Navegando por Palavras-chave "NMDA"

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    Amyloid beta-peptide activates nuclear factor-kappa B through an N-methyl-D-aspartate signaling pathway in cultured cerebellar cells
    (Wiley-Blackwell, 2008-03-01) Kawamoto, Elisa Mitiko; Lepsch, Lucilia Brochado; Boaventura, Maria Fernanda Cury; Munhoz, Carolina Demarchi; Lima, Larissa de Sá; Yshii, Lidia Mitiko; Avellar, Maria Christina Werneck [UNIFESP]; Curi, Rui; Mattson, Mark P.; Scavone, Cristoforo; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); NIA
    Amyloid P-peptide (A beta) likely causes functional alterations in neurons well prior to their death. Nuclear factor-kappa B (NF-kappa B), a transcription factor that is known to play important roles in cell survival and apoptosis, has been shown to be modulated by A beta in neurons and glia, but the mechanism is unknown. Because A beta has also been shown to enhance activation of N-methyl-D-aspartate (NMDA) receptors, we investigated the role of NMDA receptor-mediated intracellular signaling pathways in A beta-induced NF-kappa B activation in primary cultured rat cerebellar cells. Cells were treated with different concentrations of A beta 1-40 (1 or 2 mu M) for different periods (6, 12, or 24 hr). MK-801 (NMDA antagonist), manumycin A and FTase inhibitor 1 (farnesyltransferase inhibitors), PP1 (Src-family tyrosine kinase inhibitor), PD98059 [mitogen-activated protein kinase (MAPK) inhibitor], and LY294002 [phosphatidylinositol 3-kinase (PI3-k) inhibitor] were added 20 min before A beta treatment of the cells. A beta induced a time- and concentration-dependent activation of NF-kappa B (1 mu M, 12 hr); both p50/p65 and p50/p50 NF-kappa B dimers were involved. This activation was abolished by MK-801 and attenuated by manumycin A, FTase inhibitor 1, PP1, PD98059, and LY294002. AP at 1 mu M increased the expression of inhibitory protein I kappa B, brain-derived neurotrophic factor, inducible nitric oxide synthase, tumor necrosis factor-alpha, and interleukin-1 beta as shown by RTPCR assays. Collectively, these findings suggest that AP activates NF-kappa B by an NMDA-Src-Ras-like protein through MAPK and PI3-k pathways in cultured cerebellar cells. This pathway may mediate an adaptive, neuroprotective response to A beta. (c) 2007 Wiley-Liss, Inc.
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    Atypical antipsychotic olanzapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection of dizocilpine (MK-801) into the inferior colliculus in rats
    (Elsevier B.V., 2013-11-15) Zangrando, Julia [UNIFESP]; Carvalheira, Renata [UNIFESP]; Labbate, Giovanna Puosso [UNIFESP]; Medeiros, Priscila [UNIFESP]; Longo, Beatriz Monteiro [UNIFESP]; Melo-Thomas, Liana [UNIFESP]; Silva, Regina Cláudia Barbosa da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). MK-801 is an NMDA receptor-antagonist known to produce hyperactivity, deficits in prepulse inhibition and social withdrawal, behaviors which correlate well with some of the positive, cognitive and negative symptoms of schizophrenia. the inferior colliculus (IC) is a critical part of the auditory pathway mediating acoustic PPI. the activation of the IC by the acoustic prepulse reduces startle magnitude. Thus, the purpose of the present study was to elucidate the role of glutamatergic transmission in the IC on the expression of acoustic PPI. for that we investigated whether NMDA receptor stimulation or blockade would affect this response. Unilateral microinjections of NMDA (30 nmol/0.5 mu L) into the IC did not alter PPI while microinjections of MK-801 (30 nmol/0.5 mu L) into this structure disrupted PPI. We also examined the ability of the atypical antipsychotic olanzapine (5.0 mg/kg; i.p.) to reverse the disruption of pre-pulse inhibition produced by unilateral microinjections of MK-801 into the IC of rats. Pretreatment with olanzapine blocked MK-801-induced disruption of PPI. Altogether, these results suggest that glutamate-mediated mechanisms of the IC are involved in the expression of PPI in rodents and that this response is sensitive to atypical antipsychotic olanzapine. (C) 2013 Elsevier B.V. All rights reserved.
