Exendin-4 Prevents Memory Loss and Neuronal Death in Rats with Sporadic Alzheimer-Like Disease.

This study investigated the neuroprotective effects of exendin-4 (EXE-4), an analog of the glucagon-like peptide 1 receptor (GLP-1R) on memory and on the neuronal populations that constitute the hippocampus of rats submitted to a sporadic dementia of Alzheimer's type (SDAT). Male Wistar rats received streptozotocin (STZ icv, 3 mg/kg diluted in aCFS, 5 µl/ventricle) and were treated for 21 days with EXE-4 (10 µg/kg, ip; saline as the vehicle). Four groups were formed: vehicle, EXE-4, STZ, and STZ + EXE-4. The groups were submitted to Y-Maze (YM), object recognition (ORT), and object displacement tasks (ODT) to assess learning and memory. The brains were used for immunohistochemical and immunofluorescent techniques with antibodies to NeuN, cleaved caspase-3 (CC3), PCNA, doublecortin (DCX), synaptophysin (SYP), and insulin receptor (IR). STZ worsened spatial memory in the YMT, as well as short-term (STM) and long-term (LTM) memories in the ORT and ODT, respectively. EXE-4 protected against memory impairment in STZ animals. STZ reduced mature neuron density (NeuN) and increased cell apoptosis (CC3) in the DG, CA1, and CA3. EXE-4 protected against neuronal death in all regions. EXE-4 increased PCNA+ cells in all regions of the hippocampus, and STZ attenuated this effect. STZ reduced neurogenesis in DG per se as well as synaptogenesis induced by EXE-4. EXE-4 increased immunoreactivity to IR in the CA1. From these findings, EXE-4 showed a beneficial effect on hippocampal pyramidal and granular neurons in the SDAT showing anti-apoptotic properties and promoting cell proliferation. In parallel, EXE-4 preserved the memory of SDAT rats. EXE-4 appears to enhance synapses at CA3 and DG. In conclusion, these data indicate that agonists to GLP-1R have a beneficial effect on hippocampal neurons in AD.

Neuroprotection elicited by taurine in sporadic Alzheimer-like disease: benefits on memory and control of neuroinflammation in the hippocampus of rats.

This study aimed to analyze whether taurine has a nootropic effect on short-term and long-term memory in a model of sporadic dementia of the Alzheimer's type (SDAT). Moreover, we evaluated the immunoreactivity and insulin receptor (IR) distribution and markers for neurons and glial cells in the hippocampus of rats with SDAT and treated with taurine. For this, Male Wistar rats received STZ (ICV, 3 mg/kg, bilateral, 5ul per site, aCFS vehicle) and were treated with taurine (100 mg/kg orally, 1 time per day, saline vehicle) for 25 days. The animals were divided into 4 groups: vehicle (VE), taurine (TAU), ICV-STZ (STZ) and ICV-STZ plus taurine (STZ + TAU). At the end of taurine treatment, short- and long-term memory were assessed by performance on object recognition and Y-maze tasks. Insulin receptor (IR) was evaluated by immunoperoxidase while mature neurons (NeuN), astrocytes (GFAP, S100B, SOX9), and microglia (Iba-1) were evaluated by immunofluorescence. STZ induced worse spatial and recognition memory (INDEX) in YM and ORT tasks. Taurine protected against STZ-induced memory impairment. SDAT reduced the population of mature neurons as well as increased astrocytic and microglial reactivity, and taurine protected against these STZ-induced effects, mainly in the CA1 region of the hippocampus. Taurine increases IR expression in the hippocampus, and protects against the reduction in the density of this receptor in CA1 induced by STZ. In conclusion, these findings demonstrate that taurine is able to enhance memory, up-regulates IR in the hippocampus, protects the neuron population, and reduces the astrogliosis found in SDAT.

Effects of tannic acid in streptozotocin-induced sporadic Alzheimer's Disease: insights into memory, redox status, Na+, K+-ATPase and acetylcholinesterase activity.

