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Inducing carotid body anoxia through the administration of cyanide can result in oxygen deprivation. The lack of oxygen activates cellular responses in specific regions of the central nervous system, including the Nucleus Tractus Solitarius, hypothalamus, hippocampus, and amygdala, which are regulated by afferent pathways from chemosensitive receptors. These receptors are modulated by the brain-derived neurotrophic factor receptor TrkB. Oxygen deprivation can cause neuroinflammation in the brain regions that are activated by the afferent pathways from the chemosensitive carotid body. To investigate how microglia, a type of immune cell in the brain, respond to an anoxic environment resulting from the administration of NaCN, we studied the effects of blocking the TrkB receptor on this cell-type response. Male Wistar rats were anesthetized, and a dose of NaCN was injected into their carotid sinus to induce anoxia. Prior to the anoxic stimulus, the rats were given an intracerebroventricular (icv) infusion of either K252a, a TrkB receptor inhibitor, BDNF, or an artificial cerebrospinal fluid (aCSF). After the anoxic stimulus, the rats were perfused with paraformaldehyde, and their brains were processed for microglia immunohistochemistry. The results indicated that the anoxic stimulation caused an increase in the number of reactive microglial cells in the hypothalamic arcuate, basolateral amygdala, and dentate gyrus of the hippocampus. However, the infusion of the K252a TrkB receptor inhibitor prevented microglial activation in these regions.
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The hippocampus is a brain region crucially involved in regulating stress responses and highly sensitive to environmental changes, with elevated proliferative and adaptive activity of neurons and glial cells. Despite the prevalence of environmental noise as a stressor, its effects on hippocampal cytoarchitecture remain largely unknown. In this study, we aimed to investigate the impact of acoustic stress on hippocampal proliferation and glial cytoarchitecture in adult male rats, using environmental noise as a stress model. After 21 days of noise exposure, our results showed abnormal cellular proliferation in the hippocampus, with an inverse effect on the proliferation ratios of astrocytes and microglia. Both cell lineages also displayed atrophic morphologies with fewer processes and lower densities in the noise-stressed animals. Our findings suggest that, stress not only affects neurogenesis and neuronal death in the hippocampus, but also the proliferation ratio, cell density, and morphology of glial cells, potentially triggering an inflammatory-like response that compromises their homeostatic and repair functions.
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Hipocampo , Neuroglía , Ratas , Masculino , Animales , Hipocampo/metabolismo , Neuronas/metabolismo , Astrocitos/metabolismo , Microglía/metabolismo , Neurogénesis/fisiologíaRESUMEN
The c-fos gene was first described as a proto-oncogene responsible for the induction of bone tumors. A few decades ago, activation of the protein product c-fos was reported in the brain after seizures and other noxious stimuli. Since then, multiple studies have used c-fos as a brain activity marker. Although it has been attributed to neurons, growing evidence demonstrates that c-fos expression in the brain may also include glial cells. In this review, we collect data showing that glial cells also express this proto-oncogene. We present evidence demonstrating that at least astrocytes, oligodendrocytes, and microglia express this immediate early gene (IEG). Unlike neurons, whose expression changes used to be associated with depolarization, glial cells seem to express the c-fos proto-oncogene under the influence of proliferation, differentiation, growth, inflammation, repair, damage, plasticity, and other conditions. The collected evidence provides a complementary view of c-fos as an activity marker and urges the introduction of the glial cell perspective into brain activity studies. This glial cell view may provide additional information related to the brain microenvironment that is difficult to obtain from the isolated neuron paradigm. Thus, it is highly recommended that detection techniques are improved in order to better differentiate the phenotypes expressing c-fos in the brain and to elucidate the specific roles of c-fos expression in glial cells.
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INTRODUCTION: Noise is one of the main sources of discomfort in modern societies. It affects physiology, behavior, and cognition of exposed subjects. Although the effects of noise on cognition are well known, gender role in noise-cognition relationship remains controversial. AIM: We analyzed the effects of noise on the ability of male and female rats to execute the Radial Arm Water Maze (RAWM) paradigm. MATERIALS AND METHODS: Male and female Wistar rats were exposed to noise for 3 weeks, and the cognitive effects were assessed at the end of the exposure. RAWM execution included a three-day training phase and a reversal-learning phase conducted on the fourth day. Escape latency, reference memory errors, and working memory errors were quantified and compared between exposed and non-exposed subjects. RESULTS: We found that male rats were in general more affected by noise. Execution during the three-day learning phase evidenced that male exposed rats employed significantly more time to acquire the task than the non-exposed. On the other hand, the exposed females solved the paradigm in latencies similar to control rats. Both, males and females diminished their capacity to execute on the fourth day when re-learning abilities were tested. CONCLUSION: We conclude that male rats might be less tolerable to noise compared to female ones and that spatial learning may be a cognitive function comparably more vulnerable to noise.
