Navegando por Palavras-chave "brain"

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    Aerobic exercise reduces hippocampal ERK and p38 activation and improves memory of middle-aged rats
    (Wiley, 2017) Cardoso, Fabrizio dos Santos; Franca, Erivelton Fernandes; Serra, Fernando Tadeu; Victorino, Angelica Begatti [UNIFESP]; de Almeida, Alexandre Aparecido [UNIFESP]; Fernandes, Jansen [UNIFESP]; Cabral, Francisco Romero; Venancio, Daniel Paulino; Arida, Ricardo Mario [UNIFESP]; da Silva, Sergio Gomes
    Aging is often accompanied by cognitive decline, memory impairment, and an increased susceptibility to neurodegenerative disorders. Although the physiological processes of aging are not fully understood, these age-related changes have been interpreted by means of various cellular and molecular theories. Among these theories, alterations in the intracellular signaling pathways associated with cell growth, proliferation, and survival have been highlighted. Based on these observations and on recent evidence showing the beneficial effects of exercise on cognitive function in the elderly, we investigated the cell signaling pathways in the hippocampal formation of middle-aged rats (18months old) submitted to treadmill exercise over 10 days. To do this, we evaluated the hippocampal activation of intracellular signaling proteins linked to cell growth, proliferation, and survival, such as Akt, mTOR, p70S6K, ERK, CREB, and p38. We also explored the cognitive performance (inhibitory avoidance) of middle-aged rats. It was found that physical exercise reduces ERK and p38 activation in the hippocampal formation of aged rats, when compared to the control group. The hippocampal activation and expression of Akt, mTOR, p70S6K, and CREB were not statistically different between the groups. It was also observed that aged rats from the exercise group exhibited better cognitive performance in the inhibitory avoidance task (aversive memory) than aged rats from the control group. Our results indicate that physical exercise reduces intracellular signaling pathways linked to inflammation and cell death (i.e., ERK and p38) and improves memory in middle-aged rats.
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    Assessment of factors that confound MRI and neuropathological correlation of human postmortem brain tissue
    (Springer, 2008-09-01) Grinberg, Lea T.; Amaro, Edson; Teipel, Stefan; Santos, Denis Dionizio dos; Pasqualucci, Carlos Augusto; Leite, Renata E. P.; Camargo, Celia Regina; Goncalves, Jaqueline Alba; Sanches, Ariadne Goncalves [UNIFESP]; Santana, Miriam; Ferretti, Renata E. L.; Jacob-Filho, Wilson; Nitrini, Ricardo; Heinsen, Helmut; Brazilian Aging Brain Study Grp; Univ Wurzburg; Universidade de São Paulo (USP); Inst Israelita Ensino & Pesquisa Albert Einstein; Univ Rostock; Universidade Federal de São Paulo (UNIFESP)
    In spite of considerable technical advance in MRI techniques, the optical resolution of these methods are still limited. Consequently, the delineation of cytoarchitectonic fields based on probabilistic maps and brain volume changes, as well as small-scale changes seen in MRI scans need to be verified by neuronanatomical/neuropathological diagnostic tools. To attend the current interdisciplinary needs of the scientific community, brain banks have to broaden their scope in order to provide high quality tissue suitable for neuroimaging- neuropathology/anatomy correlation studies. the Brain Bank of the Brazilian Aging Brain Research Group (BBBABSG) of the University of São Paulo Medical School (USPMS) collaborates with researchers interested in neuroimaging-neuropathological correlation studies providing brains submitted to postmortem MRI in-situ. in this paper we describe and discuss the parameters established by the BBBABSG to select and to handle brains for fine-scale neuroimaging-neuropathological correlation studies, and to exclude inappropriate/unsuitable autopsy brains. We tried to assess the impact of the postmortem time and storage of the corpse on the quality of the MRI scans and to establish fixation protocols that are the most appropriate to these correlation studies. After investigation of a total of 36 brains, postmortem interval and low body temperature proved to be the main factors determining the quality of routine MRI protocols. Perfusion fixation of the brains after autopsy by mannitol 20% followed by formalin 20% was the best method for preserving the original brain shape and volume, and for allowing further routine and immunohistochemical staining. Taken to together, these parameters offer a methodological progress in screening and processing of human postmortem tissue in order to guarantee high quality material for unbiased correlation studies and to avoid expenditures by post-imaging analyses and histological processing of brain tissue.