The aim of this study was to investigate the ability of tannic acid (TA) in preventing memory deficits and neurochemical alterations observed in a model for Sporadic Dementia of Alzheimer's Type. Rats were treated with TA (30 mg/kg) daily for 21 days, and subsequently received intracerebroventricular injection of streptozotocin (STZ). We observed that STZ induced learning and memory impairments; however, treatment with TA was able to prevent these effects. In cerebral cortex and hippocampus, STZ induced an increase in acetylcholinesterase activity, reduced Na+, K+-ATPase activity and induced oxidative stress increasing thiobarbituric acid-reactive substances, nitrites and reactive oxygen species levels and reducing the activity of antioxidant enzymes. Treatment with TA was able in prevent the major of these neurochemical alterations. In conclusion, TA prevented memory deficits, alterations in brain enzyme activities, and oxidative damage induced by STZ. Thus, TA can be an interesting strategy in the prevention of Sporadic Alzheimer's Disease.

Protective Effects of Inosine on Memory Consolidation in a Rat Model of Scopolamine-Induced Cognitive Impairment: Involvement of Cholinergic Signaling, Redox Status, and Ion Pump Activities.

This study investigated the effects of inosine on memory acquisition and consolidation, cholinesterases activities, redox status and Na+, K+-ATPase activity in a rat model of scopolamine-induced cognitive impairment. Adult male rats were divided into four groups: control (saline), scopolamine (1 mg/kg), scopolamine plus inosine (50 mg/kg), and scopolamine plus inosine (100 mg/kg). Inosine was pre-administered for 7 days, intraperitoneally. On day 8, scopolamine was administered pre (memory acquisition protocol) or post training (memory consolidation protocol) on inhibitory avoidance tasks. The animals were subjected to the step-down inhibitory avoidance task 24 hours after the training. Scopolamine induced impairment in the acquisition and consolidation phases; however, inosine was able to prevent only the impairment in memory consolidation. Also, scopolamine increased the activity of acetylcholinesterase and reduced the activity of Na+, K+-ATPase and the treatment with inosine protected against these alterations in consolidation protocol. In the animals treated with scopolamine, inosine improved the redox status by reducing the levels of reactive oxygen species and thiobarbituric acid reactive substances and restoring the activity of the antioxidant enzymes, superoxide dismutase and catalase. Our findings suggest that inosine may offer protection against scopolamine-induced memory consolidation impairment by modulating brain redox status, cholinergic signaling and ion pump activity. This compound may provide an interesting approach in pharmacotherapy and as a prophylactic against neurodegenerative mechanisms involved in Alzheimer's disease.

Investigating the Effect of Inosine on Brain Purinergic Receptors and Neurotrophic and Neuroinflammatory Parameters in an Experimental Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative pathology characterized by progressive impairment of memory, associated with neurochemical alterations and limited therapy. The aim of this study was to evaluate the effects of inosine on memory, neuroinflammatory cytokines, neurotrophic factors, expression of purinergic receptors, and morphological changes in the hippocampus and cerebral cortex of the rats with AD induced by streptozotocin (STZ). Male rats were divided into four groups: I, control; II, STZ; III, STZ plus inosine (50 mg/kg); and IV, STZ plus inosine (100 mg/kg). The animals received intracerebroventricular injections of STZ or buffer. Three days after the surgical procedure, animals were treated with inosine (50 mg/kg or 100 mg/kg) for 25 days. Inosine was able to prevent memory deficits and decreased the immunoreactivity of the brain A2A adenosine receptor induced by STZ. Inosine also increased the levels of brain anti-inflammatory cytokines (IL-4 and IL-10) and the expression of brain-derived neurotrophic factor and its receptor. Changes induced by STZ in the molecular layer of the hippocampus were attenuated by treatment with inosine. Inosine also protected against the reduction of immunoreactivity for synaptophysin induced by STZ in CA3 hippocampus region. However, inosine did not prevent the increase in GFAP in animals exposed to STZ. In conclusion, our findings suggest that inosine has therapeutic potential for AD through the modulation of different brain mechanisms involved in neuroprotection.

Neuroprotective Effect of Taurine against Cell Death, Glial Changes, and Neuronal Loss in the Cerebellum of Rats Exposed to Chronic-Recurrent Neuroinflammation Induced by LPS.