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    Avaliação da eficácia do nitroprussiato de sódio no tratamento de déficits cognitivos de indivíduos com esquizofrenia resistente ao tratamento: um estudo duplo-cego, randomizado, controlado por placebo
    (Universidade Federal de São Paulo (UNIFESP), 2021) Costa Junior, Edivarley Rodrigues da [UNIFESP]; Lacerda, Acioly Luiz Tavares De [UNIFESP]; Universidade Federal de São Paulo
    Schizophrenia is a severe neuropsychiatric disease, with great impact on the patient, family and society and, despite important advances, its etiology and pathophysiology are still unknown. In the first descriptions of schizophrenia, cognitive symptoms have been considered core symptoms of the disease and have been associated with greater impairment in functioning. About one third of patients do not respond to conventional treatments with antipsychotics (dopaminergic antagonists), being considered resistant to treatment (TRS). Glutamate is the main excitatory neurotransmitter in the central nervous system and is involved in major cognitive functions such as memory and learning. One of the main evidences for the glutamatergic hypothesis comes from the psychotic syndrome induced by drugs blocking NMDA receptors, such as phencyclidine and ketamine. A proposed treatment for schizophrenia involves drugs that modulate nitric oxide, since it is a major modulator of the glutamatergic neurotransmission. Recent studies have suggested that sodium nitroprusside (SNP), a nitric oxide donor, is effective for the treatment of different symptomatic domains of schizophrenia, including positive, negative, depressive, cognitive and anxiety symptoms. Considering that, by definition, treatment-resistant schizophrenia does not respond satisfactorily to treatment with dopaminergic antagonists, in the present study we hypothesized that this subgroup would respond to an alternative mechanism of action such as modulation of the glutamatergic system through the administration of sodium nitroprusside This double-blind, randomized, placebo-controlled clinical trial aimed to examine the efficacy of repeated doses of SNP for the treatment of cognitive symptoms in schizophrenia. Twenty patients (18 to 60 years of age) with a history of non-response to ≥ 2 antipsychotics were enrolled. Patients received SNP or placebo in 4 infusions of 0.5 µg / kg / min over 4 hours. Cognitive symptoms were assessed with the Stroop Test, N-Back and verbal fluency test. SNP and placebo groups did not differ at baseline or in change from baseline over the 8 assessments. Although there were increases in blood pressure in the SNP group, it showed good tolerability and safety. Although preliminary, the present findings suggest that SNP is not effective for the treatment of cognitive symptoms in TRS, reinforcing the results of previous studies that have not shown efficacy in the treatment of chronic patients. At this point, it is conceivable to speculate that the effectiveness of the SNP may be restricted to early stages of the disease.
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    Behavioral sensitization to ethanol results in cross-sensitization to MK-801 but not to NMDA administered intra-accumbens
    (Elsevier B.V., 2012-12-01) Abrahao, Karina Possa [UNIFESP]; Oliveira Souza-Formigoni, Maria Lucia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    In mice, repeated ethanol administration may induce behavioral sensitization - a process of progressive potentiation of its stimulant effects, associated with neuroadaptations in the brain reward system. Few studies have directly investigated the subsequent neuroadaptations in the nucleus accumbens (NAc), the central area of the brain reward system, after chronic ethanol administration. the goal of the present study was to analyze the involvement of accumbal glutamate NMDA receptors in the locomotion behavioral response to an NMDA agonist or to an NMDA antagonist in mice previously treated with ethanol. Swiss Albino mice received repeated daily administrations of 2.2 g/kg ethanol or saline for 21 days. According to their locomotor response on the last day of treatment, ethanol-treated mice were classified into sensitized or non-sensitized groups. They were then submitted to a surgical procedure to implement intra-NAc cannulae. After recovery, mice were challenged with intra-NAc administration of saline and, two days later, with NMDA (NMDA agonist) or MK-801 (NMDA antagonist), having their locomotor activity recorded for 1 h. the administration of NMDA induced similar locomotor behavior in all groups. On the other hand, the administration of 3 mu g/side MK-801 induced a significant stimulant effect which was more prominent during the first 15 min in the sensitized group than in the non-sensitized or saline groups. Despite no effect of the agonist administration, only in sensitized mice did we observe cross-sensitization between repeated ethanol treatment and the intra-NAc administration of MK-801. (C) 2012 Elsevier B.V. All rights reserved.
