Neuromodulation and neuroprotective effects of chlorogenic acids in excitatory synapses of mouse hippocampal slices

The increased healthspan afforded by coffee intake provides novel opportunities to identify new therapeutic strategies. Caffeine has been proposed to afford benefits through adenosine A2A receptors, which can control synaptic dysfunction underlying some brain disease. However, decaffeinated coffee and other main components of coffee such as chlorogenic acids, also attenuate brain dysfunction, although it is unknown if they control synaptic function. We now used electrophysiological recordings in mouse hippocampal slices to test if realistic concentrations of chlorogenic acids directly affect synaptic transmission and plasticity. 3-(3,4-dihydroxycinnamoyl)quinic acid (CA, 1–10 μM) and 5-O-(trans-3,4-dihydroxycinnamoyl)-D-quinic acid (NCA, 1–10 μM) were devoid of effect on synaptic transmission, paired-pulse facilitation or long-term potentiation (LTP) and long-term depression (LTD) in Schaffer collaterals-CA1 pyramidal synapses. However, CA and NCA increased the recovery of synaptic transmission upon re-oxygenation following 7 min of oxygen/glucose deprivation, an in vitro ischemia model. Also, CA and NCA attenuated the shift of LTD into LTP observed in hippocampal slices from animals with hippocampal-dependent memory deterioration after exposure to β-amyloid 1–42 (2 nmol, icv), in the context of Alzheimer’s disease. These findings show that chlorogenic acids do not directly affect synaptic transmission and plasticity but can indirectly affect other cellular targets to correct synaptic dysfunction. Unraveling the molecular mechanisms of action of chlorogenic acids will allow the design of hitherto unrecognized novel neuroprotective strategies

Piperine decreases pilocarpine-induced convulsions by GABAergic mechanisms

Piperine, an alkaloid present in the Piper genus, was shown to have an anticonvulsant activity, evaluated by the pilocarpine-induced model, in mice. Pilocarpine (350 mg/kg, i.p.) was administered 30 min after piperine (2.5, 5, 10 and 20 mg/kg, i.p.) which significantly increased latencies to 1st convulsion and to death, and percentage of survivals. These parameters were also increased in the pilocarpine groups pretreated with atropine plus piperine (10 and 2.5 mg/kg, respectively), as related to the pilocarpine group. However, they were not altered in the pilocarpine groups pretreated with memantine (a NMDA-type glutamate receptors blocker, 2 mg/kg, p.o.) or nimodipine (a calcium channel blocker, 10 mg/kg, p.o.), both associated with piperine (1 or 2.5 mg/kg), as compared to the piperine plus pilocarpine group. Moreover, the pilocarpine group pretreated with diazepam (which binds to the GABA(A) receptor, 0.2 and 0.5 mg/kg, i.p.) plus piperine (1 and 2.5 mg/kg) significantly increased latency to the 1st convulsion, as related to the pilocarpine group, suggesting that the GABAergic system is involved with the piperine action. Furthermore, the piperine effect was blocked by flumazenil (2 mg/kg, i.p.), a benzodiazepine antagonist. Untreated P350 animals showed decreased striatal DA and increased DOPAC and HVA levels that were not affected in the piperine plus pilocarpine groups. Piperine increased striatal levels of GABA, glycine and taurine, and reversed pilocarpine-induced increases in nitrite contents in sera and brain. Hippocampi from the untreated pilocarpine group showed an increased number of TNF-alpha immunostained cells in all areas, as opposed to the pilocarpine group pretreated with piperine. Taken together, piperine anticonvulsant effects are the result of its anti-inflammatory and antioxidant actions, as well as TNF-alpha reduction. in addition, piperine effects on inhibitory amino acids and on the GABAergic system may certainly contribute to the drug anticonvulsant activity. (C) 2013 Elsevier Inc. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FMJ, Fac Med Estacio Juazeiro Norte, Fortaleza, Ceara, BrazilUniversidade Federal de São Paulo, UNIFESP, São Paulo, BrazilUniv Fed Ceara, Fac Med, UFC, Fortaleza, Ceara, BrazilUniversidade Federal de São Paulo, UNIFESP, São Paulo, BrazilWeb of Scienc

Minocycline exerts a neuroprotective action against 6-OHDA-induced neurotoxicity: in vivo and in vitro studies