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Aprendizaje por Laberinto , Ruido/efectos adversos , Animales , Cognición , Femenino , Masculino , Memoria a Corto Plazo , Ratas , Ratas Wistar , Factores Sexuales , NataciónRESUMEN
Prolonged or intense exposure to environmental noise (EN) has been associated with a number of changes in auditory organs as well as other brain structures. Notably, males and females have shown different susceptibilities to acoustic damage as well as different responses to environmental stressors. Rodent models have evidence of sex-specific changes in brain structures involved in noise and sound processing. As a common effect, experimental models have demonstrated that dendrite arborizations reconfigure in response to aversive conditions in several brain regions. Here, we examined the effect of chronic noise on dendritic reorganization and c-Fos expression patterns of both sexes. During 21 days male and female rats were exposed to a rats' audiogram-fitted adaptation of a noisy environment. Golgi-Cox and c-Fos staining were performed at auditory cortices (AC) and hippocampal regions. Sholl analysis and c-Fos counts were conducted for evidence of intersex differences. In addition, pro-BDNF serum levels were also measured. We found different patterns of c-Fos expression in hippocampus and AC. While in AC expression levels showed rapid and intense increases starting at 2 h, hippocampal areas showed slower rises that reached the highest levels at 21 days. Sholl analysis also evidenced regional differences in response to noise. Dendritic trees were reduced after 21 days in hippocampus but not in AC. Meanwhile, pro-BDNF levels augmented after EN exposure. In all analyzed variables, exposed males were the most affected. These findings suggest that noise may exert differential effects on male and female brains and that males could be more vulnerable to the chronic effects of noise.
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Corteza Auditiva/metabolismo , Factor Neurotrófico Derivado del Encéfalo/sangre , Hipocampo/metabolismo , Plasticidad Neuronal , Ruido/efectos adversos , Precursores de Proteínas/sangre , Proteínas Proto-Oncogénicas c-fos/metabolismo , Animales , Corteza Auditiva/patología , Femenino , Hipocampo/patología , Masculino , Ratas Wistar , Caracteres Sexuales , Estrés FisiológicoRESUMEN
BACKGROUND: Chronic exposure to noise induces changes on the central nervous system of exposed animals. Those changes affect not only the auditory system but also other structures indirectly related to audition. The hippocampus of young animals represents a potential target for these effects because of its essential role in individuals' adaptation to environmental challenges. OBJECTIVE: The aim of the present study was to evaluate hippocampus vulnerability, assessing astrocytic morphology in an experimental model of environmental noise (EN) applied to rats in pre-pubescent stage. MATERIALS AND METHODS: Weaned Wistar male rats were subjected to EN adapted to the rats' audiogram for 15 days, 24 h daily. Once completed, plasmatic corticosterone (CORT) concentration was quantified, and immunohistochemistry for glial fibrillary acidic protein was taken in hippocampal DG, CA3, and CA1 subareas. Immunopositive cells and astrocyte arborizations were counted and compared between groups. RESULTS: The rats subjected to noise exhibited enlarged length of astrocytes arborizations in all hippocampal subareas. Those changes were accompanied by a marked rise in serum CORT levels. CONCLUSIONS: These findings confirm hippocampal vulnerability to EN and suggest that glial cells may play an important role in the adaptation of developing the participants to noise exposure.
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Astrocitos/patología , Exposición a Riesgos Ambientales/efectos adversos , Hipocampo/citología , Ruido/efectos adversos , Animales , Corticosterona/sangre , Proteína Ácida Fibrilar de la Glía/metabolismo , Inmunohistoquímica , Masculino , Ratas , Ratas WistarRESUMEN
The repeated injection of insulin (unconditioned stimulus, UCS) immediately followed by exposure to sensory stimulation (e.g. sound or odor; conditioned stimulus, CS) results in a learned conditioned reflex in which the exposure to the CS alone lowers blood glucose. The brain regions participating in this hypoglycemic Pavlovian response remain unknown. Here we investigate if nitric oxide (NO) in the nucleus tractus solitarius (NTS), a nucleus known to be involved in glucose homeostasis, participates in this hypoglycemic reflex. Insulin injections (UCS) were paired with exposure to menthol odor (CS). After 8-10 reinforcements (4-5days training), rats acquire the learned hypoglycemic response. An increase in c-Fos expression was observed in the NTS, the ventrolateral hypothalamic nucleus (VLH) and other brain regions of conditioned rats. Microinjections of 3-(5'-hydroxymethyl-2'furyl)-1-benzyl indazole (YC-1) a stimulator of soluble guanylate cyclase (sGC) into NTS before the UCS accelerated the acquisition of the learned hypoglycemic response; 5-6 reinforcement produced pronounced glucose drop when exposed to the CS. In contrast, an inhibitor of NO synthase (NOS) Nω-Nitro-l-arginine methyl ester (L-NAME) in the NTS prolonged the required training period (11-15 reinforcements) to obtain the hypoglycemic reflex, and reduced the glycemic response. The number of c-Fos expressing cells in the NTS and VLH in rats receiving YC-1was significantly higher than that observed in rats receiving L-NAME. These findings suggest that NO-cGMP-PKG signaling in the NTS can modify the acquisition of conditioned hypoglycemia, and suggests that this nucleus directly participates in this reflex.