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    Chronic imipramine treatment-induced changes in acetylcholinesterase (EC 3.1.1.7) activity in discrete rat brain regions
    (Associação Brasileira de Divulgação Científica, 1997-08-01) Camarini, Rosana [UNIFESP]; Venditti, Marco Antonio Campana [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Cholinergic as well as monoaminergic neurotransmission seems to be involved in the etiology of affective disorders. Chronic treatment with imipramine, a classical antidepressant drug, induces adaptive changes in monoaminergic neurotransmission. In order to identify possible changes in cholinergic neurotransmission we measured total, membrane-bound and soluble acetylcholinesterase (Achase) activity in several rat brain regions after chronic imipramine treatment. Changes in Achase activity would indicate alterations in acetylcholine (Ach) availability to bind to its receptors in the synaptic cleft. Male rats were treated with imipramine (20 mg/kg, ip) for 21 days, once a day. Twenty-four hours after the last dose the rats were sacrificed and homogenates from several brain regions were prepared. Membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) after chronic imipramine treatment was significantly decreased in the hippocampus (control = 188.8 ± 19.4, imipramine = 154.4 ± 7.5, P<0.005) and striatum (control = 850.9 ± 59.6, imipramine = 742.5 ± 34.7, P<0.005). A small increase in total Achase activity was observed in the medulla oblongata and pons. No changes in enzyme activity were detected in the thalamus or total cerebral cortex. Since the levels of Achase seem to be enhanced through the interaction between Ach and its receptors, a decrease in Achase activity may indicate decreased Ach release by the nerve endings. Therefore, our data indicate that cholinergic neurotransmission is decreased after chronic imipramine treatment which is consistent with the idea of an interaction between monoaminergic and cholinergic neurotransmission in the antidepressant effect of imipramine
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    Comparative analysis of MR sequences to detect structural brain lesions in tuberous sclerosis
    (Springer, 2006-02-01) Gama, HPP; Rocha, A. J. da; Braga, F. T.; Silva, C. J. da; Maia, ACM; Meirelles, RGD; Rego, JIM do; Lederman, H. M.; Santa Casa Misericordia São Paulo; Universidade Federal de São Paulo (UNIFESP)
    Background: Tuberous sclerosis (TS) is a neurocutaneous genetically inherited disease with variable penetrance characterized by dysplasias and hamartomas affecting multiple organs. MR is the imaging method of choice to demonstrate structural brain lesions in TS. Objective: To compare MR sequences and determine which is most useful for the demonstration of each type of brain lesion in TS patients. Materials and methods: We reviewed MR scans of 18 TS patients for the presence of cortical tubers, white matter lesions (radial bands), subependymal nodules, and subependymal giant cell astrocytoma (SGCA) on the following sequences: (1) T1-weighted spin-echo (T1 SE) images before and after gadolinium (Gd) injection; (2) nonenhanced T1 SE sequence with an additional magnetization transfer contrast medium pulse on resonance (T1 SE/MTC); and (3) fluid-attenuated inversion recovery (FLAIR) sequence. Results: Cortical tubers were found in significantly (P < 0.05) larger numbers and more conspicuously in FLAIR and T1 SE/MTC sequences. the T1 SE/MTC sequence was far superior to other methods in detecting white matter lesions (P < 0.01). There was no significant difference between the T1 SE/MTC and T1 SE (before and after Gd injection) sequences in the detection of subependymal nodules; FLAIR sequence showed less sensitivity than the others in identifying the nodules. T1 SE sequences after Gd injection demonstrated better the limits of the SGCA. Conclusion: We demonstrated the importance of appropriate MRI sequences for diagnosis of the most frequent brain lesions in TS. Our study reinforces the fact that each sequence has a particular application according to the type of TS lesion. Gd injection might be useful in detecting SGCA; however, the parameters of size and location are also important for a presumptive diagnosis of these tumors.