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    Chronic unpredictable stress exacerbates lipopolysaccharide-induced activation of nuclear factor-kappa B in the frontal cortex and hippocampus via glucocorticoid secretion
    (Soc Neuroscience, 2006-04-05) Munhoz, Carolina Demarchi; Lepsch, Lucilia Brochado; Kawamoto, Elisa Mitiko; Malta, Marília Brinati; Lima, Larissa de Sá; Avellar, Maria Christina Werneck [UNIFESP]; Sapolsky, Robert M.; Scavone, Cristoforo; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Stanford Univ
    Although the anti-inflammatory actions of glucocorticoids (GCs) are well established in the periphery, these stress hormones can increase inflammation under some circumstances in the brain. the transcription factor nuclear factor-kappa B (NF-kappa B), which is inhibited by GCs, regulates numerous genes central to inflammation. in this study, the effects of stress, GCs, and NMDA receptors on lipopolysaccharide (LPS)-induced activation of NF-kappa B in the brain were investigated. One day after chronic unpredictable stress (CUS), nonstressed and CUS rats were treated with saline or LPS and killed 2 h later. CUS potentiated the increase in LPS-induced activation of NF-kappa B in frontal cortex and hippocampus but not in the hypothalamus. This stress effect was blocked by pretreatment of rats with RU-486, an antagonist of the GC receptor. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate], an NMDA receptor antagonist, also reduced the effect of LPS in all three brain regions. However, the combined antagonism of both GC and NMDA receptors produced no further reduction in NF-kappa B activation when compared with the effect of each treatment alone. Our results indicate that stress, via GC secretion, can increase LPS-induced NF-kappa B activation in the frontal cortex and hippocampus, agreeing with a growing literature demonstrating proinflammatory effects of GCs.
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    Efeitos das infusões de muscimol e AP5 no subículo dorsal sobre a aquisição e a consolidação do condicionamento de medo ao contexto em ratos
    (Universidade Federal de São Paulo (UNIFESP), 2019-11-28) Braga de Melo, Márcio [UNIFESP]; Oliveira, Maria Gabriela Menezes de [UNIFESP]; http://lattes.cnpq.br/4960400313077156; http://lattes.cnpq.br/8003168917392878; Universidade Federal de São Paulo (UNIFESP)
    The dorsal hippocampus (DH) has a well-known role in the contextual fear conditioning (CFC) and spatial information. Involvement of the DH in CFC has been established by showing that its muscimol-induced temporary inactivation impairs CFC consolidation while acquisition is hindered by blocking DH glutamatergic NMDA receptors with AP5. The dorsal subiculum (DSub) is also involved in spatial information and it is necessary for retrieval of the CFC. Moreover, the DSub is a major output from the hippocampus through pathways that seemingly relies on NMDA-dependent synaptic plasticity. However, the implication of the DSub in the CFC consolidation is still unclear. Our aim was to assess the effects of intra-DSub muscimol or AP5 infusion on CFC acquisition and consolidation. The DSub of 3-to-4-month-old male Wistar rats were bilaterally cannulated (AP=-6.4 mm, ML=±3.8 mm, DV=- 3.4 mm). CFC training consisted of applying a footshock (1s/0.8mA – after a 120s delay) as the unconditioned stimulus. A 5-min test was done 48h later, and freezing was assessed as the behavioral conditioned response. All groups received 0.2ul/hemisphere infusions 5min before or immediately after the training. Data from animals with incorrect cannula implantation were excluded. To control for bias such as shock sensitivity and emotional reaction, we employed a hippocampal-independent procedure: step-through inhibitory avoidance (ST IA). Freezing was analyzed by the generalized estimating equations (GEE) method, with group and time-bin (minute-by-minute) as independent factors. IAST latency was analyzed by generalized linear model (GzLM), with group as the only independent factor. LSD posthoc test was applied when appropriate. The pre or posttraining intra-DSub muscimol infusion impairs the CFC. The pre-training intra-DSub AP5 infusion did not impair CFC, but the post-training manipulation did. Our data, together with the literature, suggest that the integrity of the DSub, as structure, is necessary only for the CFC consolidation. Furthermore, the NMDA receptors in this region are also necessary for the consolidation, but not for the CFC acquisition, a different pattern from the observed in the DH. The lack of drug effect on ST IA latency indicates that controlled factors did not account for the observed differences.