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Condicionamiento Clásico/fisiología , Hipoglucemia/metabolismo , Óxido Nítrico/metabolismo , Núcleo Solitario/metabolismo , Animales , Inhibidores Enzimáticos/farmacología , Glucosa/metabolismo , Homeostasis/fisiología , Indazoles/farmacología , Insulina/administración & dosificación , Masculino , Mentol , NG-Nitroarginina Metil Éster/farmacología , Nootrópicos/farmacología , Percepción Olfatoria/fisiología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Distribución Aleatoria , Ratas WistarRESUMEN
INTRODUCTION: Gastroschisis is a malformation of the abdominal wall that is corrected by surgery and requires special hospital care, such as immobilisation, dietary restriction and separation from the mother for a variable period of time, among others. To analyse the possible cognitive repercussions, the Bayley III test was administered to 14 children. SUBJECTS AND METHODS: The study was conducted with seven cases (born with gastroschisis) and seven controls, in civil hospitals in Guadalajara, over the period January-April 2013. RESULTS: No evidence of retardation was found in the cases in the cognition, language and motor conduct assessments, whereas in those associated with socio-emotional and adaptive behaviour the scores favoured the control group. This shows that the latter have better adaptation and interaction strategies with respect to the cases group. CONCLUSIONS: Gastroschisis will not affect later neurodevelopment, at least in this group which presented only this abnormality and deficits that can be explained by their perinatal circumstances. Nevertheless, this prognosis cannot be generalised to other cases with a more severe clinical picture, a longer stay in hospital and associated comorbidity. In any case, it is important to inform the parents as of the prenatal stage about the expected consequences of this pathology.
TITLE: Evaluacion cognitiva en niños que presentaron gastrosquisis: estudio de casos y controles.Introduccion. La gastrosquisis es una malformacion de la pared abdominal que se corrige mediante cirugia y requiere cuidados hospitalarios especiales, como inmovilizacion, restriccion alimenticia y separacion de la madre durante tiempo variable, entre otros; para analizar las posibles repercusiones cognitivas se aplico la prueba de Bayley III a 14 niños. Sujetos y metodos. Siete casos (nacidos con gastrosquisis) y siete controles, en los hospitales civiles de Guadalajara, en el periodo enero-abril de 2013. Resultados. Los casos no evidenciaron retraso en las evaluaciones relacionadas con la cognicion, el lenguaje y la conducta motora, en tanto que en las asociadas a la conducta socioemocional y adaptativa las puntuaciones favorecieron al grupo control, lo que refleja que poseen mejores estrategias de adaptacion e interaccion respecto al grupo de casos. Conclusiones. La gastrosquisis no afectara el neurodesarrollo ulterior, por lo menos en este grupo que presento esta unica anormalidad y deficits explicables por sus circunstancias perinatales, sin que este pronostico pueda generalizarse a otros casos con un cuadro clinico mas grave, mayor duracion de la estancia hospitalaria y comorbilidad asociada. De cualquier forma, es importante informar a los padres desde la etapa prenatal respecto a las consecuencias esperadas de esta patologia.
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Cognición , Gastrosquisis/psicología , Estudios de Casos y Controles , Desarrollo Infantil , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Sistema Nervioso/crecimiento & desarrollo , Pruebas NeuropsicológicasRESUMEN
In this study, we exposed adult rats to chronic variable stress (CVS) and tested the hypothesis that previous early-life exposure to stress changes the manner in which older subjects respond to aversive conditions. To this end, we analyzed the cytogenic changes in the hippocampus and hippocampal-dependent spatial learning performance. The experiments were performed on 18-month-old male rats divided into four groups as follows: Control (old rats under standard laboratory conditions), Early-life stress (ELS; old rats who were exposed to environmental noise from postnatal days, PNDs 21-35), CVS + ELS (old rats exposed to a chronic stress protocol who were previously exposed to the early-life noise stress) and CVS (old rats who were exposed only to the chronic stress protocol). The Morris Water Maze (MWM) was employed to evaluate the spatial learning abilities of the rats at the end of the experiment. Immunohistochemistry against 5'Bromodeoxyuridine (BrdU) and glial fibrillar acidic protein (GFAP) was also conducted in the DG, CA1, CA2 and CA3 regions of the hippocampus. We confocally analyzed the cytogenic (BrdU-labeled cells) and astrogenic (BrdU + GFAP-labeled cells) changes produced by these conditions. Using this procedure, we found that stress diminished the total number of BrdU+ cells over the main proliferative area of the hippocampus (i.e., the dentate gyrus, DG) but increased the astrocyte phenotypes (GFAP + BrdU). The depleted BrdU+ cells were restored when the senile rats also experienced stress at the early stages of life. The MWM assessment demonstrated that stress also impairs the ability of the rats to learn the task. This impairment was not present when the stressful experience was preceded by the early-life exposure. Thus, our results support the idea that previous exposure to mild stressing agents may have beneficial effects on aged subjects.