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    Content of liver and brain ubiquinol-9 and ubiquinol-10 after chronic ethanol intake in rats subjected to two levels of dietary alpha-tocopherol
    (Harwood Acad Publ Gmbh, 2000-01-01) Junqueira, VBC; Carrasquedo, F.; Azzalis, L. A.; Giavarotti, KAS; Giavarotti, L.; Rodrigues, L.; Fraga, C. G.; Boveris, A.; Videla, L. A.; Universidade Federal de São Paulo (UNIFESP); Univ Buenos Aires; Universidade de São Paulo (USP); Univ Chile
    To assess the effect of chronic ethanol ingestion in the content of the reduced forms of coenzymes Q(9) (ubiquinol-9) and Q(10) (ubiquinol-10) as a factor contributing to oxidative stress in liver and brain, male Wistar rats were fed ad libitum a basal diet containing either 10 or 2.5 mg alpha-tocopherol/100% diet (controls), or the same basal diet plus a 32% ethanol-25% sucrose solution. After three months treatment, ethanol chronically-treated rats showed identical growth rates to the isocalorically pair-fed controls, irrespectively of alpha-tocopherol dietary level. Lowering dietary alpha-tocopherol led to a decreased content of this vitamin in the liver and brain of control rats, without changes in that of ubiquinol-9, and increased levels of hepatic ubiquinol-10 and total glutathione (tGSH), accompanied by a decrease in brain tGSH. At the two levels of dietary alpha-tocopherol, ethanol treatment significantly decreased the content of hepatic alpha-tocopherol and ubiquinols 9 and 10. This effect was significantly greater at 10 mg alpha-tocopherol/100% diet than at 2.5, whereas those of tGSH were significantly elevated by 43% and 9%, respectively. Chronic ethanol intake did not alter the content of brain alpha-tocopherol and tGSH, whereas those of ubiquinol-9 were significantly lowered by 20% and 14% in rats subjected to 10 and 2.5 mg alpha-tocopherol/100 g diet, respectively. It is concluded that chronic ethanol intake at two levels of dietary alpha-tocopherol induces a depletion of hepatic alpha-tocopherol and ubiquinols 9 and 10, thus contributing to ethanol-induced oxidative stress in the liver tissue. This effect of ethanol is dependent upon the dietary level of alpha-tocopherol, involves a compensatory enhancement in hepatic tGSH availability, and is not observed in the brain tissue, probably due to its limited capacity for ethanol biotransformation and glutathione synthesis.
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    Differential effects of exercise on brain opioid receptor binding and activation in rats
    (Wiley-Blackwell, 2015-01-01) Arida, Ricardo Mario [UNIFESP]; Silva, Sergio Gomes da [UNIFESP]; Almeida, Alexandre Aparecido de [UNIFESP]; Cavlheiro, Esper Abrao [UNIFESP]; Zavala-Tecuapetla, Cecilia; Brand, Serge; Rocha, Luisa; Universidade Federal de São Paulo (UNIFESP); Hosp Israelita Albert Einstein; Ctr Res & Adv Studies; Univ Basel
    Physical exercise stimulates the release of endogenous opioid peptides supposed to be responsible for changes in mood, anxiety, and performance. Exercise alters sensitivity to these effects that modify the efficacy at the opioid receptor. Although there is evidence that relates exercise to neuropeptide expression in the brain, the effects of exercise on opioid receptor binding and signal transduction mechanisms downstream of these receptors have not been explored. Here, we characterized the binding and G protein activation of mu opioid receptor, kappa opioid receptor or delta opioid receptor in several brain regions following acute (7 days) and chronic (30 days) exercise. As regards short-(acute) or longterm effects (chronic) of exercise, overall, higher opioid receptor binding was observed in acute-exercise animals and the opposite was found in the chronic-exercise animals. the binding of [S-35]GTP gamma S under basal conditions (absence of agonists) was elevated in sensorimotor cortex and hippocampus, an effect more evident after chronic exercise. Divergence of findings was observed for mu opioid receptor, kappa opioid receptor, and delta opioid receptor receptor activation in our study. Our results support existing evidence of opioid receptor binding and G protein activation occurring differentially in brain regions in response to diverse exercise stimuli.