The present study investigated the neuroprotective effect of taurine against the deleterious effects of chronic-recurrent neuroinflammation induced by LPS in the cerebellum of rats. Adult male Wistar rats were treated with taurine for 28 days. Taurine was administered at a dose of 30 or 100 mg/kg, by gavage. On days 7, 14, 21, and 28, the animals received LPS (250 µg/kg) intraperitoneally. The vehicle used was saline. The animals were divided into six groups: vehicle, taurine 30 mg/kg, taurine 100 mg/kg, LPS, LPS plus taurine 30 mg/kg, and LPS plus taurine 100 mg/kg. On day 29, the animals were euthanized, and the cerebellum was removed and prepared for immunofluorescence analysis using antibodies of GFAP, NeuN, CD11b, and cleaved caspase-3. LPS group showed a reduction in the immunoreactivity of GFAP in the arbor vitae and medullary center and of NeuN in the granular layer of the cerebellar cortex. LPS increased the immunoreactivity of CD11b in the arbor vitae and in the medullary center. Taurine protected against these effects induced by LPS in immunoreactivity of GFAP, NeuN, and CD11b, with the 100 mg/kg dose being the most effective. LPS induced an increase in the number of positive cleaved caspase-3 cells in the Purkinje cell layers, granular layer, arbor vitae, and medullary center. Taurine showed its antiapoptotic activity by reducing the cleaved caspase-3 cells in relation to the LPS group. Here, a potential neuroprotective role of taurine can be seen since this amino acid was effective in protecting the cerebellum of rats against cell death and changes in glial and neuronal cells in the face of chronic-recurrent neuroinflammation.

Effect of QTC-4-MeOBnE Treatment on Memory, Neurodegeneration, and Neurogenesis in a Streptozotocin-Induced Mouse Model of Alzheimer's Disease.

Growing evidence suggests that drugs targeting neurogenesis and myelinization could be novel therapeutic targets against Alzheimer's disease (AD). Intracerebroventricular (icv) injection of streptozotocin (STZ) induces neurodegeneration through multiple mechanisms ultimately resulting in reduced adult neurogenesis. Previously, the multitarget compound QTC-4-MeOBnE (1-(7-chloroquinolin-4-yl)-N-(4-methoxybenzyl)-5-methyl-1H-1,2,3-triazole-4-carboxamide) demonstrated beneficial effects in preclinical models of AD. Here we investigated its pharmacokinetics profile and the effect on memory impairments and neurodegeneration induced by STZ. Two icv injections of STZ resulted in significant cognitive and memory impairments, assessed by novel object recognition, Y-maze, social recognition, and step-down passive avoidance paradigms. These deficits were reversed in STZ-injected mice treated with QTC-4-MeOBnE. This effect was associated with reversion of neuronal loss in hippocampal dentate gyrus, reduced oxidative stress, and amelioration of synaptic function trough Na+/K+ ATPase and acetylcholinesterase activities. Furthermore, brains from QTC-4-MeOBnE-treated mice had a significant increase in adult neurogenesis and remyelination through Prox1/NeuroD1 and Wnt/ß-catenin pathways. Overall, our findings support the potential anti-AD effect of QTC-4-MeOBnE through multiple pathways, all of which have been involved in the onset and progression of the disease.

Impacts of dose and length of exposure to boldenone and stanazolol on enzymatic antioxidant systems, myeloperoxidase and NAGase activities, and glycogen and lactate levels in rat liver.

We investigated the adverse effects of the anabolic androgenic steroids (AAS) boldenone (BOL) and stanazolol (ST) on the enzymatic antioxidant systems of the rat liver. Male Wistar rats were divided in three protocols (P): PI, 5 mg/kg BOL or ST once a week for 4 weeks; PII, 2.5 mg/kg BOL or ST once a week for 8 weeks; PIII, 1.25 mg/kg BOL or ST once a week for 12 weeks. AAS were administered intramuscularly (0.2 ml, olive oil vehicle) once a week in all protocols. Activities of the enzymes glutathione peroxidase (GPx), glutathione S-transferase (GST), and glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), were investigated. We assessed the content of hydrogen peroxide (H2O2), glycogen and lactate; and enzyme markers of neutrophils (myeloperoxidase, MPO) and macrophages (NAGase). PI and PII altered the SOD and CAT activities and increased the H2O2 content. PI led to increases in the MPO and NAGase activities. In contrast, changes in GPx, GST and, GR were observed under PII and, to a greater extend, under PIII. Following PIII, GPx, GR, and GST exhibited reduced activities. All protocols altered the glycogen and lactate content. The use of high doses of AAS for a short duration first alters SOD/CAT activity. In contrast, at lower doses of AAS for long periods is associated with changes in the glutathione system. Protocols with high doses of AAS for a short duration exert the most deleterious effects on redox status, markers of cellular infiltration, and the metabolic functioning of hepatic tissues.

