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.

Curcumin attenuates memory deficits and the impairment of cholinergic and purinergic signaling in rats chronically exposed to cadmium.

This study investigated the protective effect of curcumin on memory loss and on the alteration of acetylcholinesterase and ectonucleotidases activities in rats exposed chronically to cadmium (Cd). Rats received Cd (1 mg/kg) and curcumin (30, 60, or 90 mg/kg) by oral gavage 5 days a week for 3 months. The animals were divided into eight groups: vehicle (saline/oil), saline/curcumin 30 mg/kg, saline/curcumin 60 mg/kg, saline/curcumin 90 mg/kg, Cd/oil, Cd/curcumin 30 mg/kg, Cd/curcumin 60 mg/kg, and Cd/curcumin 90 mg/kg. Curcumin prevented the decrease in the step-down latency induced by Cd. In cerebral cortex synaptosomes, Cd-exposed rats showed an increase in acetylcholinesterase and NTPDase (ATP and ADP as substrates) activities and a decrease in the 5'-nucleotidase activity. Curcumin was not able to prevent the effect of Cd on acetylcholinesterase activity, but it prevented the effects caused by Cd on NTPDase (ATP and ADP as substrate) and 5'-nucleotidase activities. Increased acetylcholinesterase activity was observed in different brain structures, whole blood and lymphocytes of the Cd-treated group. In addition, Cd increased lipid peroxidation in different brain structures. Higher doses of curcumin were more effective in preventing these effects. These findings show that curcumin prevented the Cd-mediated memory impairment, demonstrating that this compound has a neuroprotective role and is capable of modulating acetylcholinesterase, NTPDase, and 5'-nucleotidase activities. Finally, it highlights the possibility of using curcumin as an adjuvant against toxicological conditions involving Cd exposure. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 70-83, 2017.

Piracetam prevents scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities.

Piracetam improves cognitive function in animals and in human beings, but its mechanism of action is still not completely known. In the present study, we investigated whether enzymes involved in extracellular adenine nucleotide metabolism, adenosine triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase and adenosine deaminase (ADA) are affected by piracetam in the hippocampus and cerebral cortex of animals subjected to scopolamine-induced memory impairment. Piracetam (0.02 µmol/5 µL, intracerebroventricular, 60 min pre-training) prevented memory impairment induced by scopolamine (1 mg/kg, intraperitoneal, immediately post-training) in the inhibitory avoidance learning and in the object recognition task. Scopolamine reduced the activity of NTPDase in hippocampus (53 % for ATP and 53 % for ADP hydrolysis) and cerebral cortex (28 % for ATP hydrolysis). Scopolamine also decreased the activity of 5'-nucleotidase (43 %) and ADA (91 %) in hippocampus. The same effect was observed in the cerebral cortex for 5'-nucleotidase (38 %) and ADA (68 %) activities. Piracetam fully prevented scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities in synaptosomes from cerebral cortex and hippocampus. In vitro experiments show that piracetam and scopolamine did not alter enzymatic activity in cerebral cortex synaptosomes. Moreover, piracetam prevented scopolamine-induced increase of TBARS levels in hippocampus and cerebral cortex. These results suggest that piracetam-induced improvement of memory is associated with protection against oxidative stress and maintenance of NTPDase, 5'-nucleotidase and ADA activities, and suggest the purinergic system as a putative target of piracetam.

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.

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.

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.

In vitro and in vivo interactions of aluminum on NTPDase and AChE activities in lymphocytes of rats.

Al adjuvants are used in vaccines to increase the immune response. NTPDase and AChE play a pivotal role and act in the regulation of the immune system. The effect of Al exposure in vitro and in vivo on NTPDase and AChE activities in the lymphocytes of rats was determined. In vitro, ATP hydrolysis was decreased by 20.4% and 17.3% and ADP hydrolysis was decreased by 36.5% and 34.8%, in groups D and E, respectively, when compared to the control. AChE activity was increased by 157.3%, 152.5%, 74.7% and 90.8% in groups B, C, D, and E, respectively, when compared to the control. In vivo, ATP hydrolysis was increased by 85% and 86% and ADP hydrolysis was increased by 104.2% and 74%, in Al plus citrate and Al groups, respectively, when compared to the control. AChE activity was increased by 50.7% in Al plus citrate and by 28.6% in Al groups, when compared to the control. Our results show that Al exposure both in vitro and in vivo altered NTPDase and AChE activities in lymphocytes. These results may demonstrate the ability of Al to elicit the immune system, where NTPDase and AChE activities can act as purinergic and cholinergic markers in lymphocytes.

