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This study explores the multifaceted influence of litter size, maternal care, exercise, and aging on rats' neurobehavioral plasticity and dentate gyrus microglia dynamics. Body weight evolution revealed a progressive increase until maturity, followed by a decline during aging, with larger litters exhibiting lower weights initially. Notably, exercised rats from smaller litters displayed higher body weights during the mature and aged stages. The dentate gyrus volumes showed no significant differences among groups, except for aged sedentary rats from smaller litters, which exhibited a reduction. Maternal care varied significantly based on litter size, with large litter dams showing lower frequencies of caregiving behaviors. Behavioral assays highlighted the detrimental impact of a sedentary lifestyle and reduced maternal care/large litters on spatial memory, mitigated by exercise in aged rats from smaller litters. The microglial dynamics in the layers of dentate gyrus revealed age-related changes modulated by litter size and exercise. Exercise interventions mitigated microgliosis associated with aging, particularly in aged rats. These findings underscore the complex interplay between early-life experiences, exercise, microglial dynamics, and neurobehavioral outcomes during aging.
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Herein, we report the synthesis and characterization of two Pt(II) coordination compounds, the new platinum(II)[N,N'-bis(salicylidene)-3,4-diaminobenzophenone)] ([Pt(sal-3,4-ben)]) and the already well-known platinum(II)[N,N'-bis(salicylidene)-o-phenylenediamine] ([Pt(salophen)]), along with their application as guests in a poly [9,9-dioctylfluorenyl-2,7-diyl] (PFO) conjugated polymer in all-solution processed single-layer white organic light-emitting diodes. Completely different performances were achieved: 2.2% and 15.3% of external quantum efficiencies; 2.8 cd A-1 and 12.1 cd A-1 of current efficiencies; and 3103 cd m-2 and 6224 cd m-2 of luminance for the [Pt(salophen)] and [Pt(sal-3,4-ben)] complexes, respectively. The Commission Internationale de l'Eclairage (CIE 1931) chromaticity color coordinates are (0.33, 0.33) for both 0.1% mol/mol Pt(II):PFO composites at between approximately 3.2 and 8 V. The optoelectronic properties of doped and neat PFO films have been investigated, using steady-state and time-resolved photoluminescence. Theoretical calculations at the level of relativistic density functional theory explained these results, based on the presence of the Pt(II) central ion's phosphorescence emission, considering spin-orbit coupling relationships. The overall results are explained, taking into account the active layer morphological properties, along with the device's electric balance and the emitter's efficiencies, according to deep-trap space-charge models. Considering the very simple structure of the device and the ease of synthesis of such compounds, the developed framework can offer a good trade-off for solution-deposited white organic light-emitting diodes (WOLEDs), with further applications in the field of lighting and signage.
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BACKGROUND/AIM: Certain constituents in migraine food triggers and non-steroidal anti-inflammatory drugs (NSAIDs) inhibit sulfotransferases (SULTs) that detoxify drugs/chemicals and play role in the metabolism of neurotransmitters. We aimed to dissect SULT1A1 modulation of CSD susceptibility and behavior in an in vivo experimental model using hesperidin, a SULT1A1 inhibitor found in citrus fruits (known migraine triggers) and mefenamic acid (SULT1A1 inhibitor), an NSAID to simulate medication overuse. METHODS: Hesperidin was used as SULT1A1 inhibitor found in citrus fruits, known migraine triggers and mefenamic acid (NSAID), another SULT1A1 inhibitor, was used to induce MO in rats. The groups were; 1) Hesperidin (ip) or its vehicle-DMSO (ip) 2) Chronic (4 weeks) mefenamic acid (ip) or its vehicle (ip) 3) Chronic mefenamic acid+hesperidin (ip) or DMSO (ip). CSD susceptibility was evaluated and behavioral testing was performed. SULT1A1 enzyme activity was measured in brain samples. RESULTS: Single-dose of hesperidin neither changed CSD susceptibility nor resulted in any behavioral change. Chronic mefenamic acid exposure resulted in increased CSD susceptibility, mechanical-thermal hypersensitivity, increased head shake, grooming and freezing and decreased locomotion. Single dose hesperidin administration after chronic mefenamic acid exposure resulted in increased CSD susceptibility and mechanical-thermal hypersensitivity, increased freezing and decreased locomotion. SULT1A1 enzyme activity was lower in mefenamic acid and mefenamic acid+hesperidin groups compared to their vehicles. CONCLUSION: Mefenamic acid and hesperidin have synergistic effect in modulating CSD susceptibility and pain behavior. Sulfotransferase inhibition may be the common mechanism by which food triggers and NSAIDs modulate migraine susceptibility. Further investigations regarding human provocation studies using hesperidin in migraine patients with medication overuse are needed.