Aluminum-induced alterations of purinergic signalling in embryonic neural progenitor cells.

The ubiquitous presence of aluminum in the environment leads to a high likelihood of human exposure. Neurotoxicity of the trivalent cationic form of this metal (Al3+) occurs in the central nervous system via accumulation of Al in cells of neural origin, including neural progenitor cells (NPCs). NPCs play a key role in the development and regeneration of the brain throughout life; therefore, this metal may contribute to neuropathological conditions. Here, we evaluated the effects of different Al3+ concentrations (0-50 µM) on the purinergic system of NPCs isolated from embryonic telencephalons, cultured as neurospheres. Al3+ adhered to the cell surface of neurospheres reducing extracellular ATP release, as well as ATP, ADP, and AMP hydrolysis by NTPDase and 5'-nucleotidase, respectively. In addition, impaired nucleotide release by Al3+ reduced P2Y1 and adenosine A2A receptors expression in differentiated neurospheres. These receptors are crucial for NPC proliferation during brain development and self-repair against external stimuli, such as metal exposure. Thus, Al3+ represents an environmental agent linked to neurodegeneration through alterations in the ATP-signalling pathway, proving to be a potential mechanism associated with NPC proliferation and brain degeneration.

Inosine protects against impairment of memory induced by experimental model of Alzheimer disease: a nucleoside with multitarget brain actions.

RATIONALE: Inosine is a naturally occurring purine nucleoside formed by adenosine breakdown. This nucleoside is reported to exert potent effects on memory and learning, possibly through its antioxidant and anti-inflammatory actions. OBJECTIVE: The objective is to evaluate the effects of inosine on the behavioral and neurochemical parameters in a rat model of Alzheimer's disease (AD) induced by streptozotocin (STZ). METHODS: Adult male rats were divided into four groups: control (saline), STZ, STZ plus inosine (50 mg/kg), and STZ plus inosine (100 mg/kg). STZ (3 mg/kg) was administered by bilateral intracerebroventricular injection. The animals were treated intraperitoneally with inosine for 25 days. Memory, oxidative stress, ion pump activities, acetylcholinesterase (AChE), and choline acetyltransferase (ChAT) activities and expression were evaluated in the cerebral cortex and hippocampus. RESULTS: The memory impairment induced by STZ was prevented by inosine. An increase in the Na+, K+-ATPase, and Mg-ATPase activities and a decrease in the Ca2+-ATPase activity were induced by STZ in the hippocampus and cerebral cortex, and inosine could prevent these alterations in ion pump activities. Inosine also prevented the increase in AChE activity and the alterations in AChE and ChAT expression induced by STZ. STZ increased the reactive oxygen species, nitrite levels, and superoxide dismutase activity and decreased the catalase and glutathione peroxidase activities. Inosine treatment conferred protection from these oxidative alterations in the brain. CONCLUSIONS: Our findings demonstrate that inosine affects brain multiple targets suggesting that this molecule may have therapeutic potential against cognitive deficit and tissue damage in AD.

ADA activity is decreased in lymphocytes from patients with advanced stage of lung cancer.

Cigarette smoking is directly associated with lung cancer. Non-small cell lung carcinoma (NSCLC) represents approximately 80% from all types of lung cancer. This latter is hard to diagnose and to treat due to the lack of symptoms in early stages of the disease. The aim of this study was to evaluate ADA activity and the expression of P2X7, A1, and A2A receptors and in lymphocytes. In addition, the profile of pro-inflammatory and anti-inflammatory cytokines serum levels of patients with lung cancer in advanced stage was evaluated. Patients (n = 13) previously treated for lung cancer at stage IV (UICC) with chemotherapy had their blood collected. Cancer patients showed a decrease in ADA activity and an increase in A1 receptor expression in lymphocytes when compared to the control group. Moreover, patients exhibited an increase in IL-6 and TNF-α, while IL-17 and INF-ϒ serum levels were lower in patients with lung cancer. The decreased ADA activity and the increase in A1 receptor expression may contribute to adenosine pro-tumor effects by increasing IL-6 and TNF-α and decreasing IL-17 and INF-γ serum levels. Our data show an indirect evidence that purinergic signaling may have a role in promoting a profile of cytokines levels that favors tumor progression.

