 100 µM MCT. The MTT test and the measurement of LDH activity on the culture medium revealed that after 24h exposure MCT was not cytotoxic to neuron/astrocyte cells. However, the cell viability after 72 h treatment decreased in 10-20%, and the LDH levels in the culture medium increased at a rate of 12% and 23%, in cultures exposed to 10 or 100 µM MCT. Rosenfeld staining showed vacuolization and increase in cell body in astrocytes after MCT exposure. Immunocytochemistry and Western blot analyses revealed changes on pattern of GFAP and ßIII-tubulin expression and steady state levels after MCT treatment, with a dose and time dependent intense down regulation and depolarization of neuronal ßIII-tubulin. Moreover, treatment with 100 µM MCT for 12h induced GSH depletion, which was not seen when cytochrome P450 enzyme system was inhibited indicating that it is involved in MCT induced cytotoxicity in CNS cells.

Systematization, distribuiton and Territory of the rostral cerebral artery on the brain surface in chinchilla

The present study has analyzed thirty chinchilla (Chinchilla lanigera) brains, injected with latex, aiming tosystematize and describe the distribution and the vascularization territories of the rostral cerebral artery. Therostral cerebral artery was the terminal branch of the terminal branch, right and left, of the basilar artery,projected from the emittion of the middle cerebral artery, rostromedially, crossing dorsally the optic nerve untilit reaches the cerebral longitudinal fissure, ventrally. Its branches were distributed mostly on the paleopallium,supplying the olfactory trigone, the medial olfactory tract, the olfactory peduncle and the olfactory bulb.The branches to the neopallium vascularized the entire medial surface, except for the tenctorial part of it, thefrontal pole and a zone that was extended from the frontal to the occipital poles, medially to the vallecula,on the convex surface of the cerebral hemisphere. The first collateral branch of the rostral cerebral artery wasthe medial branch, which entered into the longitudinal fissure of the brain and continued as rostral interhemisphericartery. The rostral cerebral artery continued rostrally emitting central branches and the medialand lateral arteries of the olfactory bulb, to the paleopallial region of the chinchilla brain. After the emittion ofthe medial artery of the olfactory bulb, the rostral cerebral artery continued to follow the cerebral longitudinalfissure, as internal ethmoidal artery, its terminal branch.

Acute administration of 5-oxoproline induces oxidative damage to lipids and proteins and impairs antioxidant defenses in cerebral cortex and cerebellum of young rats.

5-Oxoproline accumulates in glutathione synthetase deficiency, an autossomic recessive inherited disorder clinically characterized by hemolytic anemia, metabolic acidosis, and severe neurological symptoms whose mechanisms are poorly known. In the present study we investigated the effects of acute subcutaneous administration of 5-oxoproline to verify whether oxidative stress is elicited by this metabolite in vivo in cerebral cortex and cerebellum of 14-day-old rats. Our results showed that the acute administration of 5-oxoproline is able to promote both lipid and protein oxidation, to impair brain antioxidant defenses, to alter SH/SS ratio and to enhance hydrogen peroxide content, thus promoting oxidative stress in vivo, a mechanism that may be involved in the neuropathology of gluthatione synthetase deficiency.

Methylphenidate treatment increases Na(+), K (+)-ATPase activity in the cerebrum of young and adult rats.

Methylphenidate is a central nervous system stimulant used for the treatment of attention-deficit hyperactivity disorder. Na(+), K(+)-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that methylphenidate effects on central nervous system metabolism are poorly known and that Na(+), K(+)-ATPase is essential to normal brain function, the purpose of this study was to evaluate the effect of this drug on Na(+), K(+)-ATPase activity in the cerebrum of young and adult rats. For acute administration, a single injection of methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline was given to rats on postnatal day 25 or postnatal day 60, in the young and adult groups, respectively. For chronic administration, methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline injections were given to young rats starting at postnatal day 25 once daily for 28 days. In adult rats, the same regimen was performed starting at postnatal day 60. Our results showed that acute methylphenidate administration increased Na(+), K(+)-ATPase activity in hippocampus, prefrontal cortex, and striatum of young and adult rats. In young rats, chronic administration of methylphenidate also enhanced Na(+), K(+)-ATPase activity in hippocampus and prefrontal cortex, but not in striatum. When tested in adult rats, Na(+), K(+)-ATPase activity was increased in all cerebral structures studied. The present findings suggest that increased Na(+), K(+)-ATPase activity may be associated with neuronal excitability caused by methylphenidate.

Propriedades Redox de canais de potássio mitocondriais ATP-sensíveis em cérebro e seu efeito neuroprotetor em excitotoxicidade / Redox properties of brain mitochondrial ATP-sensitive potassium channels and neuroprotective effects in excitotoxicity

Muitos estudos demonstram que a abertura de canais de ´KPOT.+` mitocondriais sensíveis à ATP (mito´K ind.ATP`) previnem contra danos promovidos por isquemia/reperfusao em coração. Em geral, esta proteçao envolve mudanças no estado redox mitocondrial. Em cérebro, sabe-se que agonistas farmacológicos de mito´K ind.ATP` também protegem em modelo de isquemia/reperfusão. Entretanto, os mecanismos envolvidos na prevenção de danos em cérebro ainda não estão claros. 0 objetivo principal deste trabalho é compreender os efeitos de canais de K+ mitocondriais ATP-sensíveis em tecido cerebral e os mecanismos pelos quais a sua ativação pode proteger contra danos promovidos por excitotoxicidade, uma das principais consequências de um evento isquêmico em cerebro. Neste contexto, demonstramos a proteção pelo mito´K ind.ATP` em modelo de excitotoxicidade induzida pela ativação direta de receptores NMDA, utilizando cultura de células granulosas de cerebelo. Paralelamente a essa proteção, verificamos que a ativação de mito´K ind.ATP` reduz a geração de espécies reativas de oxigênio (ROS)...