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Ácido Mefenâmico , Transtornos de Enxaqueca , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Humanos , Ácido Mefenâmico/metabolismo , Ácido Mefenâmico/farmacologia , Ácido Mefenâmico/uso terapêutico , Transtornos de Enxaqueca/induzido quimicamente , Transtornos de Enxaqueca/tratamento farmacológico , Uso Excessivo de Medicamentos Prescritos , Ratos , Sulfotransferases/uso terapêuticoRESUMO
Spreading depression (SD) is an intense and prolonged depolarization in the central nervous systems from insect to man. It is implicated in neurological disorders such as migraine and brain injury. Here, using an in vivo mouse model of focal neocortical seizures, we show that SD may be a fundamental defense against seizures. Seizures induced by topical 4-aminopyridine, penicillin or bicuculline, or systemic kainic acid, culminated in SDs at a variable rate. Greater seizure power and area of recruitment predicted SD. Once triggered, SD immediately suppressed the seizure. Optogenetic or KCl-induced SDs had similar antiseizure effect sustained for more than 30 min. Conversely, pharmacologically inhibiting SD occurrence during a focal seizure facilitated seizure generalization. Altogether, our data indicate that seizures trigger SD, which then terminates the seizure and prevents its generalization.
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Depressão , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/metabolismo , 4-Aminopiridina , Animais , Bicuculina/farmacologia , Tronco Encefálico , Depressão Alastrante da Atividade Elétrica Cortical , Feminino , Técnicas de Introdução de Genes , Ácido Caínico/farmacologia , Masculino , Camundongos , Sistema Nervoso , Optogenética , Penicilinas/farmacologia , Bloqueadores dos Canais de Potássio/efeitos adversos , Convulsões/patologia , Tetrodotoxina/farmacologiaRESUMO
Graphene and its derivatives have emerged as potential materials for several technological applications including sunlight-driven water splitting reactions. This review critically addresses the latest achievements concerning the use of graphene as a player in the design of hybrid-photoelectrodes for photoelectrochemical cells. Insights about the charge carrier dynamics of graphene-based photocatalysts which include metal oxides and non-metal oxide semiconductors are also discussed. The concepts underpinning the continued progress in the field of graphene/photoelectrodes, including different graphene structures, architecture as well as the possible mechanisms for hydrogen and oxygen reactions are also presented. Despite several reports having demonstrated the potential of graphene-based photocatalysts, the achieved performance remains far from the targeted benchmark efficiency for commercial application. This review also highlights the challenges and opportunities related to graphene application in photoelectrochemical cells for future directions in the field.
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Cortical spreading depolarization (CSD) induces pro-inflammatory gene expression in brain tissue. However, previous studies assessing the relationship between CSD and inflammation have used invasive methods that directly trigger inflammation. To eliminate the injury confounder, we induced CSDs non-invasively through intact skull using optogenetics in Thy1-channelrhodopsin-2 transgenic mice. We corroborated our findings by minimally invasive KCl-induced CSDs through thinned skull. Six CSDs induced over 1 h dramatically increased cortical interleukin-1ß (IL-1ß), chemokine (C-C motif) ligand 2 (CCL2), and tumor necrosis factor-α (TNF-α) mRNA expression peaking around 1, 2 and 4 h, respectively. Interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) were only modestly elevated. A single CSD also increased IL-1ß, CCL2, and TNF-α, and revealed an ultra-early IL-1ß response within 10 min. The response was blunted in IL-1 receptor-1 knockout mice, implicating IL-1ß as an upstream mediator, and suppressed by dexamethasone, but not ibuprofen. CSD did not alter systemic inflammatory indices. In summary, this is the first report of pro-inflammatory gene expression after non-invasively induced CSDs. Altogether, our data provide novel insights into the role of CSD-induced neuroinflammation in migraine headache pathogenesis and have implications for the inflammatory processes in acute brain injury where numerous CSDs occur for days.