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Carotid body chemoreceptors function as glucose sensors and contribute to glucose homeostasis. The nucleus tractus solitarii (NTS) is the first central nervous system (CNS) nuclei for processing of information arising in the carotid body. Here, we microinjected a nitric oxide (NO) donor sodium nitroprusside (SNP), an NO-independent activator of the soluble guanylyl cyclase (sGC) (YC1) or an NO-synthase (NOS) inhibitor Nω-nitro-l-arginine methyl ester (L-NAME) into the commissural NTS (cNTS) before carotid chemoreceptor anoxic stimulation and measured arterial glucose and the expression of Fos-like immunoreactivity (Fos-ir). Male Wistar rats (250-300 g) were anesthetized, and the carotid sinus was vascularly isolated. Either artificial cerebrospinal fluid (aCSF), SNP, YC1 or L-NAME were stereotaxically injected into the cNTS. The SNP and YC1 infused into the cNTS before carotid chemoreceptor stimulation (SNP-2 and YC1-2 groups) similarly increased arterial glucose compared to the aCSF-2 group. By contrast, infusion of L-NAME into the cNTS before carotid chemoreceptor stimulation (L-NAME-2 group) decreased arterial glucose concentration. The number of cNTS Fos-ir neurons, determined in all the groups studied except for YC1 groups, significantly increased in SNP-2 rat when compared to the aCSF-2 or SNP-2 groups. Our findings demonstrate that NO signaling, and the correlative activation of groups of cNTS neurons, plays key roles in the hyperglycemic reflex initiated by carotid chemoreceptor stimulation.
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Cuerpo Carotídeo/metabolismo , Regulación de la Expresión Génica , Hiperglucemia/metabolismo , Óxido Nítrico/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Núcleo Solitario/metabolismo , Animales , Glucemia , Arterias Carótidas/efectos de los fármacos , Arterias Carótidas/metabolismo , Células Quimiorreceptoras/metabolismo , Glucosa/metabolismo , Homeostasis , Hipoxia , Masculino , NG-Nitroarginina Metil Éster/química , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Donantes de Óxido Nítrico/química , Nitroprusiato/química , Ratas , Ratas Wistar , Transducción de Señal , Cianuro de Sodio/químicaRESUMEN
BACKGROUND: Experimental procedures will continue to be a key element while going through the learning curve in the use of the endoscope and minimally invasive procedures. We describe the technical procedure of an experimental approach to middle ear in New Zealand rabbits through external auditory canal and its relevance as an ideal model to study graft materials and serve as a training tool for potential applications in otoneurology. METHODS: A group of 28 adult New Zealand rabbits were subjected to an experimental myringoplasty, combining the transmeatal and retroauricular approach with endoscopic assistance and microsurgical technique. The different anatomical steps and systematization of the complete experimental procedure are described. RESULTS: An experimental approach to middle ear live model and basic anatomic description was successfully used, standardizing the ideal technique. The eardrum could regenerate with no complications and with functional preservation in all the myringoplasty cases. This strategy involves a safe combined approach to the tympanic membrane and others neurosurgical as transcochlear and translaberyntic approaches and is useful as a test of other experimental procedures to evaluate biomaterials to repair the eardrum currently studied. This experimental myringoplasty model also facilitates functional tests such as impedanciometry and the endoscopic follow-up of the whole process. CONCLUSIONS: The method described to perform an experimental myringoplasty (type I tympanoplasty) in a New Zealand rabbit is an option to be used as a basic model to study the behavior of the graft in the tympanic membrane. Also, basic concepts for the use of combined instrumentation are established in the treatment of eardrum lesions, as a refinement of the technical training application in microsurgery and assisted endoscopy in the transcochlear and translaberintic approaches and otoneurology areas.