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.

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.

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.

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.

A comparative study of the effect of the dose and exposure duration of anabolic androgenic steroids on behavior, cholinergic regulation, and oxidative stress in rats.

The aim of this study was to assess if the dose and exposure duration of the anabolic androgenic steroids (AAS) boldenone (BOL) and stanazolol (ST) affected memory, anxiety, and social interaction, as well as acetylcholinesterase (AChE) activity and oxidative stress in the cerebral cortex (CC) and hippocampus (HC). Male Wistar rats (90 animals) were randomly assigned to three treatment protocols: (I) 5 mg/kg BOL or ST, once a week for 4 weeks; (II) 2.5 mg/kg BOL or ST, once a week for 8 weeks; and (III) 1.25 mg/kg BOL or ST, once a week for 12 weeks. Each treatment protocol included a control group that received an olive oil injection (vehicle control) and AAS were administered intramuscularly (a total volume of 0.2 ml) once a week in all three treatment protocols. In the BOL and ST groups, a higher anxiety level was observed only for Protocol I. BOL and ST significantly affected social interaction in all protocols. Memory deficits and increased AChE activity in the CC and HC were found in the BOL groups treated according to Protocol III only. In addition, BOL and ST significantly increased oxidative stress in both the CC and HC in the groups treated according to Protocol I and III. In conclusion, our findings show that the impact of BOL and ST on memory, anxiety, and social interaction depends on the dose and exposure duration of these AAS.

Caffeine prevents high-intensity exercise-induced increase in enzymatic antioxidant and Na+-K+-ATPase activities and reduction of anxiolytic like-behaviour in rats.

OBJECTIVE: Here we investigated the impact of chronic high-intensity interval training (HIIT) and caffeine consumption on the activities of Na+-K+-ATPase and enzymes of the antioxidant system, as well as anxiolytic-like behaviour in the rat brain. METHODS: 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). Rats were trained three times per week for 6 weeks, and caffeine was administered 30 minutes before training. We assessed the anxiolytic-like behaviour, Na+-K+-ATPase, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, levels of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) in the brain. RESULTS AND DISCUSSION: HIIT-induced anxiolytic-like behaviour increased Na+-K+-ATPase and GPx activities and TBARS levels, altered the activities of SOD and CAT in different brain regions, and decreased GSH levels. Caffeine, however, elicited anxiogenic-like behaviour and blocked HIIT effects. The combination of caffeine and HIIT prevented the increase in SOD activity in the cerebral cortex and GPx activity in three brain regions. Our results show that caffeine promoted anxiogenic behaviour and prevented HIIT-induced changes in the antioxidant system and Na+-K+-ATPase activities.

Impacts of dose and time of boldenone and stanazolol exposure in inflammatory markers, oxidative and nitrosative stress and histopathological changes in the rat testes.

The present study was conducted to analyze the adverse effects of the anabolic steroids boldenone (BOL) and stanazolol (ST) in the reproductive function of male rats. These molecules were administered using three different protocols. In Protocol I, BOL and ST were administered in a higher dose than what is recommended but for a short period. In Protocol II, a moderate dose of these compounds was applied for an intermediate period, whereas in Protocol III a reduced dose was administered but for an extended period. Notably, Protocol I and III resulted in increased levels of reactive oxygen specimens (ROS [I, p < 0.01] [III, p < 0.001)]) and nitrite plus nitrate (NOx [I, p < 0.01] [II, p < 0.01] [III,p < 0.05]), respectively, whereas non-protein thiols (NPSH) levels were decreased only after Protocol III (p < 0.01). Myeloperoxidase activity was significantly increased after treatment with BOL in protocol II (p < 0.01) and III (p < 0.05) than with ST in protocol III (p < 0.05). Boldenone and ST also caused a significant up-regulation in the levels of serum testosterone when protocols I (p < 0.01) and II (p < 0.05) were performed. There were also visible histopathological alterations in the testes induced by treatment with BOL, namely degenerative changes primarily characterized by a decrease in the germinal epithelium. Together, these results suggest that the administration of BOL or ST exerts a significantly harmful effect in the testes of male rats. Moreover, all the treatment protocols used in this study induced deleterious effects on the testes, as indicated by the different biochemical parameters investigated. However, only the protocols of longer exposure time (II and III) induced morphological changes compatible with infertility.