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    Ditterential effects of spontaneous versus forced exercise in rats on the staining of parvalbumin-positive neurons in the hippocampal formation
    (Elsevier B.V., 2004-07-08) Arida, R. M.; Scorza, C. A.; Silva, A. V. da; Scorza, F. A.; Cavalheiro, E. A.; Universidade Federal de São Paulo (UNIFESP); UMC
    To investigate whether the type of physical activity, voluntary or forced, would promote different morphological changes in hippocampal formation we performed an immunocytochemical study using the parvalbumin (PV) distribution as a marker. Animals submitted to the voluntary exercise were placed in a voluntary wheel running and those submitted to the forced exercise were placed in a motor driven treadmill. Both exercise groups were submitted to 10 consecutive days of physical activity. It was observed a higher number of PV-positive cells in the hilus of dentate gyrus (DG) in the voluntary and forced exercise groups when compared to the control group. the voluntary exercise group also presented a stronger fiber staining in the DG hilus than the forced exercise and control groups. in contrast, no differences were found in the pattern of PV staining in CA1/CA3 region between exercise and control groups. These findings demonstrate that physical activity leads to prominent plastic changes in the hippocampal formation of rats that were more evident following voluntary activity. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
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    Early exercise promotes positive hippocampal plasticity and improves spatial memory in the adult life of rats
    (Wiley-Blackwell, 2012-02-01) Silva, Sergio Gomes da [UNIFESP]; Unsain, Nicolas; Hugo Masco, Daniel; Toscano-Silva, Michelle [UNIFESP]; Amorim, Henrique Alves de [UNIFESP]; Silva Araujo, Bruno Henrique [UNIFESP]; Rodrigues Simoes, Priscila Santos [UNIFESP]; Naffah-Mazzacoratti, Maria da Graca [UNIFESP]; Mortara, Renato Arruda [UNIFESP]; Scorza, Fulvio Alexandre [UNIFESP]; Cavalheiro, Esper Abrao [UNIFESP]; Arida, Ricardo Mario [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Nacl Cordoba
    There is a great deal of evidence showing the capacity of physical exercise to enhance cognitive function, reduce anxiety and depression, and protect the brain against neurodegenerative disorders. Although the effects of exercise are well documented in the mature brain, the influence of exercise in the developing brain has been poorly explored. Therefore, we investigated the morphological and functional hippocampal changes in adult rats submitted to daily treadmill exercise during the adolescent period. Male Wistar rats aged 21 postnatal days old (P21) were divided into two groups: exercise and control. Animals in the exercise group were submitted to daily exercise on the treadmill between P21 and P60. Running time and speed gradually increased over this period, reaching a maximum of 18 m/min for 60 min. After the aerobic exercise program (P60), histological and behavioral (water maze) analyses were performed. the results show that early-life exercise increased mossy fibers density and hippocampal expression of brain-derived neurotrophic factor and its receptor tropomyosin-related kinase B, improved spatial learning and memory, and enhanced capacity to evoke spatial memories in later stages (when measured at P96). It is important to point out that while physical exercise induces hippocampal plasticity, degenerative effects could appear in undue conditions of physical or psychological stress. in this regard, we also showed that the exercise protocol used here did not induce inflammatory response and degenerating neurons in the hippocampal formation of developing rats. Our findings demonstrate that physical exercise during postnatal development results in positive changes for the hippocampal formation, both in structure and function. (C) 2010 Wiley Periodicals, Inc.