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Previous work has shown that the carotid body glomus cells can function as glucose sensors. The activation of these chemoreceptors, and of its afferent nucleus in the brainstem (solitary tract nucleus - STn), induces rapid changes in blood glucose levels and brain glucose retention. Nitric oxide (NO) in STn has been suggested to play a key role in the processing of baroreceptor signaling initiated in the carotid sinus. However, the relationship between changes in NO in STn and carotid body induced glycemic changes has not been studied. Here we investigated in anesthetized rats how changes in brain glucose retention, induced by the local stimulation of carotid body chemoreceptors with sodium cyanide (NaCN), were affected by modulation of NO levels in STn. We found that NO donor sodium nitroprusside (SNP) micro-injected into STn completely blocked the brain glucose retention reflex induced by NaCN chemoreceptor stimulation. In contrast, NOS inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) increased brain glucose retention reflex compared to controls or to SNP rats. Interestingly, carotid body stimulation doubled the expression of nNOS in STn, but had no effect in iNOS. NO in STn could function to terminate brain glucose retention induced by carotid body stimulation. The work indicates that NO and STn play key roles in the regulation of brain glucose retention.
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Encéfalo/metabolismo , Cuerpo Carotídeo/efectos de los fármacos , Glucosa/metabolismo , Óxido Nítrico/farmacología , Núcleo Solitario/efectos de los fármacos , Anestesia , Animales , Cuerpo Carotídeo/metabolismo , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Donantes de Óxido Nítrico/farmacología , Óxido Nítrico Sintasa/metabolismo , Nitroprusiato/farmacología , Ratas , Ratas Wistar , Cianuro de Sodio/farmacología , Núcleo Solitario/metabolismoRESUMEN
Increasing evidence indicates that chronic exposure to environmental noise may permanently affect the central nervous system. The aim of this study was to evaluate the long-term effects of early exposure to environmental noise on the hippocampal cell proliferation of the adult male rat. Early-weaned Wistar rats were exposed for 15 days to a rats' audiogram-fitted adaptation to a noisy environment. Two months later, the rats were injected with the cellular proliferation marker 5Îbromodeoxiuridine (BrdU), and their brains were processed for immunohistochemical analysis. Coronal sections were immunolabeled with anti-BrdU antibodies to identify new-born cells in dentate gyrus (DG), cornu amonis areas CA1 and CA3. In addition, blood samples were obtained to evaluate corticosterone serum levels after noise exposure. All data are expressed as mean±standard deviation. For mean comparisons between groups, we used the Student t test. We found an increase in corticosterone serum levels after environmental noise exposure. Interestingly, noise-exposed rats showed a long-term reduction of proliferating cells in the hippocampal formation, as compared to controls. These findings indicate that chronic environmental noise exposure at young ages produces persistent non-auditory impairment that modifies cell proliferation in the hippocampal formation.
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Exposición a Riesgos Ambientales/efectos adversos , Hipocampo/fisiopatología , Ruido/efectos adversos , Animales , Antimetabolitos , Encéfalo , Bromodesoxiuridina , Proliferación Celular , Corticosterona/sangre , Inmunohistoquímica , Ratas , Ratas Wistar , Aumento de PesoRESUMEN
El hipocampo es sensible a altos niveles de glucocorticoides.Durante la respuesta de estrés, esta estructura sufre cambios bioquímicos y celulares que afectan funciones tales como la memoria espacial y la conducta exploratoria, entre otras. En este estudio analizamos la influencia del neuroesteroide progesterona (PROG) sobre los cambios inducidos por estrés en corticosterona (CORT) urinaria, memoria espacial y conducta exploratoria. Se implantó PROG o vehículo (VEHI) a ratas macho adultas castradas y se les expuso a estrés crónico por hacinamiento o ruido ultrasónico durante 10 días. Se evaluaron niveles de PROG y CORT en orina usando cromatografía líquida de alta resolución (HPLC). Los implantes de PROG inhibieron el incremento de CORT inducido por estrés, previnieron el detrimento de la memoria espacial en el laberinto acuático de Morris y eliminaron el incremento en la actividad exploratoria en la prueba del campo de agujeros. Estos resultados sugieren un efecto protector de la PROG, posiblemente mediado por los mecanismos ansiolíticos de la hormona, contra la elevación de corticoesteroides y el déficit conductual generado por las situaciones estresantes.
The hippocampus is sensitive to high levels of glucocorticoids during stress responses; it suffers biochemical and cellular changes that affect spatial memory and exploratory behavior, among others. We analyzed the influence of the neurosteroid progesterone (PROG) on stress-induced changes in urinary corticosterone (CORT) levels, spatial memory and exploratory behavior. Castrated adult male rats were implanted with PROG or vehicle (VEHI), and then exposed for ten days to chronic stress created by overcrowding or ultrasonic noise. PROG and CORT levels were assessed in urine using highperformance liquid chromatography (HPLC). Implanted PROG inhibited the rise of stress-induced CORT, prevented spatial memory impairment in the Morris water maze, and eliminated increased exploratory behavior in the hole-board test. These results suggest a protective role of PROG, possibly mediated by its anxiolytic mechanisms, against corticosteroids elevation and the behavioral deficit generated by stressful situations.