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    Effects of pre- or post-training entorhinal cortex AP5 injection on fear conditioning
    (Elsevier B.V., 2005-11-15) Schenberg, E. E.; Soares, JCK; Oliveira, MGM; Universidade Federal de São Paulo (UNIFESP)
    Fear conditioning is one of the most studied paradigms to assess the neural basis of emotional memory. the circuitry involves NNMA receptor activation in the amygdala and, in the case of contextual conditioning, in the hippocampus. Entorhinal cortex is one of the major input/output structures to the hippocampus and also projects to the amygdala, both through glutamatergic transmission. Other learning tasks involving hippocampus and amygdala, such as inhibitory avoidance, require entorhinal cortex during acquisition and consolidation. However, the involvement of NMDA receptors mediated transmission in entorhinal cortex in fear conditioning acquisition and consolidation is not clear. To investigate that issue, rats were trained in fear conditioning to both contextual and tone conditioned stimulus. Immediately before, immediately, 30 or 90 min after training they received NMDA antagonist AP5 or saline injections bilaterally in the entorhinal cortex (AP-6.8 mm, L +/- 5.0 mm DV-6.8 mm). Contextual fear conditioning was measured 24 h after training, and tone fear conditioning 48 h after training. AP5 injections selectively impaired contextual fear conditioning only when injected pre-training. Post-training injections had no effect. These findings suggest that entorhinal cortex NMDA receptors are necessary for acquisition, but not for consolidation, of contextual fear conditioning. On the other hand, both acquisition and consolidation of tone fear conditioning seem to be independent of NMDA receptors in the entorhinal cortex. (c) 2005 Elsevier Inc. All fights reserved.
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    Fear conditioning performance and NMDA receptor subtypes: NR2A differential expression in the striatum
    (Elsevier B.V., 2006-04-28) Schenberg, E. E.; Ferreira, T. L.; Figueredo, L. Z.; Hipolide, D. C.; Nobrega, J. N.; Oliveira, MGM; Universidade Federal de São Paulo (UNIFESP); Ctr Addict & Mental Hlth
    While considerable evidence implicates NMDA receptors in the hippocampus in contextual fear conditioning, the role of other brain regions is less well understood. To further investigate this issue, rats were subjected to a contextual fear conditioning task and then classified as high or low responders according to performance. Density of NMDA receptors was evaluated using [H-3]MK-801 autoradiography in 52 brain areas and expression of NR2A and NR2B subunits was studied with in situ hybridization in the same brains. Results revealed no differences between high- and low-performance rats in NMDA receptor binding in any of the brain areas studied. Similarly, NR2B subunit expression was also not different between groups. However, NR2A expression was significantly higher in the caudate-putamen of low-performance rats. These results suggest that NMDA receptors in the caudate-putamen may also be involved in contextual fear conditioning performance. (c) 2006 Elsevier Inc. All rights reserved.
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    Functional specializations within the tectum defense systems of the rat
    (Elsevier B.V., 2005-01-01) Schenberg, L. C.; Povoa, RMF; Costa, ALP; Caldellas, A. V.; Tufik, S.; Bittencourt, A. S.; Univ Fed Espirito Santo; Universidade Federal de São Paulo (UNIFESP)
    Here we review the differential contribution of the periaqueductal gray matter (PAG) and superior colliculus (SC) to the generation of rat defensive behaviors. the results of studies involving sine-wave and rectangular pulse electrical stimulation and chemical (NMDA) stimulation are summarized. Stimulation of SC and PAG produced freezing and flight behaviors along with exophthalmus (fully opened bulged eyes), micturition and defecation. the columnar organization of the PAG was evident in the results obtained. Defecation was elicited primarily by lateral PAG stimulation, while the remaining defensive behaviors were similarly elicited by lateral and dorsolateral PAG stimulation, although with the lowest thresholds in the dorsolateral column. Conversely, the ventrolateral PAG did not appear to participate in unconditioned defensive behaviors, which were only elicited by high intensity stimulation likely to encroach on adjacent regions. in the SC, the most important differences relative to the PAG were the lack of stimulation -evoked jumping in both intermediate and deep layers, and of NMDA-evoked galloping in intermediate layers. Therefore, we conclude that the SC may be only involved in the increased attentiveness (exophthalmus, immobility) and restlessness (trotting) of prey species exposed to the cues of a nearby predator. These responses may be distinct from the full-blown flight reaction that is mediated by the dorsolateral and lateral PAG. However, other evidences suggest the possible influences of stimulation schedule, environment dimensions and rat strain in determining outcomes. Overall our results suggest a dynamically organized representation of defensive behaviors in the midbrain tectum. (c) 2005 Elsevier B.V. All rights reserved.