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    Effects of acute AV3V lesions on renal and hindlimb vasodilation induced by volume expansion
    (Lippincott Williams & Wilkins, 1999-10-01) Colombari, Debora Simões de Almeida [UNIFESP]; Cravo, Sergio Luiz [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The role of the anteroventral third ventricle (AV3V) region in the cardiovascular adjustments to volume expansion (VE) with 4% Ficoll (1% body weight, 1.4 mL/min) was studied in urethane-anesthetized rats. In sham-lesioned animals, VE produced a transitory (less than or equal to 20 minutes) increase in mean arterial pressure, which peaked at 10 minutes (10+/-3 mm Hg), and sustained increases of renal (123+/-10% and 127+/-6% of baseline, respectively, 10 and 40 minutes after VE) and hindlimb vascular (157+/-19% and 153+/-9% of baseline) conductance. After AV3V lesions, VE induced a sustained increase in mean arterial pressure. Although renal blood flow increased in response to VE, renal vascular conductance was unaffected, indicating that renal vasodilation was abolished. On the other hand, after AV3V lesions, the increases in hindlimb blood flow and vascular conductance were higher than those observed in sham-lesioned rats. Results obtained demonstrated that the AV3V region is essential for the renal vasodilation induced by VE.
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    Effects of regular cannabis use on neurocognition, brain structure, and function: a systematic review of findings in adults
    (Taylor & Francis Inc, 2018) Nader, Danilo A. [UNIFESP]; Sanchez, Zila M. [UNIFESP]
    Background: Cannabis is the most used illicit drug worldwide. The long-standing consequences for the central nervous system associated with frequent cannabis use have not been well delineated and should be determined. Objective: To review recent studies on the effects of regular cannabis use regarding its effects on cognition, brain structure, and function in adults. Methods: A systematic literature review was conducted by performing electronic searches in the PubMed, LILACS, and SciELO databases (2010-2016). The initial search identified 898 records. They were evaluated for relevance according to the inclusion and exclusion criteria and 56 studies were included. Results: The neuropsychological studies provide evidence for subtle cognitive deficits at least 7 days after heavy cannabis use. The structural neuroimaging studies show growing evidence of abnormalities in hippocampus volume and gray matter density of cannabis users relative to controls
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    Encephalometry on the medial face of the human brain hemisphere: a necropsy study
    (Academia Brasileira de Neurologia - ABNEURO, 2005-06-01) Ribeiro, Paula J. [UNIFESP]; Cricenti, Serafim Vicenzo [UNIFESP]; Lancellotti, Carmen Lucia Penteado; Universidade Federal de São Paulo (UNIFESP); SCSP FCM Departamento de Patologia
    This study aims to evaluate the dimensions of the human brain, specifically in the frontal cortex, helping the analysis of neuroimaging. A form was made to register and describe encephalic measurements and 81 cerebral hemispheres (CH) were analyzed. Male individuals showed larger CH length; wider superior frontal gyrus in the right CH; bigger encephalic weight and corpus callosum (CC) width. The proportion of measurement from the frontal pole to the most anterior part of the CC genu, related to the CH length gets smaller with aging, whereas the average distance from the most posterior part of the splenum of the CC to the occipital pole was bigger in both male CHs and there was a tendency of decrease in this difference with aging.