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Córtex Cerebral/fisiopatologia , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Inflamação/fisiopatologia , Animais , Feminino , Masculino , Camundongos , Camundongos TransgênicosRESUMO
Guanosine (GUO) is a guanine-based purine that has been extensively described in the literature as an endogenous nucleoside with participation in brain cell signalling pathways. Here, we evaluated whether chronic treatment with exogenous guanosine during brain development altered behavioral and electrophysiological parameters in adulthood. Rat pups received a daily intraperitoneal injection of 10, 50 or 100â¯mg/ kg/day GUO, or saline solution or no treatment (naive group) from postnatal (P) day 7 to P27. At P 60-65 the animals were behaviorally tested in the Elevated Plus-Maze (EPM). On P90-100, the electrophysiological phenomenon known as cortical spreading depression (CSD) was recorded on the right cortical surface for 4â¯h. With the EPM task, GUO treatment was associated with a significant increase in rearing behavior and a non-significant trend towards anxiogenic behavior. In a dose-dependent manner, GUO significantly (pâ¯<â¯0.01) increased weight gain on P90, and reduced the CSD propagation velocity from 3.42⯱â¯0.10 and 3.43⯱â¯0.10â¯mm/min in the Naive and Vehicle controls, respectively, to 3.05⯱â¯0.12â¯mm/min, 2.87⯱â¯0.07â¯mm/min and 2.25⯱â¯0.25â¯mm/min in the groups treated with 10, 50 and 100â¯mg/kg/d GUO, respectively. The results confirmed the hypothesis that the chronic treatment with GUO early in life modulates CSD and body weight. Data on CSD propagation suggest that, besides its suppressing action on glutamatergic transmission (via enhancement of astrocytic glutamate uptake), GUO might act as an antioxidant in the brain, a hypothesis that deserves further exploration.
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Depressão Alastrante da Atividade Elétrica Cortical/efeitos dos fármacos , Guanosina/farmacologia , Animais , Ansiedade/metabolismo , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Encéfalo/metabolismo , Córtex Cerebral/metabolismo , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVES: To evaluate how safflower oil (SFO) influences brain electrophysiology and cortical oxidative status in the offspring, mothers received a diet with SFO during brain development period. METHODS: Beginning on the 14th day of gestation and throughout lactation, rats received safflower (safflower group - SG) or soybean oil (control group - CG) in their diet. At 65 days old, cortical spreading depression (CSD) and cortex oxidative status were analyzed in the offspring. RESULTS: SG presented reduction of the CSD velocity as compared to the CG (SG: 3.24 ± 0.09; CG: 3.37 ± 0.07â mm/min). SFO reduced levels of lipid peroxidation by 39.4%. SG showed the following increases: glutathione-S-transferase, 40.8% and reduced glutathione, 34.3%. However, SFO decreased superoxide dismutase by 40.4% and catalase by 64.1%. To control for interhemispheric effects, since CSD was recorded only in the right cortex, we evaluated the oxidative status in both sides of the cortex; no differences were observed. DISCUSSION: Data show that when SFO is consumed by the female rats during pregnancy and lactation, the offspring present long-term effects on brain electrophysiology and cortical oxidative state. The present study highlights the relevance of understanding the SFO intake of pregnant and lactating mammals.
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Encéfalo/efeitos dos fármacos , Carthamus tinctorius/química , Lactação , Óleo de Cártamo/farmacologia , Animais , Encéfalo/metabolismo , Catalase/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Depressão Alastrante da Atividade Elétrica Cortical/efeitos dos fármacos , Feminino , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Vagus nerve stimulation has recently been reported to improve symptoms of migraine. Cortical spreading depression is the electrophysiological event underlying migraine aura and is a trigger for headache. We tested whether vagus nerve stimulation inhibits cortical spreading depression to explain its antimigraine effect. Unilateral vagus nerve stimulation was delivered either noninvasively through the skin or directly by electrodes placed around the nerve. Systemic physiology was monitored throughout the study. Both noninvasive transcutaneous and invasive direct vagus nerve stimulations significantly suppressed spreading depression susceptibility in the occipital cortex in rats. The electrical stimulation threshold to evoke a spreading depression was elevated by more than 2-fold, the frequency of spreading depressions during continuous topical 1 M KCl was reduced by â¼40%, and propagation speed of spreading depression was reduced by â¼15%. This effect developed within 30 minutes after vagus nerve stimulation and persisted for more than 3 hours. Noninvasive transcutaneous vagus nerve stimulation was as efficacious as direct invasive vagus nerve stimulation, and the efficacy did not differ between the ipsilateral and contralateral hemispheres. Our findings provide a potential mechanism by which vagus nerve stimulation may be efficacious in migraine and suggest that susceptibility to spreading depression is a suitable platform to optimize its efficacy.