Background: Parkinson’s disease (PD) is a chronic neurological disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The oxidative stress and inflammation, among other factors, are involved in the mechanisms of cell death in PD. We studied the neuroprotective properties of minocycline (Mino), focusing on its behavioral, neurochemical and immunohistochemical effects. Besides, Mino effects were also studied on an in vitro model of PD, as well as on the release of MPO in human neutrophils, and also its antioxidant activity. Methods: We used in vivo (unilateral injection of 6-OHDA into the right striatum) and in vitro (SH-SY5Y cells) models of PD. For the in vivo model, male Wistar rats were divided into the following groups: sham-operated (SO), 6-OHDA-lesioned and untreated and 6-OHDA-lesioned and treated with Mino (10 and 25 mg/kg, p.o., 7days). The animals were evaluated for behavioral, neurochemical and immunohistochemistry alterations. We also focused on Mino cytoprotective effects, as evaluated by its antioxidant and anti-inflammatory effects (nitrite determination and MPO release). Results: Mino (10 and 25 mg/kg, p.o.) significantly reversed the decrease in striatal DA and DOPAC contents, the alteration in apomorphine-induced rotational behavior and the locomotor activity observed in 6-OHDA-lesioned rats, indicative of neuroprotection. Besides, it decreased the immunoreactivity for TNF-alpha in the hippocampus. In SH-SY5Y cells, Mino increased cells viability, as evaluated by the MTT assay, and significantly decreased the high nitrite levels observed in the cells after 6-OHDA-induced cytotoxicity. Mino presented anti-inflammatory and antioxidant effects as evaluated by inhibition of MPO release (an inflammatory marker) on human neutrophils and DPPH assay. Conclusion: Minocycline exerts neuroprotective effects in vivo and in vitro, decreasing dopaminergic cell loss, through mechanisms that are a consequence of Mino anti-inflammatory and antioxidant properties, pointing out to its potential application for the treatment of neurodegenerative diseases as PD. Â

MICROBIOLOGICAL ASPECTS OF RENNET CHEESE COMMERCIALIZED IN FORTALEZA –CEARA (BRAZIL)

Avaliou-se a qualidade microbiológica de cinqüenta e seis amostras de queijo tipo "coalho" provenientes de diferentes pontos comerciais de Fortaleza Ceará. Foram quantificadas as bactérias mesófilas, Staphylococcus aureus, coliformes totais e fecais, bolores e leveduras. Verificou-se que em relação às contagens de coliformes fecais e Staphylococcus aureus, 67,9% e 62,5% das amostras respectivamente, não atenderam aos padrões estabelecidos pela legislação brasileira em vigor.The microbiological content of 56 samples of "coalho" type cheese sold in Fortaleza-Ceará-Brazil, were evaluated to detect the mesophilic bacterias, Staphylococcus aureus, total and faecal coliforms, molds and yeasts. As the presented results, 67,9% and 62,5% the samples were not according to the defined standards for Faecal Coliforms and Staphylococcus aureusrespectively by the Brazilian government specifications

Pentoxifylline Neuroprotective Effects Are Possibly Related to Its Anti-Inflammatory and TNF-Alpha Inhibitory Properties, in the 6-OHDA Model of Parkinson’s Disease

Pentoxifylline (PTX) is a phosphodiesterase inhibitor with anti-TNF-alpha activity, associated with its anti-inflammatory action. Considering Parkinson’s disease (PD) as a neuroinflammatory disorder, the objectives were to evaluate PTX neuroprotective properties, in a model of PD. Male Wistar rats, divided into sham-operated (SO), untreated 6-OHDA, and 6-OHDA treated with PTX (10, 25, and 50 mg/kg) groups, received a unilateral 6-OHDA injection, except the SO group administered with saline. Treatments started 24 h after surgery and continued for 15 days when the animals were submitted to apomorphine-induced rotations, open field, and forced swimming tests. At the next day, they were euthanized and their striata processed for neurochemical (DA and DOPAC determinations), histological, and immunohistochemical (Fluoro-Jade, TH, DAT, OX-42, TNF-alpha, COX-2, and iNOS) studies. PTX reversed the behavioral changes observed in the untreated 6-OHDA animals. Furthermore, PTX partially reversed the decrease in DA contents and improved neuronal viability. In addition, decreases in immunostaining for TH and dopamine transporter (DAT) were reversed. The untreated 6-OHDA group showed intense OX-42, TNF-alpha, COX-2, and iNOS immunoreactivities, which were attenuated by PTX. In conclusion, we demonstrated a neuroprotective effect of PTX, possibly related to its anti-inflammatory and antioxidant actions, indicating its potential as an adjunct treatment for PD