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    Ethanol intake during lactation impairs milk production in rats and affects growth and metabolism of suckling pups
    (Elsevier B.V., 1999-05-01) Do Carmo, MGT; Do Nascimento, CMO; Martin, A.; Herrera, E.; Universidade Federal do Rio de Janeiro (UFRJ); Universidade Federal de São Paulo (UNIFESP); Hosp Ramon y Cajal; Univ San Pablo
    From parturition, lactating Wistar rats were given 20% alcohol in drinking water and fed a solid diet ad lib (group AL). Pair-fed (PF) and control (C) rats were fed solid diet and given water ad lib (C). All animals were sacrificed on the 12th day of lactation. Ethanol treatment decreased food intake and milk production in lactating rats to a greater level than in PF rats, and a greater reduction in body weight of the AL pups was noted. Brain weight, protein concentration, and DNA content were also lower in pups of AL dams than of PF dams, whereas liver glycogen concentration was higher in the former. Pups from AL dams had higher circulating levels of beta-OH-butyrate, triglyceride, and free fatty acids than those from either C or PF dams. Plasma glucose concentration was lower in both PF and AL than in C pups, whereas the AL group had lower plasma protein concentration than any of the other groups. We conclude that maternal alcohol intake during lactation greatly impairs milk production, and although the known increase of lipid content in milk in rats studied under similar conditions allows an enhanced lipidic components in the pups, this adaptation does not allow normal growth and brain development. (C) 1999 Elsevier Science Inc. All rights reserved.
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    Excitatory effects of nitric oxide within the rostral ventrolateral medulla of freely moving rats
    (Amer Heart Assoc, 1997-09-01) Pinge, Marli Cardoso Martins [UNIFESP]; Passy, Izabel Baraldi [UNIFESP]; Lopes, Oswaldo Ubriaco [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The aim of the present study was to examine the participation of NO in the rostral ventrolateral medulla (RVLM) of freely moving rats. We utilized NO donors and L-arginine, which were microinjected into the RVLM. Unilateral microinjection (100 nL) of 2.5 nmol sodium nitroprusside produced a biphasic response consisting of an initial, rapid increase in arterial pressure (AP) from 125+/-5 to 161+/-8 mm Hg (P<.01) and a second, long-lasting response with a progressive increase in AP (maximum Delta peak, 34+/-9 mm Hg; P<.01). Another NO donor, S-nitroso-N-acetylpenicillamine (SNAP; 2.5 nmol), also produced immediate hypertension from 118+/-5 mm Hg to 168+/-7 mm Hg (P<.01) but without the second, long-lasting response. L-Arginine (5, 24, and 140 nmol) produced a gradual increase in AP. L-Glutamate (5 nmol) microinjected into the RVLM produced an increase in AP from 122+/-9 mm Hg to 171+/-8 mm Hg (P<.01) and bradycardia from 342+/-10 to 315+/-8 beats/min. This AP response was significantly attenuated, from 115+/-7 to 128+/-9 mm Hg (P<.05), after microinjection of methylene blue (3 nmol) without alterations In heart rate. These results indicate that NO may have an excitatory effect on the RVLM of freely moving rats, probably in association with glutamatergic synapses via cGMP mechanisms.
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    Hemorrhagic cerebral metastasis as a first manifestation of a hepatocellular carcinoma: case report
    (Academia Brasileira de Neurologia - ABNEURO, 1998-09-01) Peres, Mario Fernando Prieto [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; Malheiros, Suzana Maria Fleury [UNIFESP]; Ferraz, Henrique Ballalai [UNIFESP]; Stávale, João Norberto [UNIFESP]; Gabbai, Alberto Alain [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    We report herein a rare instance in which a patient presented with a hemorrhagic cerebral metastasis as the initial manifestation of a hepatocellular carcinoma (HCC). A few cases of cerebral metastasis from HCC have been reported in the literature, mainly from eastern countries. This is the first report from South America of a cerebral metastasis from hepatocellular carcinoma.