Aluminum affects neural phenotype determination of embryonic neural progenitor cells.

Aluminum (Al) is a neurotoxin and is associated with the etiology of neurodegenerative diseases, such as Alzheimer's disease (AD). The Al-free ion (Al3+) is the biologically reactive and toxic form. However, the underlying mechanisms of Al toxicity in the brain remain unclear. Here, we evaluated the effects of Al3+ (in the chloride form-AlCl3) at different concentrations (0.1-100 µM) on the morphology, proliferation, apoptosis, migration and differentiation of neural progenitor cells (NPCs) isolated from embryonic telencephalons, cultured as neurospheres. Our results reveal that Al3+ at 100 µM reduced the number and diameter of neurospheres. Cell cycle analysis showed that Al3+ had a decisive function in proliferation inhibition of NPCs during neural differentiation and induced apoptosis on neurospheres. In addition, 1 µM Al3+ resulted in deleterious effects on neural phenotype determination. Flow cytometry and immunocytochemistry analysis showed that Al3+ promoted a decrease in immature neuronal marker ß3-tubulin expression and an increase in co-expression of the NPC marker nestin and glial fibrillary acidic protein. Thus, our findings indicate that Al3+ caused cellular damage and reduced proliferation and migration, resulting in global inhibition of NPC differentiation and neurogenesis.

Laser Photobiomodulation in the acute inflammatory response of the calcaneal tendon injury in rats exposed to cigarette smoke / Fotobiomodulação Laser na resposta inflamatória aguda em lesão do tendão calcâneo em ratos expostos a fumaça de cigarro / Fotobiomodulación láser en la respuesta inflamatoria aguda en lesión del tendón calcáneo en ratones expuestos a humo de cigarrillo

ABSTRACT Nicotine delays the healing process and increases the levels of myeloperoxidase (MPO), an enzyme that plays a key role in the production of reactive oxygen species during the inflammatory process. Laser Photobiomodulation (PBM) is one of the most used electrophysical agents in the treatment of the calcaneal tendon, however, its effects on MPO activity need to be further elucidated. This study aimed to evaluate the effects of laser PBM on MPO activity after inflicting an injury to the calcaneal tendon of rats exposed to cigarette smoke. Thirty-four male Wistar rats with 90 days of age were used. After 14 days of exposure to cigarette smoke, the animals were divided into three experimental groups: control group (CG, n=12), not submitted to injury or treatment; sham group (ShG, n=10), submitted to partial calcaneal tendon injury and laser PBM simulation; and laser PBM group (PBMG, n=12), submitted to partial calcaneal tendon lesion and treated with laser PBM within the first minute after injury. PBM decreased MPO activity levels in PBMG compared to ShG (CG: 1.38±0.69pg/ml; ShG: 3.78±1.09pg/ml; PBMG: 2.58±0.93pg/ml; p<0.005). In conclusion, applying laser PBM immediately after inflicting damage to the calcaneal tendon attenuates acute inflammatory activity in rats exposed to cigarette smoke.