Purificación de IgY contra la subunidad NR3 del receptor NMDA de cerebro de rata / Purification of IgY against the NR3 subunit of the rat brain NMDA receptor

Objetivo. Obtener anticuerpos tipo IgY contra péptidos sintéticos de las subunidades NR3A y NR3B del receptor NMDA de ratas, para reconocer y seguir la expresión de estas subunidades en extractos de cerebro de rata de diferentes edades. Materiales y métodos. Se diseñaron dos péptidos empleando los sistemas de la base de datos Entrez y el programa ClustalWPBIL de alineamientos múltiples contra las subunidades NR3A y NR3B del receptor NMDA; una vez sintetizados por el método SSPS-fmoc fueron utilizados para inocular gallinas (Gallus gallus, variedad Hy Line Brown) de 16 semanas de edad; al cabo de 57 días postinoculación se purificó IgY específica y se enfrentaron a extractos de cerebro de rata postnatal y adulta. Resultados. Se detectaron las subunidades NR3A y NR3B y se relacionó su expresión con la edad del animal; siendo mayor la expresión de la subunidad NR3A en extracto de cerebro de rata postnatal. No se encontró diferencia marcada en la expresión de la subunidad NR3B en las edades mencionadas. Conclusiones. Esta es la primera investigación que emplea proteína nativa para el reconocimiento de la subunidad NR3 del receptor NMDA, lo cual muestra la especificidad de los anticuerpos generados y contribuye con el entendimiento de las funciones de este receptor y su relación con la regulación de la memoria espacial.

Differential expression of E-cadherin gene in human neuroepithelial tumors

Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architecture. Structural defects or loss of expression of E-cadherin have been reported as a common feature in several human cancer types. This study aimed to evaluate the expression of E-cadherin and their correlation with clinical features in microdissected brain tumor samples from 81 patients, divided into 62 astrocytic tumors grades I to IV and 19 medulloblastomas, and from 5 white matter non-neoplasic brain tissue samples. E-cadherin (CDH1) gene expression was analyzed by quantitative real-time polymerase chain reaction. Mann-Whitney, Kruskal-Wallis, Kaplan-Meir, and log-rank tests were performed for statistical analyses. We observed a decrease in expression among pathological grades of neuroepithelial tumors. Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than did neuroepithelial tumors. Expression of E-cadherin gene was higher in astrocytic than embryonal tumors (P = 0.0168). Low-grade malignancy astrocytomas (grades I-II) showed higher CDH1 expression than did high-grade malignancy astrocytomas (grades III-IV) and medulloblastomas (P < 0.0001). Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than grade I malignancy astrocytomas, considered as benign tumors (P = 0.0473). These results suggest that a decrease in E-cadherin gene expression level in high-grade neuroepithelial tumors may be a hallmark of malignancy in dedifferentiated tumors and that it may be possibly correlated with their progression and dissemination.

Capítulo 12. El metabolismo en situaciones específicas

El metabolismo es el conjunto de reacciones enzimáticas que tienen lugar en la célula de todos los organismos vivos, y, se caracteriza, por ser un proceso finamente controlado y con un nivel alto de integración entre todas las vías metabólicas. En los organismos pluricelulares existe además una cooperación entre los diferentes órganos para lograr un nivel de integración en el organismo en su conjunto y poder responder así a los cambios del medio interno y del ambiente. De esta manera en el ser humano cada órgano y tejido se ha especializado a lo largo del proceso evolutivo en llevar a cabo procesos metabólicos y funciones que son útiles para otros órganos y en circunstancias cuando se requiere una adaptación bastante rápida para mantener las funciones vitales. Así el tejido adiposo se ha especializado en el almacenamiento de triacilgliceroles para utilizar posteriormente esta reserva en las condiciones de ayuno, de corta o larga duración, y en el ejercicio físico ; en el hígado existe una reserva de glucógeno muy importante, capaz de movilizarse en las condiciones de ayuno por ejemplo y aportar glucosa a la sangre para ser utilizada por muchos órganos, entre estos de manera especial el cerebro; el músculo almacena también glucógeno que en condiciones de ejercicio se degrada y genera finalmente gran cantidad de glucosa 6-P para ser utilizada como combustible por la vía de la glucólisis , pero solo en este órgano; la vía de la gluconeogénesis es muy activa en el hígado a partir del glicerol que recibe del tejido adiposo y de aminoácidos procedentes del músculo, sustratos de la vía a partir de los cuales se sintetiza glucosa para su utilización por otros tejidos. El cerebro por otro lado es un órgano que depende del suministro de glucosa por la sangre aunque en condiciones de ayuno puede utilizar también cuerpos cetónicos...(AU)