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Animales , Progesterona , Ratas/psicología , Corticosterona , Estrés PsicológicoRESUMEN
OBJECTIVE: This study investigated the cognitive effect of chronic exposure to environmental noise on RAWM performance of juvenile rats, and the ability of adult rats exposed to a novel acute stress to perform in the RAWM as a function of whether or not they were exposed to environmental noise as juveniles. METHODS: We examined the consequences of exposure to noise during the juvenile-early periadolescent period on adulthood stress response by assessing cognitive performance in the RAWM. Male rats were exposed to environmental noise during the childhood-prepubescent period (21-35 PND), and their RAWM performance was tested at the end of the exposure to noise, and then again two months later when they had to cope with a new stressful event. RAWM execution included a 3-day training phase and a reversal learning phase on day 4. Escape latency, reference memory errors and working memory errors were compared between experimental and control groups. In addition, body weight gain and serum corticosterone levels were evaluated. RESULTS: Stressed rats demonstrated spatial impairment, as evidenced by poor execution on day 4. This effect was significantly noticeable in the doubly stressed group. Noise annoyance was evidenced by reduced body weight gain and increased serum corticosterone levels. CONCLUSIONS: Our results suggest that environmental noise may produce potent stress-like effects in developing subjects that can persist into adulthood, affecting spatial learning abilities. This cognitive impairment may restrict the subject's ability to learn under a new spatial configuration.
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Aprendizaje por Laberinto/fisiología , Ruido , Aprendizaje Inverso/fisiología , Estrés Fisiológico/fisiología , Estrés Psicológico/fisiopatología , Análisis de Varianza , Animales , Peso Corporal , Masculino , Ratas , Ratas Wistar , Conducta Espacial/fisiologíaRESUMEN
Se ha descrito que el núcleo del tracto solitario (NTS), estructura del tallo cerebral y vía de relevo de las aferencias del los quimiorreceptores del senocuerpo carotídeo (RSCC), participa en el aumento en la retención de glucosa por el cerebro (RGC) ante una hipoxia. Es probable que en esta respuesta participe el óxido nítrico (NO) y la proteína Fos. En este trabajo se analiza el papel del NO en el NTS sobre la modificación de la RGC y la expresión de la proteína inmunorreactiva Fos (Fos-ir) en ratas in vivo. La inyección de un donador del NO como es el nitroprusiato de sodio (NPS) en el NTS, 4 min antes de la estimulación de los RSCC, disminuyó la RGC, pero incrementó la expresión de Fos-ir en un mayor número de neuronas en el NTS con respecto a las ratas control, que sólo recibieron líquido cefalorraquídeo artificial (LCRa) antes de la estimulación RSCC. En contraste, un inhibidor selectivo del NO como el N?-nitro-L-arginina metil éster (L-NAME) en el NTS 4 min antes de la estimulación RSCC con NaCN, aumentó la RGC, pero disminuyó el número de neuronas Fos-ir comparados con el control o con NPS. La detección inmunohistoquímica de la expresión de Fos-ir en las células del tallo cerebral indica que la estimulación RSCC activa vías dependientes de NO en el NTS, para regular la RGC. El estudio de esta población de células en el NTS, serß importante para definir su caracterización(AU)
It has been said that the nucleus tractus solitarii (NTS), one structure of the brain stem and path of apherences of chemoreceptors of carotid sinus-body, is involved in the increased glucose retention by the brain in case of hypoxia. It is likely that nitric oxide and Fos protein also take part in this response. This paper analyzes the role of nitric oxide in the NTS on the change of glucose retention by the brain and the expression of inmunoreactive protein Fos (ir-Fos) in rats in vivo. The injection of a NO donor such as sodium nitroprusiate in the NTS four minutes before the stimulation of carotid sinus-body chemoreceptors decreased glucose retention by the brain but increased the expression of ir-Fos in a higher number of neurons in NTS with respect to control group rats which only received artificial cerebrospinal fluid before the stimulation. In contrast, the use of a selective NO inhibitor such as NO-nitro-L-arginine methyl ester (L-NAME) in the NTS four minutes before the stimulation of the chemoreceptors with NaCN, increased the glucose retention by the brain but reduced the number of neurons with ir-Fos expression when compared with the control group or the sodium nitroprusiate injection. The immunohistochemical detection of ir-Fos expression in the brain stem cells indicated that stimulation of carotid sinus-body chemoreceptors activated NO-dependent paths in the NTS to regulate glucose retention by the brain. The study of this cell population in the NTS will be important to define its characterization(AU)
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Animales , Ratas , Óxido Nítrico/análisis , Glucosa , Tronco Encefálico/fisiopatología , Hipoxia/patologíaRESUMEN
Se ha descrito que el núcleo del tracto solitario (NTS), estructura del tallo cerebral y vía de relevo de las aferencias del los quimiorreceptores del senocuerpo carotídeo (RSCC), participa en el aumento en la retención de glucosa por el cerebro (RGC) ante una hipoxia. Es probable que en esta respuesta participe el óxido nítrico (NO) y la proteína Fos. En este trabajo se analiza el papel del NO en el NTS sobre la modificación de la RGC y la expresión de la proteína inmunorreactiva Fos (Fos-ir) en ratas in vivo. La inyección de un donador del NO como es el nitroprusiato de sodio (NPS) en el NTS, 4 min antes de la estimulación de los RSCC, disminuyó la RGC, pero incrementó la expresión de Fos-ir en un mayor número de neuronas en el NTS con respecto a las ratas control, que sólo recibieron líquido cefalorraquídeo artificial (LCRa) antes de la estimulación RSCC. En contraste, un inhibidor selectivo del NO como el N?-nitro-L-arginina metil éster (L-NAME) en el NTS 4 min antes de la estimulación RSCC con NaCN, aumentó la RGC, pero disminuyó el número de neuronas Fos-ir comparados con el control o con NPS. La detección inmunohistoquímica de la expresión de Fos-ir en las células del tallo cerebral indica que la estimulación RSCC activa vías dependientes de NO en el NTS, para regular la RGC. El estudio de esta población de células en el NTS, serß importante para definir su caracterización.