Behavioral, affective, and cognitive alterations induced by individual and combined environmental stressors in rats

Objective: To evaluate whether exposing rats to individual or combined environmental stressors triggers endophenotypes related to mood and anxiety disorders, and whether this effect depends on the nature of the behavior (i.e., innate or learned). Methods: We conducted a three-phase experimental protocol. In phase I (baseline), animals subjected to mixed schedule of reinforcement were trained to press a lever with a fixed interval of 1 minute and a limited hold of 3 seconds. On the last day of phase I, an open-field test was performed and the animals were divided into four experimental groups (n=8/group). In phase II (repeated stress), each group was exposed to either hot air blast (HAB), paradoxical sleep deprivation (PSD) or both (HAB+PSD group) on alternate days over a 10-day period. Control group animals were not exposed to stressors. In phase III (post-stress evaluation), behavior was analyzed on the first (short-term effects), third (mid-term effects), and fifth (long-term effects) days after repeated stress. Results: The PSD group presented operant hyperactivity, the HAB group presented spontaneous hypoactivity and anxiety, and the HAB+PSD group presented spontaneous hyperactivity, operant hypoactivity, impulsivity, loss of interest, and cognitive impairment. Conclusion: A combination of environmental stressors (HAB and PSD) may induce endophenotypes related to bipolar disorder

Vitamin E does not prevent bone loss and induced anxiety in rats with ligature-induced periodontitis

AbstractObjectiveThe purpose of this study was to investigate the effect of vitamin E on alveolar bone loss (ABL) and anxiety in rats with ligature-induced experimental periodontitis (EP).Material and methodsWistar rats were subjected to ligature-induced EP and treated with vitamin E (500mg/kg, orally) for 9 days. Then anxiety was tested using the elevated plus-maze (EPM) test. All of the animals were euthanised by cervical dislocation on day 11. ABL was analysed morphometrically and histopathologically. Lipid peroxidation quantification, activity of the enzyme superoxide dismutase and immunohistochemistry to tumour necrosis factor-alpha (TNF-α) and inducible isoform of nitric oxide synthases (iNOS) were also tested.ResultsEP induced a marked inflammatory process and intense ABL. Treatment with vitamin E decreased inflammatory reaction, prevented malondialdehyde formation and reduced the immunoreactivity to iNOS, but did not decrease ABL. Vitamin E had an anxiogenic effect on rats with or without EP.ConclusionsVitamin E may have potential to reduce oxidative damage and inflammatory response in EP but does not prevent ABL. Attention should be given to indiscriminate use of vitamin E due to the risk of causing anxiety in patients

Curcumin reverses neurochemical, histological and immuno-histochemical alterations in the model of global brain ischemia

Curcumin, a curcuminoid from Curcuma longa, presents antioxidant and anti-inflammatory actions and, among pathological changes of cerebral ischemic injury, inflammation is an important one. The objectives were to study the neuroprotective action of curcumin, in a model of global ischemia. Male Wistar rats (sham-operated, ischemic untreated and ischemic treated with curcumin, 25 or 50 mg/kg, p.o.) were anesthesized and their carotid arteries occluded, for 30 min. The SO group had the same procedure, except for carotid occlusion. In the 1st protocol, animals were treated 1 h before ischemia and 24 h later; and in the 2nd protocol, treatments began 1 h before ischemia, continuing for 7 days. Twenty four hours after the last administration, animals were euthanized and measurements for striatal monoamines were performed, at the 1st and 7th days after ischemia, as well as histological and immunohistochemical assays in hippocampi. We showed in both protocols, depletions of DA and its metabolites (DOPAC and HVA), in the ischemic group, but these effects were reversed by curcumin. Additionally, a decrease seen in 5-HT contents, 1 day after ischemia, was also reversed by curcumin. This reversion was not seen 7 days later. On the other hand, a decrease observed in NE levels, at the 7th day, was totally reversed by curcumin. Furthermore, curcumin treatments increased neuronal viability and attenuated the immunoreactivity for COX-2 and TNF-alpha, in the hippocampus in both protocols. We showed that curcumin exerts neuroprotective actions, in a model of brain ischemia that are probably related to its anti-inflammatory activity