RESUMO A nicotina retarda o processo de cicatrização e eleva os níveis da enzima mieloperoxidase (MPO), a qual possui um papel fundamental na produção de espécies reativas de oxigênio durante o processo inflamatório. A fotobiomodulação laser (FBM) é um dos agentes eletrofísicos mais utilizados no tratamento do tendão calcâneo, no entanto, os seus efeitos sobre a atividade da MPO carecem de maior elucidação. Este estudo objetivou avaliar os efeitos da FBM sobre a atividade da MPO, após lesão do tendão calcâneo em ratos expostos à fumaça de cigarro. Foram utilizados 34 ratos Wistar, machos, com 90 dias de vida. Após 14 dias de exposição à fumaça de cigarro, os animais foram divididos em três grupos experimentais: grupo controle (GC, n=12), não submetido à lesão ou tratamento; grupo sham (GSh, n=10), submetido à lesão parcial do tendão calcâneo e a simulação da FBM laser; grupo FBM laser (GFBM, n=12), submetido à lesão parcial do tendão calcâneo e tratados com FBM laser, no primeiro minuto após a lesão. A FBM diminuiu os níveis de atividade da MPO no GFBM em comparação ao GSh (GC: 1,38±0,69 pg/ml; GSh: 3,78±1,09pg/ml; GFBM: 2,58±0,93pg/ml; p<0,005). Conclui-se que a FBM laser aplicada imediatamente após lesão do tendão calcâneo, atenua a atividade inflamatória aguda em ratos expostos à fumaça de cigarro.

RESUMEN La nicotina retarda el proceso de cicatrización y eleva los niveles de la enzima mieloperoxidasa (MPO), que tiene un papel fundamental en la producción de especies reactivas de oxígeno durante el proceso inflamatorio. La fotobiomodulación con láser (FBM) es uno de los agentes electrofísicos más utilizados en el tratamiento del tendón calcáneo, sin embargo sus efectos sobre la actividad de la MPO carecen de mayor elucidación. Este estudio objetivó evaluar los efectos de la FBM sobre la actividad de la MPO después de lesión del tendón calcáneo en ratones expuestos al humo de cigarrillo. Se utilizaron 34 ratones Wistar, machos, con 90 días de vida. Después de 14 días de exposición al humo de cigarrillo, los animales fueron divididos en tres grupos experimentales: grupo de control (GC, n=12), no sometido a la lesión o tratamiento; grupo sham (GSh, n=10), sometido a la lesión parcial del tendón calcáneo y a la simulación de la FBM láser; y el grupo FBM láser (GFBM, n=12), sometido a la lesión parcial del tendón calcáneo y tratado con FBM láser, en el primer minuto después de la lesión. La FBM disminuyó los niveles de actividad de MPO en el GFBM en comparación con el GSh (GC: 1,38±0,69 pg/ml; GSh: 3,78±1,09pg/ml; GFBM: 2,58±0,93pg/ml, p<0,005). Se concluye que la FBM láser aplicada inmediatamente después de la lesión del tendón calcáneo atenúa la actividad inflamatoria aguda en ratones expuestos al humo de cigarrillo.

Protection of cholinergic and antioxidant system contributes to the effect of Vitamin D3 ameliorating memory dysfunction in sporadic dementia of Alzheimer's type.

OBJECTIVE: Investigate Vitamin D3 (VD3) effect on the Acetylcholinesterase (AChE), oxidative damage and behavioral tests in animals subjected to Intracerebroventicular injection of Streptozotocin (ICV-STZ) simulating a Sporadic Dementia of Alzheimer's Type (SDAT) and treated with VD3 (21 days). METHODS: Animals were divided into eight groups: Vehicle, VD12.5 µg/kg, VD42 µg/kg, VD125 µg/kg, STZ, STZ+VD12.5 µg/kg, STZ+VD42 µg/kg, STZ+VD125 µg/kg. RESULTS: VD3 prevented the increase in AChE in groups of VD42 µg/kg and VD125 µg/kg; in AChE of synaptossomes and TBARS levels prevented the increase in group VD125 µg/kg; in ROS levels there was not a significant difference; for the Carbonyl Content all doses prevented the increase. Total Thiols prevent the decrease in VD42 µg/kg and VD125 µg/kg, and Reduced Glutathione prevented the decrease in VD125 µg/kg, Oxidized Glutathione prevented the increase in VD125 µg/kg. In relation to behavioral tests, the VD3 prevented the increase in time to find (days 2 and 3), in the time to find the platform (day 3) and in time spent in the quadrant (day 2). However, in relation to crossings there was not difference in groups. These results indicated the therapeutic effect of the VD3 in model of STZ in rats.

Effects of Scalp Acupuncture on Functional Deficits Induced by Early Sensorimotor Restriction.