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    Glutamatergic neurotransmission in the inferior colliculus influences intrastriatal haloperidol-induced catalepsy
    (Elsevier B.V., 2014-07-15) Medeiros, Priscila [UNIFESP]; Viana, Milena de Barros [UNIFESP]; Silva, Regina Cláudia Barbosa da [UNIFESP]; Tonelli, Luan Castro [UNIFESP]; Melo-Thomas, Liana [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Inst Neurociencias & Comportamento INEC
    The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. in addition, it has also been implicated in the processing of acoustic information of aversive nature, as well as in sensory-motor gating. There is evidence that glutamate-mediated mechanisms at the IC level influence haloperidol-induced catalepsy. the present study investigated the influence of glutamate-mediated mechanisms in the IC on catalepsy induced by intrastriatal microinjection of haloperidol (10 mu g/0.5 mu l). Male Wistar rats received bilateral intracollicular microinjections of the glutamate receptor agonist NMDA (10 or 20 nmol/0.5 mu l), the NMDA receptor antagonists MK-801 (15 or 30 nmol/0.5 mu l) or physiological saline (0.5 mu l), followed by bilateral microinjections of haloperidol (10 mu g/0.5 mu l) or vehicle (0.5 mu l) into the dorso-rostral or ventro-rostral striatum. the catalepsy test was performed positioning both forepaws of the rats on an elevated horizontal wooden bar and recording the time during which the animal remained in this position. the results showed that the administration of physiological saline in the IC followed by the microinjection of haloperidol in the dorso-rostral region of the striatum was not able to induce catalepsy. However, when the bilateral administration of NMDA into the IC was followed by microinjection of haloperidol into the dorso-rostral striatum, catalepsy was observed. the microinjection of haloperidol into the ventro-rostral striatum induced catalepsy, counteracted by previous administration of MK-801 into the IC. These findings suggest that glutamate-mediated mechanisms in the IC can influence the intrastriatal haloperidol-induced catalepsy and that the IC plays an important role as a sensorimotor interface. (C) 2014 Elsevier B.V. All rights reserved.
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    Modulação do extrato padronizado de Ginkgo biloba na expressao dos receptores NMDA-NR2B e 5HT1A e de astrócitos em diferentes regiões da formação hipocampal doral de ratos submetidos à aquisição da supressão condicionada da resposta lamber
    (Universidade Federal de São Paulo, 2014-09-25) Tilger, Myrcea Andressa de Souza [UNIFESP]; Cerutti, Suzete Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The brain’s ability to adapt and change its structure, connectivity and functional properties over time characterizes neural plasticity, which can be investigated using different approaches. Memory formation has been recognized as a stimulant of brain plasticity, which is often characterized by neuronal and glial adaptations. Our group has been evaluated neural plasticity by means of the analysis of behavioural and morphological correlates. The present study investigated the astroglial reaction employing glial fibrillary acidic protein immunohistochemistry (GFAP-IR) in the hippocampal formation. (CA1, CA3 and GD) with one dose before fear conditioning of EGb (250 mg.Kg-1, 500 mg.Kg-1 and 1000 mg.Kg-1),vehicle (Tween® and Saline), agonists (10.0mg.Kg-1 Buspirone or 10mg.Kg-1N-methyl D-aspartate), antagonists (0.3 mg.Kg-1 (S)-WAY 100135 or 3.0 mg.Kg-1Ro25-6981) of the 5-HT1ARs or NMDARs/GluN2B and antagonists+EGb ((S)-WAY+EGb or Ro+EGb) (n=3/group). Further, negative control groups (saline 0.9% i.p. and Tween 80 12% v.o.), no-footshock group (CS) and conditioned