Evaluation of the biochemical, inflammatory and oxidative profile of obese patients given clinical treatment and bariatric surgery.

BACKGROUND: We investigated the biochemical and inflammatory parameters as well as biomarkers of oxidative stress in morbidly obese patients before and after bariatric surgery and clinical treatment. METHODS: This study was conducted using 60 individuals (10 men and 50 women) distributed into 3 groups: the control group, 20 non-diabetic obese patients given clinical treatment, the bariatric group, 20 non-diabetic obese patients given a Roux-en-Y bypass gastroplasty, and the bariatric diabetic group, 20 diabetic obese patients given a Roux-en-Y bypass gastroplasty. Measurements were made before and 1, 3, 6, and 12months after surgery and clinical treatment. RESULTS: We showed a significant decrease in body weight, body mass index (BMI) and waist circumference, accompanied by a decrease in the lipid profile and glucose and glycated hemoglobin concentrations in the groups that received bariatric surgery. The concentrations of lipid peroxidation, carbonyl protein and NPSH, as well as superoxide dismutase (SOD) and catalase (CAT) activity, significantly decreased in both groups after surgery. The concentrations of inteleukin-6, inteleukin-1, TNF-α and resistin were also significantly lower, while adiponectin concentrations significantly increased 12months after bariatric surgery. No significant alterations were observed in the biochemical, inflammatory or oxidative parameters of the control group. CONCLUSIONS: Our findings demonstrate a decrease in body mass and a subsequent improvement in biochemical, metabolic and anthropometric parameters in patients given bariatric surgery. This may contribute to the reduction of oxidative damage in these patients and consequently a reduction in the risk of the development and progression of multiple co-morbidities associated with obesity.

Caffeine prevents changes in muscle caused by high-intensity interval training.

The use of ergogenic substances such as caffeine has become a strategy to enhance sports performance. In the present study we evaluated the effects of high-intensity interval training (HIIT) associated with caffeine intake on acetylcholinesterase (AChE) and Ca2+ATPase activity and glycogen levels in the muscles of rats were evaluated. The animals were divided in groups: control, caffeine 4 or 8mg/kg, HIIT, HIIT plus caffeine 4 or caffeine 8mg/kg. Our results showed a decrease in glycogen levels in muscle in all trained groups after acute session exercise, while that an increase in glycogen levels was observed in all groups in relation to control in chronic exercise protocol. HIIT increases the thickness of the left ventricle and the Ca2+-ATPase activity and decrease the AChE activity in gastrocnemius muscle. Caffeine treatment prevents changes in enzymes activities as well as left ventricular hypertrophy adaptation induced by HIIT. Our findings suggest that caffeine modulates crucial pathways for muscle contraction in HIIT.

Guanosine Protects Against Traumatic Brain Injury-Induced Functional Impairments and Neuronal Loss by Modulating Excitotoxicity, Mitochondrial Dysfunction, and Inflammation.

Traumatic brain injury (TBI) is one of the most common types of brain injuries that cause death or persistent neurological disturbances in survivors. Most of the promising experimental drugs were not effective in clinical trials; therefore, the development of TBI drugs represents a huge unmet need. Guanosine, an endogenous neuroprotective nucleoside, has not been evaluated in TBI to the best of our knowledge. Therefore, the present study evaluated the effect of guanosine on TBI-induced neurological damage. Our findings showed that a single dose of guanosine (7.5 mg/kg, intraperitoneally (i.p.) injected 40 min after fluid percussion injury (FPI) in rats protected against locomotor and exploratory impairments 8 h after injury. The treatment also protected against neurochemical damage to the ipsilateral cortex, glutamate uptake, Na+/K+-ATPase, glutamine synthetase activity, and alterations in mitochondrial function. The inflammatory response and brain edema were also reduced by this nucleoside. In addition, guanosine protected against neuronal death and caspase 3 activation. Therefore, this study suggests that guanosine plays a neuroprotective role in TBI and can be exploited as a new pharmacological strategy.

Anthocyanins control neuroinflammation and consequent memory dysfunction in mice exposed to lipopolysaccharide.