The aim of this study was to investigate the effects of scalp acupuncture and electrostimulation, combined or not, in a disuse model consisted of early sensorimotor restriction in rats. Male Wistar pups received sensorimotor restriction from the second postnatal day (P2) until P28. Animals were divided into five different groups (n = 6): control (CT), sensorimotor restricted (SR), acupuncture (AC), electrostimulation (EL), and electroacupuncture (AC+EL). Experimental animals received sham, acupuncture, or electrical stimulation, combined or not, of two scalp regions for 7 days (P29-P35). Before treatment period (P29) and after treatment (P36), animals were evaluated with the narrow suspended bar, horizontal ladder, and stride length tests. SR animals had worse performance in the narrow suspended and horizontal ladder tasks compared with SR animals at P29 (p ≤ 0.005). Significant improvements were observed in both tasks in AC, EL, and EL+AC groups comparing P29 and P36 (p < 0.001). Also, at P35, all treated animals performed significantly better motor tasks compared with SR group (p < 0.05). There was no difference between treated groups. Finally, acupuncture and electrical stimulation, combined or not, have beneficial effect on motor performance following early developmental disuse.

A phytochemical study of the Cuphea glutinosa from Southern Brazil: Na+,K+-ATPase activity inhibition and antioxidant properties.

This study investigated the antioxidant activity of Cuphea glutinosa (CG) and its effect on Na+, K+-ATPase from cardiac muscle. The ethanolic extract showed higher antioxidant capacity compared to aqueous and ethyl acetate fraction. Ethyl acetate fraction showed ß-sitosterol-3-O-ß-glucoside, kaempferol, quercetin, isoquercetin, gallic acid methyl ester, and gallic acid. The ethanolic extract also reduced the Na+,K+-ATPase activity. CG presented a promising antioxidant activity and inhibitory effect on the Na+, K+-ATPase activity, supporting biochemical evidences the popular use of this plant in the treatment of heart failure.

Physical exercise prevents memory impairment in an animal model of hypertension through modulation of CD39 and CD73 activities and A2A receptor expression.

: Background: Central nervous system function has been emerging as an approach to understand hypertension-mediated memory dysfunction, and chronic exercise is able to modulate the purinergic system. METHOD: Herein, we investigated the effect of chronic swimming training on the purinergic system in cortex and hippocampus of L-NAME-induced hypertensive rats. Male Wistar rats were divided into four groups: Control, Exercise, L-NAME and Exercise L-NAME. Inhibitory avoidance test was used to assess memory status. NTPDase, CD73 and adenosine deaminase activities and expression, and P2 receptors expression were analyzed. Data were analyzed using two-way ANOVA and Kruskal-Wallis tests, considering P less than 0.05. RESULTS: Physical exercise reduced the blood pressure and prevented memory impairment induced by L-NAME model of hypertension. L-NAME treatment promoted an increase in NTPDase1, NTPDase3 and CD73 expression and activity in the cortex. A2A expression is increased in hippocampus and cortex in the hypertension group and exercise prevented this overexpression. CONCLUSION: These changes suggest that hypertension increases adenosine generation, which acts through A2A receptors, and exercise prevents these effects. These data may indicate a possible mechanism by which exercise may prevent memory impairment induced by L-NAME.

Caffeine and high intensity exercise: Impact on purinergic and cholinergic signalling in lymphocytes and on cytokine levels.

This study evaluated the effects of caffeine in combination with high-intensity interval training (HIIT) on sensitivity to glucocorticoids and proliferation of lymphocytes, IL-6 and IL-10 levels and NTPDase, adenosine deaminase (ADA) and acetylcholinesterase (AChE) activity in rat lymphocytes. The animals were divided into groups: control, caffeine 4 mg/kg, caffeine 8 mg/kg, HIIT, HIIT plus caffeine 4 mg/kg and HIIT plus caffeine 8 mg/kg. The rats were trained three times a week for 6 weeks for a total workload 23% of body weight at the end of the experiment. Caffeine was administered orally 30 min before the training session. When lymphocytes were stimulated with phytohaemagglutinin no changes were observed in proliferative response between trained and sedentary animals; however, when caffeine was associated with HIIT an increase in T lymphocyte proliferation and in the sensitivity of lymphocytes to glucocorticoids occurred. ATP and ADP hydrolysis was decreased in the lymphocytes of the animals only trained and caffeine treatment prevented alterations in ATP hydrolysis. HIIT caused an increase in the ADA and AChE activity in lymphocytes and this effect was more pronounced in rats trained and supplemented with caffeine. The level of IL-6 was increased while the level of IL-10 was decreased in trained animals (HIIT) and caffeine was capable of preventing this exercise effect. Our findings suggest that caffeine ingestion attenuates, as least in part, the immune and inflammatory alterations following a prolonged HIIT protocol.