group (CS-US association) were used. Twenty-four hours after the behavioral experiments were performed, the rats (n=3/group) were deeply anesthetized and perfused with 4% paraformaldehyde. After decapitation, the brains were removed, post fixed, cryoprotected in 10% sucrose, frozen and stored at -80ºC until use. Adjacent serial 20-µm-thick coronal brain sections were obtained with a cryostat and mounted on gelatin-coated slices. These sections integrated two levels including formation hippocampal rostral and caudal (coordinates -2.04 to-4.20 mm from bregma). At each region, 4 fields were analyzed bilaterally. Images were acquired using AxioVision software (Carl Zeiss, Axion imager A2). ImageJ software was employed for quantification of the immunoreactive labeling in CA1, CA3 and GD. An increased number of GFAP-IR astrocytes were found in the CA1, CA3 and GD (P<0.05) of the EGb groups. GFAP-IR was increased in the CA3 and GD in Buspirone group (P<0.05). However, no significant changes were observed to NMDA groups (P>0.05). Additionally, the overexpression of GFAP was reversed by treatment with (S)-WAY 100135 or Ro25-6981 prior EGb. Our results provide further evidence that astroglial reaction in the hippocampal formation may be involved in neuroplastic response in those regions. The fear memory/treatment-dependent changes suggest that EGb might be effective for memory enhancement through its effect on the astrocytes cells which seems to be modulate by NMDA-type of glutamate as well as by serotoninergic-type5HT1A receptors.
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    Neuromodulatory effect of creatine on extracellular action potentials in rat hippocampus: Role of NMDA receptors
    (Elsevier B.V., 2008-07-01) Freire Royes, Luiz Fernando; Fighera, Michele Rechia; Furian, Ana Flavia; Oliveira, Mauro Schneider; Fiorenza, Natalia Gindri; Ferreira, Juliano; Silva, Andre Cesar da [UNIFESP]; Priel, Margareth Rose [UNIFESP]; Ueda, Erika Sayuri [UNIFESP]; Calixto, Joao Batista; Cavalheiro, Esper Abrao [UNIFESP]; Mello, Carlos Fernando; Universidade Federal de Sergipe (UFS); Univ Fed Rio Grande do Sul; Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Santa Catarina (UFSC)
    The creatine (Cr) and phosphocreatine (PCr) system is essential for the buffering and transport of high-energy phosphates. Although achievements made over the last years have highlighted the important role of creatine in several neurological diseases, the adaptive processes elicited by this guanidino compound in hippocampus are poorly understood. in the present study, we showed that creatine (0.5-25 mM) gradually increases the amplitude of first population spike (PS) and elicits secondary PS in stratum radiatum of the CA1 region, in hippocampal slices. Creatine also decreased the intensity of the stimulus to induce PS, when compared with hippocampal slices perfused with artificial cerebrospinal fluid (ACSF). the competitive NMDA receptor antagonist, 2-amino-5-phosphonopentanoic acid (AP5; 100 mu M) attenuated creatine-induced increase of amplitude of PS and appearance of secondary PS, providing pharmacological evidence of the involvement of NMDA receptors in the electrophysiological effects of creatine. Accordingly, creatine (0.01-1 mM) increased [H-3]MK-801 binding to hippocampal membranes by 55%, further indicating that this compound modulates NMDA receptor function. These results implicate the NMDA receptor in amplitude and population spike increase elicited by creatine in hippocampus. Furthermore, these data suggest that this guanidino compound may also play a putative role as a neuromodulator in the brain, and that at least some of its effects may be mediated by an increase in glutamatergic function. (c) 2008 Elsevier B.V. All rights reserved.