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Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Transtornos de Enxaqueca/fisiopatologia , Estimulação do Nervo Vago , Animais , Encéfalo/fisiologia , Estimulação Elétrica , Masculino , Modelos Animais , Ratos Sprague-DawleyRESUMO
The use of dexamethasone (Dex) to treat chronic lung disease in preterm infants may produce adverse effects in the developing brain. Here, we evaluated the effects of neonatal Dex on the propagation of cortical spreading depression (CSD), and tested the action of vitamins C and E against the effect of Dex. Five groups of Wistar rats received, respectively: [1] no treatment (Naïve); [2] Vehicle (V); [3] tapering doses of Dex (Dex; 0.5mg/kg, 0.3mg/kg, and 0.1mg/kg) on postnatal day (PND) 1-3; [4] Dex plus 200mg/kg vitamin C and 100mg/kg vitamin E (DexCE); [5] only vitamins C and E (CE). Vehicle and vitamins were administered on PND 1-6. CSD was recorded after the pups reached maturity (PND 60-70). The Dex-treated group presented with higher CSD velocities (mean values ± SD, in mm/min: 4.14 ± 0.22, n=10) compared with the control groups (Naïve: 3.52 ± 0.13, n=8; V: 3.57 ± 0.18, n=10; CE: 3.51 ± 0.24, n=10; p<0.05 for all). Vitamins C and E antagonized this effect (DexCE group; CSD velocity: 3.43 ± 0.12, n=9). No intergroup difference was observed concerning P-wave amplitude and duration. In all groups, after the cortex underwent CSD, the electrocorticogram (ECoG) amplitude increased approximately 50% compared with the baseline amplitude for the same animal (CSD-induced ECoG potentiation); however, no intergroup difference was observed. Data suggest that coadministration of antioxidant vitamins with Dex may be a helpful therapeutic strategy to reduce brain adverse effects of dexamethasone.
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Antioxidantes/farmacologia , Córtex Cerebral/efeitos dos fármacos , Depressão Alastrante da Atividade Elétrica Cortical/efeitos dos fármacos , Depressão/induzido quimicamente , Dexametasona/toxicidade , Vitaminas/farmacologia , Animais , Animais Recém-Nascidos , Depressão/tratamento farmacológico , Glucocorticoides/farmacologia , Masculino , Ratos WistarRESUMO
Although ascorbic acid (AA) is an antioxidant, under certain conditions it can facilitate oxidation, which may underlie the opposite actions of AA on brain excitability in distinct seizure models. Here, we investigated whether chronic AA administration during brain development alters cortical excitability as a function of AA dose, as indexed by cortical spreading depression (CSD) and by the levels of lipid peroxidation-induced malondialdehyde. Well-nourished and early-malnourished rats received per gavage 30, 60, or 120 mg/kg/d of AA, saline, or no gavage treatment (naïve group) at postnatal days 7-28. CSD propagation and malondialdehyde levels were analyzed at 30-40 days. Confirming previous observations, CSD velocities were significantly higher in the early-malnourished groups than in the well-nourished groups. AA dose was important: 30 mg/kg/d AA decelerated CSD and reduced malondialdehyde levels, whereas 60 mg/kg/d and 120 mg/kg/d accelerated CSD and augmented malondialdehyde levels compared with the corresponding saline and naïve groups. Our findings reinforce previous suggestion that AA acts as an antioxidant in the brain when administered at low doses, but as a prooxidant at high doses, as indicated by CSD propagation and malondialdehyde levels.
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Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Desnutrição/fisiopatologia , Oxidantes/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Encéfalo/crescimento & desenvolvimento , Depressão Alastrante da Atividade Elétrica Cortical/efeitos dos fármacos , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Relação Dose-Resposta a Droga , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Malondialdeído/metabolismo , Distribuição Aleatória , Ratos WistarRESUMO
A silica-cerium mixed oxide (SiCe) was prepared by the sol-gel process, using tetraethylorthosilicate and cerium nitrate as precursors and obtained as an amorphous solid possessing a specific surface area of 459 m(2) g(-1). Infrared spectroscopy of the SiCe material showed the formation of the Si-O-Ce linkage in the mixed oxide. Scanning electron microscopy/energy dispersive spectroscopy indicated that the cerium oxide particles were homogenously dispersed on the matrix surface. X-ray diffraction and (29)Si solid-state nuclear magnetic resonance implied non-crystalline silica matrices with chemical environments that are typical for silica-based mixed oxides. X-ray photoelectron spectroscopy showed that Ce was present in approximately equal amounts of both the 3+ and 4+ oxidation states. Cyclic voltammetry data of electrode prepared from the silica-cerium mixed oxide showed a peak for oxidation of Ce(3+)/Ce(4+) at 0.76 V and electrochemical impedance spectroscopy equivalent circuit indicated a porous structure with low charge transfer resistance. In the presence of nitrite, the SiCe electrode shows an anodic oxidation peak at 0.76 V with a linear response as the concentration of the analyte increases from 3×10(-5) at 3.9×10(-3) mol L(-1).