It has been said that the nucleus tractus solitarii (NTS), one structure of the brain stem and path of apherences of chemoreceptors of carotid sinus-body, is involved in the increased glucose retention by the brain in case of hypoxia. It is likely that nitric oxide and Fos protein also take part in this response. This paper analyzes the role of nitric oxide in the NTS on the change of glucose retention by the brain and the expression of inmunoreactive protein Fos (ir-Fos) in rats in vivo. The injection of a NO donor such as sodium nitroprusiate in the NTS four minutes before the stimulation of carotid sinus-body chemoreceptors decreased glucose retention by the brain but increased the expression of ir-Fos in a higher number of neurons in NTS with respect to control group rats which only received artificial cerebrospinal fluid before the stimulation. In contrast, the use of a selective NO inhibitor such as NO-nitro-L-arginine methyl ester (L-NAME) in the NTS four minutes before the stimulation of the chemoreceptors with NaCN, increased the glucose retention by the brain but reduced the number of neurons with ir-Fos expression when compared with the control group or the sodium nitroprusiate injection. The immunohistochemical detection of ir-Fos expression in the brain stem cells indicated that stimulation of carotid sinus-body chemoreceptors activated NO-dependent paths in the NTS to regulate glucose retention by the brain. The study of this cell population in the NTS will be important to define its characterization.
Asunto(s)
Animales , Ratas , Hipoxia/patología , Glucosa , Óxido Nítrico/análisis , Tronco Encefálico/fisiopatologíaRESUMEN
We have previously reported that dietary tryptophan (TRP) restriction in a rat crucial postnatal developmental stage induces depression-like behavior and alters dendritic spine density in CA1 pyramidal neurons and granule cells of the hippocampus. Due to astrocyte involvement in critical brain mechanisms, it seems worth to investigate possible adaptive changes in the glial population with TRP restriction. Experimental rats were fed with low TRP diet (20% of TRP level of the laboratory rat chow) from postnatal days 30-60. Antibody against glial fibrillary acidic protein (GFAP), a principal intermediate filament in astrocytes, was used to evaluate cytoskeletal hypertrophy and glial proliferation. Our results showed an increase in size and branching of GFAP-immunoreactive (IR) cells in the dorsal hippocampus and amygdala, characteristics of an astrocytic activation. No significant differences were found regarding the number of GFAP-IR cells in both regions. These results indicate that dietary TRP restriction can induce astrocytic activation, hence, provide further evidences supporting the hypothesis that serotonin may also modulate glial morphology.