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    Organization of single components of defensive behaviors within distinct columns of periaqueductal gray matter of the rat: Role of N-methyl-D-aspartic acid glutamate receptors
    (Elsevier B.V., 2004-01-01) Bittencourt, A. S.; Carobrez, A. P.; Zamprogno, L. P.; Tufik, S.; Schenberg, L. C.; Univ Fed Espirito Santo; Universidade Federal de Santa Catarina (UFSC); Universidade Federal de São Paulo (UNIFESP)
    The periaqueductal gray matter (PAG) is functionally organized in longitudinal columns arranged along the aqueduct. Stimulation of lateral and dorsal columns produces a complex set of unconditioned behaviors named the 'defense reaction.' Overt responses in rats comprise a tense immobile display, fully opened eyes (herein named exophthalmus), trotting, galloping, jumping, micturition and defecation. Besides, the PAG is rich in glutamate and respective receptors, including the N-methyl-D-aspartic acid (NMDA) type. Therefore, the present study employed regression analysis to map out electrically and NMDA-induced single components of defensive behaviors produced by stepwise increasing stimulation of PAG. Data confirmed the defensive nature of PAG-evoked responses. Neither the appetitive, nor offensive, mouse-killing or male reproductive behaviors were produced by stimulation of PAG in presence of appropriate targets. Threshold and dose-response logistic analyses largely corroborated the columnar organization of PAG-evoked responses. Thus, whereas the defecation was restricted to PAG lateral column, exophthalmus, micturition and somatic defensive responses were similarly organized in dorsolateral and lateral, but not in the ventrolateral column. Moreover, thresholds of dorsolateral and lateral repertoires were strictly hierarchical, with exophthalmus, immobility, trotting, galloping and jumping appearing in this very order. However, the defensive responses of PAG dorsolateral column required NMDA doses significantly lower than those of lateral PAG. Accordingly, NMDA receptors within the dorsolateral PAG are likely to play a major role in the initiation of PAG-evoked defensive responses. in contrast, the present data do not support the organization of unconditioned defensive behaviors in ventrolateral PAG. the neuroanatomical substrate of each response and the role of PAG and NMDA receptors are discussed in relation to the present data. Further, this is the first report on PAG columnar organization of single components of defensive behaviors. (C) 2004 IBRO. Published by Elsevier B.V. All rights reserved.
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    Ouabain activates NF kappa B through an NMDA signaling pathway in cultured cerebellar cells
    (Elsevier B.V., 2013-10-01) Lima, Larissa de Sá; Kawamoto, Elisa Mitiko; Munhoz, Carolina Demarchi; Kinoshita, Paula Fernanda; Orellana, Ana Maria Marques; Curi, Rui; Rossoni, Luciana Venturini; Avellar, Maria Christina Werneck [UNIFESP]; Scavone, Cristoforo; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Na,K-ATPase, an ion pump, has been shown to interact with other proteins in signaling complexes in cardiac myocytes, renal and glial cells, and several other cell types. Our previous in vivo studies indicated that intrahippocampal administration of ouabain (QUA), an inhibitor of Na,K-ATPase, induces NF kappa B activation, leading to an increase in mRNA levels of target genes of this transcription factor in the rat hippocampus. the present work investigated whether QUA can regulate NF-kappa B in primary cultured rat cerebellar cells. Cells were treated with different concentrations of QUA (1, 10 or 100 mu M) for different periods of time (1, 2 and 4 h). QUA induced a time- and concentration-dependent activation of NF kappa B (peak of activation: 10 mu M, 2 h), involving both p50/p65 and p50/p50 NF kappa B dimers. QUA (10 mu M, 2 h) induced upregulation of tumor necrosis factor alpha (Tnf-alpha), interleukin-1 beta(Il-1 beta), and brain derived neurotrophic factor (Bdnf) mRNA levels. Both NF kappa B activation and gene expression activation induced by QUA (10 mu M) were abolished when cells were pre-treated for 20 min with MK-801 (N-Methyl-D-Aspartate (NMDA) receptor antagonist), manumycin A (farnesyltransferase inhibitor), PP-1(Src-family tyrosine kinase inhibitor) and PD98059 (mitogen-activated protein kinase (MAPK) inhibitor). QUA (10 mu M) alone or in the presence of MK-801, PP-1, PD98059 did not cause cell death or DNA fragmentation. These findings suggest that QUA activates NF kappa B by NMDA-Src-Ras-like protein through MAPK pathways in cultured cerebellar cells. This pathway may mediate an adaptive response in the central nervous system. Published by Elsevier B.V.