Peripheral inflammatory stimuli may activate a brain neuroinflammatory processes with consequences in brain function. The present study investigated if anthocyanins (ANT) consumption was able to prevent the memory loss, the neuronal damage, and the neuroinflammatory processes triggered by the intraperitoneal lipopolysaccharide (LPS) administration. C57BL6 male mice were treated with ANT (30-100 mg/kg by gavage). With a single dose or during 10 days, before be challenged with LPS (250 µg/kg intraperitoneally single administration), a classical inductor of inflammation. The data obtained showed that ANT was able to confer protection against the memory impairment after 10 days of ANT treatment (100 mg/kg). This phytonutrient also prevented the hypothermia episode induced by LPS. Moreover, ANT prevented the increase in protein carbonyl, NOx, and MDA levels in the hippocampus and cerebral cortex (4 and 24 h) in animal challenged with LPS. ANT showed a protective effect on the increase in the pro-inflammatory cytokines content, especially Interleukin (IL)-1ß, tumoral necrosis factor-α and on the reduction of IL-10 induced by LPS. ANT 100 mg/kg prevented the infiltration of peripheral immune cells in the hippocampus at 24 h post-LPS administration. In parallel, LPS increased the activity of myeloperoxidase in cortex and hippocampus, and ANT prevented this effect, also reducing microglia (Iba-1) and astrocyte (GFAP) immunoreactivity. Thus, our data support that ANT are a promising therapeutic component against brain disorders associated with process of neuroinflammation. Graphical Abstract ᅟ.

Neuroprotective effects of quercetin on memory and anxiogenic-like behavior in diabetic rats: Role of ectonucleotidases and acetylcholinesterase activities.

The present study investigated the protective effect of quercetin (Querc) on memory, anxiety-like behavior and impairment of ectonucleotidases and acetylcholinesterase (AChE) activities in brain of streptozotocin-induced diabetic rats (STZ-diabetes). The type 1 diabetes mellitus was induced by an intraperitoneal injection of 70mg/kg of streptozotocin (STZ), diluted in 0.1M sodium-citrate buffer (pH 4.5). Querc was dissolved in 25% ethanol and administered by gavage at the doses of 5, 25 and 50mg/kg once a day during 40days. The animals were distributed in eight groups of ten animals as follows: vehicle, Querc 5mg/kg, Querc 25mg/kg, Querc 50mg/kg, diabetes, diabetes plus Querc 5mg/kg, diabetes plus Querc 25mg/kg and diabetes plus Querc 50mg/kg. Querc was able to prevent the impairment of memory and the anxiogenic-like behavior induced by STZ-diabetes. In addition, Querc prevents the decrease in the NTPDase and increase in the adenosine deaminase (ADA) activities in SN from cerebral cortex of STZ-diabetes. STZ-diabetes increased the AChE activity in SN from cerebral cortex and hippocampus. Querc 50mg/kg was more effective to prevent the increase in AChE activity in the brain of STZ-diabetes. Querc also prevented an increase in the malondialdehyde levels in all the brain structures. In conclusion, the present findings showed that Querc could prevent the impairment of the enzymes that regulate the purinergic and cholinergic extracellular signaling and improve the memory and anxiety-like behavior induced by STZ-diabetes.

Anthocyanins suppress the secretion of proinflammatory mediators and oxidative stress, and restore ion pump activities in demyelination.

The aim of this study was to investigate the protective effect of anthocyanins (ANT) on oxidative and inflammatory parameters, as well as ion pump activities, in the pons of rats experimentally demyelinated with ethidium bromide (EB). Rats were divided in six groups: control, ANT 30 mg/kg, ANT 100 mg/kg, EB (0.1%), EB plus ANT 30 mg/kg and EB plus ANT 100 mg/kg. The EB cistern pons injection occurred on the first day. On day 7, there was a peak in the demyelination. During the 7 days, the animals were treated once per day with vehicle or ANT. It was observed that demyelination reduced Na(+),K(+)-ATPase and Ca(2+)-ATPase activities and increased 4-hydroxynonenal, malondialdehyde, protein carbonyl and NO2plus NO3 levels. In addition, a depletion of glutathione reduced level/nonprotein thiol content and a decrease in superoxide dismutase activity were also seen. The dose of 100 mg/kg showed a better dose-response to the protective effects. The demyelination did not affect the neuronal viability but did increase the inflammatory infiltrate (myeloperoxidase activity) followed by an elevation in interleukin (IL)-1ß, IL-6, tumor necrosis factor-α and interferon-γ levels. ANT promoted a reduction in cellular infiltration and proinflammatory mediators. Furthermore, ANT restored the levels of IL-10. Luxol fast blue staining confirmed the loss of myelin in the EB group and the protective effect of ANT 100 mg/kg. In conclusion, this study was the first to show that ANT are able to restore ion pump activities and protect cellular components against the inflammatory and oxidative damages induced by demyelination.