Asunto(s)
Astrocitos/patología , Encéfalo/patología , Citoesqueleto/patología , Alimentos Formulados/efectos adversos , Desnutrición/patología , Triptófano/deficiencia , Amígdala del Cerebelo/metabolismo , Amígdala del Cerebelo/patología , Amígdala del Cerebelo/fisiopatología , Animales , Astrocitos/metabolismo , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatología , Forma de la Célula/fisiología , Citoesqueleto/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Gliosis/metabolismo , Gliosis/patología , Gliosis/fisiopatología , Hipocampo/metabolismo , Hipocampo/patología , Hipocampo/fisiopatología , Hipertrofia/metabolismo , Hipertrofia/patología , Hipertrofia/fisiopatología , Masculino , Desnutrición/metabolismo , Desnutrición/fisiopatología , Ratas , Ratas Wistar , Serotonina/biosíntesis , Serotonina/deficienciaRESUMEN
Mediante el análisis químico proximal se determinaron proteínas (PC), grasas (GC), fibras (FC), cenizas, humedad y extracto libre de nitrógeno (ELN) de las semillas de Enterolobium cyclocarpum, y con espectrofotometría se determinaron sus factores antinutricionales. Por el contenido de minerales, carbohidratos y proteínas que posee esta leguminosa, tiene potencial industrial, medicinal y químico, siendo una limitante la presencia de factores antinutricionales tales como glucósidos cianogénicos e inhibidores de tripsina. Mediante hidrólisis enzimática (ß-glucosidasa) se analizó la inhibición de tripsina de un extracto acuoso (NaOH 0,1N) de la muestra y en una solución estándar de tripsina se midió la actividad proteolítica en un sustrato sintético (benzoil-arginina-p-nitroanilida). En las semillas completas se encontró PC 26,13%, GC 2,85%, FC 4,95%, cenizas 2,95% y ELN 63,1%. En las almendras desecadas los valores fueron PC 34,5%, GC 7,6%, ausencia de FC, cenizas 3,3% y ELN 54,6%. Se encontraron 4,82 unidades de inhibidores de tripsina/mg, ausencia de hemaglutininas y 0,76mg de ácido cianhídrico en 100g de semillas. Estos valores correspondientes a los factores antinutricionales descritos no constituyen un riesgo al consumir las semillas, ya que son termolábiles y se eliminan por cocción en agua.
Chemical analyses were performed to quantify the protein (CP), fat (CF), fiber (CF), ash, humidity, nitrogen free extract (NFE) and antinutritional factors in extracts from Enterolobium cyclocarpum seeds. E. cyclocarpum seeds have a great potential in pharmaceutical and chemical industries due to the high content of minerals, carbohydrates and proteins. However, the seeds also contain cyanogenic glycosides such as trypsin inhibitory factor and cyanhidric acid, resulting in antinutritional effects. Trough enzymatic hydrolysis (ß-glycosidase), trypsine inhibition on an aqueous extract of the sample (0.1 N NaOH). By using a standard trypsine solution, the proteolytic activity in a synthetic substrate (benzoyl-arginine-p-nitroanilide) was studied. Analyses of the complete seeds showed; CP 26.13%, CF 2.85%, CF 4.95%, Ash 2.95%, and NFE 63.1%. The dried almonds contained CP 34.5%, CF 7.6%, undetectable fiber, ash 3.3%, and NFE 54.6%. No hemaglutinins were detected, whereas 4.82 units/mg of trypsine inhibition and 0.76 mg/100g of HCN were found. The low concentrations of trypsine inhibitor and HCN will be reduced even more by the heat treatment previous consumption, which makes the seeds suitable for human beings or animals.
Mediante a análise química proximal se determinaram proteínas (PC), gorduras (GC), fibras (FC), cinzas, umidade e extrato livre de nitrogênio (ELN) das sementes de Enterolobium cyclocarpum, e com espectrofotometria se determinaram seus fatores antinutricionais. Pelo conteúdo de minerais, carboidratos e proteínas que possui, esta leguminosa têm potencial industrial, medicinal e químico, sendo uma limitante a presença de fatores antinutricionais tais como glicosídeos cianogênicos e inibidores de tripsina. Mediante hidrólise enzimática (ß-glucosidase) se analisou a inibição de tripsina de um extrato aquoso (NaOH 0,1N) da amostra e em uma solução padrão de tripsina se mediu a atividade proteolítica em um substrato sintético (benzoil-arginina-p-nitroanilida). Nas sementes completas se encontrou PC 26,13%, GC 2,85%, FC 4,95%, cinzas 2,95% e ELN 63,1%. Nas amêndoas dissecadas os valores foram PC 34,5%, GC 7,6%, ausência de FC, cinzas 3,3% e ELN 54.6%. Encontraram-se 4,82 unidades de inibidores de tripsina/mg, ausência de hemaglutininas e 0,76mg de ácido cianídrico em 100g de sementes. Estes valores correspondentes aos fatores antinutricionais descritos não constituem um risco ao consumir as sementes, já que são termolábeis e se eliminam por cozimento em água.
RESUMEN
Deflazacort (DFZ) is a synthetic glucocorticoid that has few adverse effects on glucose and calcium metabolism and fewer deleterious effects on the neuronal population. Therefore, it may have a crucial role in the treatment of patients with autoimmune disorders associated with central nervous system or metabolic affectations. To date, the pharmacologic safety profile of DFZ is considered similar to that of other glucocorticoids. Nevertheless, cumulative clinical and laboratory evidence suggests that DFZ has, in fact, greater immunosuppressive activity than was previously thought. Therefore, it is possible that DFZ increases the risk of acquiring opportunistic infection compared with other synthetic glucocorticoids. Additional pharmacologic studies are needed to fully establish the immunosuppressive potency of DFZ and, consequently, to determine the appropriate ratio of bioequivalence in humans.