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    Increased basal plasma brain-derived neurotrophic factor levels in sprint runners
    (Springer, 2011-10-01) Correia, Paulo Roberto [UNIFESP]; Scorza, Fulvio Alexandre [UNIFESP]; Silva, Sergio Gomes da [UNIFESP]; Pansani, Aline [UNIFESP]; Toscano-Silva, Michelle [UNIFESP]; Almeida, Antonio Carlos de; Arida, Ricardo Mario [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Fed Sao Joao del Rei
    Objective Exercise is known to enhance circulating brain-derived neurotrophic factor (BDNF) levels in healthy humans. BDNF changes have been measured in endurance but not in strength exercise. the present study aimed to investigate whether anaerobic activity such as sprinting differentially alters basal plasma BDNF concentration. Methods Brazilian sprinters (100 m) at either the international (Olympics and Outdoor World Championships) (n = 14) or the domestic level (n = 8), and sedentary subjects (n = 15), were recruited. Plasma BDNF concentrations were analyzed by enzyme-linked immunosorbent assay. Results the basal plasma BDNF concentrations were significantly higher in the international and the domestic sprinters than in the sedentary subjects. in addition, sprinters at the international level had higher plasma BDNF concentrations than those at the domestic level. Conclusion Our findings suggest that increased basal plasma BDNF level is related to enhanced exercise performance.
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    Kidney-Induced Hypertension Depends on Superoxide Signaling in the Rostral Ventrolateral Medulla
    (Lippincott Williams & Wilkins, 2010-08-01) Oliveira-Sales, Elizabeth Barbosa de [UNIFESP]; Colombari, Debora Simões de Almeida; Davisson, Robin L.; Kasparov, Sergey; Hirata, Aparecida Emiko [UNIFESP]; Campos, Ruy Ribeiro [UNIFESP]; Paton, Julian Francis Richmond; Univ Bristol; Universidade Federal de São Paulo (UNIFESP); Univ Estadual Paulista; Cornell Univ; Weill Cornell Med Coll
    Reactive oxygen species in peripheral cardiovascular tissues are implicated in the pathogenesis of 2 kidney-1 clip hypertension. We recently identified an imbalance between reactive oxygen species generation and oxidant scavenging in the rostral ventrolateral medulla (RVLM) of 2 kidney-1 clip in rats. We tested whether enhanced superoxide signaling in RVLM of 2 kidney-1 clip rats contributes to the chronic hypertension via sympathetic activation in conscious rats. We enhanced superoxide scavenging in RVLM by overexpressing cytoplasmically targeted superoxide dismutase using an adenoviral vector (Ad-CMV-CuZnSOD) in Wistar rats (male, 150 to 180 g) in which the left renal artery was occluded partially 3 weeks earlier. Hypertension was documented using radiotelemetry recording of arterial pressure in conscious rats for 6 weeks. Renovascular hypertension elevated both serine phosphorylation of p47phox subunit of NADPH and superoxide levels in RVLM. the elevated superoxide levels were normalized by expression of CuZnSOD in RVLM. Moreover, the hypertension produced in the 2 kidney-1 clip rats was reversed 1 week after viral-mediated expression of CuZnSOD. This antihypertensive effect was maintained and associated with a decrease in the low-frequency spectra of systolic blood pressure variability, suggesting reduced sympathetic vasomotor tone. the expression of CuZnSOD was localized to RVLM neurons, of which some contained tyrosine hydroxylase. None of the above variables changed in control rats receiving Ad-CMV-eGFP in RVLM. in Goldblatt hypertension, superoxide signaling in the RVLM plays a major role in the generation of sympathetic vasomotor tone and the chronic sustained hypertension in this animal model. (Hypertension. 2010;56:290-296.)
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    Neural correlates of the LSD experience revealed by multimodal neuroimaging
    (Natl Acad Sciences, 2016) Carhart-Harris, Robin L.; Muthukumaraswamy, Suresh; Roseman, Leor; Kaelen, Mendel; Droog, Wouter; Murphy, Kevin; Tagliazucchi, Enzo; Schenberg, Eduardo Ekman [UNIFESP]; Nest, Timothy; Orban, Csaba; Leech, Robert; Williams, Luke T.; Williams, Tim M.; Bolstridge, Mark; Sessa, Ben; McGonigle, John; Sereno, Martin I.; Nichols, David; Hellyer, Peter J.; Hobden, Peter; Evans, John; Singh, Krish D.; Wise, Richard G.; Curran, H. Valerie; Feilding, Amanda; Nutt, David J.
    Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD's marked effects on the visual cortex did not significantly correlate with the drug's other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of "ego-dissolution" and "altered meaning," implying the importance of this particular circuit for the maintenance of "self" or "ego" and its processing of "meaning." Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.
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    Nitric oxide-dependent guanylyl cyclase participates in the glutamatergic neurotransmission within the rostral ventrolateral medulla of awake rats
    (Lippincott Williams & Wilkins, 1999-10-01) Pinge, Marli Cardoso Martins [UNIFESP]; Araujo, G. C.; Lopes, Oswaldo Ubriaco [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    A well-known action of nitric oxide (NO) is to stimulate the soluble form of guanylyl cyclase, evoking an accumulation of cyclic GMP in target cells. The aim of the present study was to examine the effects of inhibition of guanylyl cyclase dependent on NO during cardiovascular responses induced by L-glutamate and S-nitrosoglutathione (SNOG) microinjected into the rostral ventrolateral medulla (RVLM) of awake rats. Three days before the experiments, adult male Wistar rats (280 to 320 g) were anesthetized for implantation of guide cannulas to the desired stereotaxic position (AP=-2.5 mm, L=1.8 mm) in relation to lambda. The cannulas were fixed to the skull with acrylic cement. Twenty-four hours before the experiments, a femoral artery and vein were cannulated for recording arterial pressure (AP) and heart rate (HR) and injection of anesthetic. Unilateral microinjections (100 nL) of L-glutamate (5 nmol/L) and SNOG (2.5 nmol/L) were made into the histologically confirmed RVLM. The cardiovascular responses to these drugs were evaluated before and after microinjection (3 nmol/L, 200 nL) of either methylene blue or oxodiazoloquinoxaline (ODQ). The hypertensive effect of L-glutamate was attenuated by 74% after methylene blue (Delta A=49+/-8 to 13+/-4 mm Hg) and by 80.5% after ODQ (Delta AP=30+/-2 to 6+/-2 mm HS) The increase in AP produced by SNOG was fully blocked by ODQ (Delta AP=39+/-8 to 1+/-2 mm Hg). These data indicate that cyclic GMP mechanisms have a key role in glutamatergic neurotransmission in the RVLM of awake rats, and it is most probable that NO participates: in this response.
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    Physical training in developing rats does not influence the kindling development in the adult life
    (Elsevier B.V., 2007-03-16) Arida, Ricardo Mario; Scorza, Fulvio Alexandre; Silva de Lacerda, Aline Fabiana; Silva, Sergio Gomes da; Cavalheiro, Esper Abrao; Universidade Federal de São Paulo (UNIFESP); Univ Mogi das Cruzes
    The positive effect of physical exercise programs on seizure frequency and severity has been demonstrated both in adult human and animals. However, this investigation during animal brain development has not been examined. To this purpose, the present work was aimed to analyse the effect of physical exercise training in rats after weaning on the kindling process in the adulthood. Thirty rats were divided into 3 groups: the first group (EX=10) was submitted to daily bout of aerobic exercise (60 min running on the treadmill at 24/26 m/min) between P21 and 60 days of age. After this period of training, animals were submitted to 60 min running at the same speed and kindling stimulated one min post-exercise. the second group (SHAM=10) was maintained in the treadmill for the same time as the trained group without being submitted to physical exercise. the third group served as control (CTL=10). the number of stimulations required to reach stage 5 for the EX group was not statistically different from CTL and SHAM groups. However, the EX group spent a longer time and a shorter afterdischarge (AD) in stage I compared to the CTL and SHAM groups. the number of stimulations and AD duration in stage 2, 3 and 4 was not statistically different between all the groups. Taken together, our study showed that although forced physical exercise in developing rats does not exert significant influence to reach the stage 5 of amygdala kindling in the adult life its interference during the process of epileptogenesis indicate a positive effect of exercise in developing brain. (c) 2006 Elsevier Inc. All rights reserved.