Effects of pregabalin on behavioral alterations induced by ketamine in rats

Objective: The aim of this study is to investigate the effects of pregabalin on the behavior of rats under the influence of ketamine, an NMDA receptor antagonist that mimics the symptoms of schizophrenia. Methods: Rats were injected with saline or 25 mg/kg ketamine intraperitoneally. After that, behavior modifications were investigated by the evaluation of stereotypy and hyperlocomotion, after treating rats with pregabalin (at doses of 30 mg/kg or 100 mg/kg) or placebo (saline solution). Results: The administration of pregabalin reduced ketamine-induced hyperlocomotion. However, neither doses of pregabalin had a significant effect on ketamine-induced stereotypy. Conclusion: This is the first study to investigate the effects of pregabalin using an animal model of psychosis. Furthermore, our results indicate that behavioral changes induced by ketamine in rats can be reversed with the use of pregabalin, suggesting its potential to treat psychotic symptoms.

NLRP3 inflammasome-mediated neutrophil recruitment and hypernociception depend on leukotriene B4 in a murine model of gout

Objective Deposition of monosodium urate monohydrate (MSU) crystals in the joints promotes an intense inflammatory response and joint dysfunction. This study evaluated the role of the NLRP3 inflammasome and 5-lipoxygenase (5-LOX)derived leukotriene B4 (LTB4) in driving tissue inflammation and hypernociception in a murine model of gout. Methods. Gout was induced by injecting MSU crystals into the joints of mice. Wild-type mice and mice deficient in NLRP3, ASC, caspase 1, interleukin-1 beta (IL-1 beta), IL-1 receptor type I (IL-1RI), IL-18R, myeloid differentiation factor 88 (MyD88), or 5-LOX were used. Evaluations were performed to assess neutrophil influx, LTB4 activity, cytokine (IL-1 beta, CXCL1) production (by enzyme-linked immunosorbent assay), synovial microvasculature cell adhesion (by intravital microscopy), and hypernociception. Cleaved caspase 1 and production of reactive oxygen species (ROS) were analyzed in macrophages by Western blotting and fluorometric assay, respectively. Results. Injection of MSU crystals into the knee joints of mice induced neutrophil influx and neutrophildependent hypernociception. MSU crystal-induced neutrophil influx was CXCR2-dependent and relied on the induction of CXCL1 in an NLRP3/ASC/caspase 1/IL-1 beta/MyD88-dependent manner. LTB4 was produced rapidly after injection of MSU crystals, and this was necessary for caspase 1-dependent IL-1 beta production and consequent release of CXCR2-acting chemokines in vivo. In vitro, macrophages produced LTB4 after MSU crystal injection, and LTB4 was relevant in the MSU crystalinduced maturation of IL-1 beta. Mechanistically, LTB4 drove MSU crystal-induced production of ROS and ROS-dependent activation of the NLRP3 inflammasome. Conclusion. These results reveal the role of the NLRP3 inflammasome in mediating MSU crystalinduced inflammation and dysfunction of the joints, and highlight a previously unrecognized role of LTB4 in driving NLRP3 inflammasome activation in response to MSU crystals, both in vitro and in vivo.

Physiological effects of glyphosate over amino acid profile in conventional and transgenic soybean (Glycine max)

This paper compares the responses of conventional and transgenic soybean to glyphosate application in terms of the contents of 17 detectable soluble amino acids in leaves, analyzed by HPLC and fluorescence detection. Glutamate, histidine, asparagine, arginine + alanine, glycine + threonine and isoleucine increased in conventional soybean leaves when compared to transgenic soybean leaves, whereas for other amino acids, no significant differences were recorded. Univariate analysis allowed us to make an approximate differentiation between conventional and transgenic lines, observing the changes of some variables by glyphosate application. In addition, by means of the multivariate analysis, using principal components analysis (PCA), cluster analysis (CA) and linear discriminant analysis (LDA) it was possible to identify and discriminate different groups based on the soybean genetic origin. (C) 2011 Elsevier Inc. All rights reserved.

Chronic Intermittent Hypoxia Depresses Afferent Neurotransmission in NTS Neurons by a Reduction in the Number of Active Synapses

Long-term synaptic plasticity has been recently described in brainstem areas associated to visceral afferent sensory integration. Chronic intermittent hypoxia (CIH), an animal model for studying obstructive sleep apnea in humans, depresses the afferent neurotransmission in nucleus tractus solitarii (NTS) neurons, which affect respiratory and autonomic regulation. Here we identified the synaptic mechanisms of CIH-induced depression of the afferent neurotransmission in NTS neurons in juvenile rats. We verified that CIH reduced the amplitude of both NMDA and non-NMDA glutamatergic excitatory currents (eEPSCs) evoked by tractus solitarii stimulation (TS-eEPSC) of second-order neurons in the NTS. No changes were observed in release probability, evidenced by absence of any CIH-elicited effects on short-term depression and failures in EPSCs evoked in low calcium. CIH also produced no changes in TS-eEPSC quantal size, since the amplitudes of both low calcium-evoked EPSCs and asynchronous TS-eEPSCs (evoked in the presence of Sr2+) were unchanged. Using single TS afferent fiber stimulation in slices from control and CIH rats we clearly show that CIH reduced the quantal content of the TS-eEPSCs without affecting the quantal size or release probability, suggesting a reduction in the number of active synapses as the mechanism of CIH induced TS-eEPSC depression. In accordance with this concept, the input-output relationship of stimulus intensity and TS-eEPSC amplitude shows an early saturation in CIH animals. These findings open new perspectives for a better understanding of the mechanisms underlying the synaptic plasticity in the brainstem sensory neurons under challenges such as those produced by CIH in experimental and pathological conditions.