Southern Brazilian native fruit shows neurochemical, metabolic and behavioral benefits in an animal model of metabolic syndrome.

In this work, we evaluated the effects of Psidium cattleianum (Red Type) (PcRT) fruit extract on metabolic, behavioral, and neurochemical parameters in rats fed with a highly palatable diet (HPD) consisted of sucrose (65% carbohydrates being 34% from condensed milk, 8% from sucrose and 23% from starch, 25% protein and 10% fat). Animals were divided into 4 groups: standard chow, standard chow + PcRT extract (200 mg/Kg/day by gavage), HPD, HPD + extract. The animals were treated for 150 days. Concerning chemical profiling, LC/PDA/MS/MS analysis revealed cyanidin-3-O-glucoside as the only anthocyanin in the PcRT extract. Our results showed that the animals exposed to HPD presented glucose intolerance, increased weight gain and visceral fat, as well as higher serum levels of glucose, triacylglycerol, total cholesterol, LDL-cholesterol and interleukin-6. These alterations were prevented by PcRT. In addition, HPD caused an increase in immobility time in a forced swimming test and the fruit extract prevented this alteration, indicating an antidepressant-like effect. PcRT treatment also prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD consumption. Moreover, PcRT extract was able to restore Ca2+-ATPase activity in the prefrontal cortex, hippocampus, and striatum, as well as Na+,K+-ATPase activity in the prefrontal cortex and hippocampus. PcRT treatment decreased thiobarbituric acid-reactive substances, nitrite, and reactive oxygen species levels and prevented the reduction of superoxide dismutase activity in all cerebral structures of the HPD group. Additionally, HPD decreased catalase in the hippocampus and striatum. However, the extract prevented this change in the hippocampus. Our results showed that this berry extract has antihyperglycemic and antihyperlipidemic effects, and neuroprotective properties, proving to be a potential therapeutic agent for individuals with metabolic syndrome.

Quercetin treatment regulates the Na+,K+-ATPase activity, peripheral cholinergic enzymes, and oxidative stress in a rat model of demyelination.

Quercetin is reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in the human diet has attracted the attention of the scientific community, resulting in a huge output of in vitro and in vivo (preclinical) studies. Therefore, we hypothesized that quercetin can protect Na+,K+-ATPase activity in the central nervous system, reestablish the peripheral cholinesterases activities, and reduce oxidative stress during demyelination events in rats. In line with this expectation, our study aims to find out how quercetin acts on the Na+,K+-ATPase activity in the central nervous system, peripheral cholinesterases, and stress oxidative markers in an experimental model of demyelinating disease. Wistar rats were divided into 4 groups: vehicle, quercetin, ethidium bromide (EB), and EB plus quercetin groups. The animals were treated once a day with vehicle (ethanol 20%) or quercetin 50 mg/kg for 7 (demyelination phase, by gavage) or 21 days (remyelination phase) after EB (0.1%, 10 µL) injection (intrapontine).The encephalon was removed, and the pons, hypothalamus, cerebral cortex, hippocampus, striatum, and cerebellum were dissected to verify the Na+,K+-ATPase activity. Our results showed that quercetin protected against reduction in Na+,K+-ATPase in the pons and cerebellum in the demyelination phase, and it increased the activity of this enzyme in the remyelination phase. During the demyelination, quercetin promoted the increase in acetylcholinesterase activity in whole blood and lymphocytes induced by EB, and it reduced the increase in acetylcholinesterase activity in lymphocytes in the remyelination phase. On day 7, EB increased the superoxide dismutase and decreased catalase activities, as well as increased the thiobarbituric acid-reactive substance levels. Taken together, these results indicated that quercetin regulates the Na+,K+-ATPase activity, affects the alterations of redox state, and participates in the reestablishment of peripheral cholinergic activity during demyelinating and remyelination events.