Oxidative Stress In Hippocampus Research Articles

Predictable chronic mild stress promotes recovery from LPS-induced depression

Clinical depression is frequently comorbid with chronic inflammatory disease, and neuroinflammation is currently proposed as a key mechanism in major depressive disorders. Different from unpredictable chronic stress, which is a well-established animal model for depression, predictable chronic mild stress (PCMS), a routine stress experienced in day-to-day life, has been demonstrated to improve mood and memory. In the present study, we assess the effects of PCMS (5 min of daily restrain stress for 4 weeks) on depressive-like behavior, neuroinflammation, oxidative stress, and pyrin domain containing three (NLRP3) activation in hippocampus of mice subjected to peripheral immune challenge by lipopolysaccharide (LPS). We found that PCMS facilitated the recovery from LPS-induced depressive- or anxiety-like behavior. Concurrent with the reversal of abnormal behavioral changes, PCMS suppressed LPS-induced proinflammatory cytokine expression, microglia activation, and oxidative stress in hippocampus. Correspondingly, PCMS inhibited LPS-induced overactivation of NLRP3 inflammasome components (NLRP3, ASC, and Caspase-1), and interleukin 1 beta (IL-1β) maturation. Nrf2 (nuclear factor (erythroid-derived 2)-like 2) signaling was demonstrated to inhibit NLRP3 inflammasome overactivation and oxidative stress. PCMS activated Nrf2 signaling and inhibited thioredoxin (Trx)-interacting protein (TXNIP) expression in LPS-treated mice. Collectively, present data suggest that PCMS, contrary to severe and uncontrolled stress, alleviated impairments of the Nrf2-TXNIP-Trx system and may contribute to inflammatory brain damage and the imbalance of cellular redox homeostasis in depressed mice. This study provides a mechanistic link to the resilience of PCMS to LPS-induced behavioral deficits.

Cerebrolysin attenuates ethanol-induced spatial memory impairments through inhibition of hippocampal oxidative stress and apoptotic cell death in rats.

The present study investigates the potential neuroprotective effect of cerebrolysin (CBL), a combination of neurotrophic factors, on the cognitive and biochemical alterations induced by chronic ethanol administration in rats. The animals were divided into five groups as follows: control; ethanol (4g/kg, for 30 days) plus normal saline (Ethanol+NS); ethanol plus CBL 1mL/kg (Ethanol+CBL 1), ethanol plus CBL 2.5mL/kg (Ethanol+CBL 2.5); and ethanol plus CBL 5mL/kg (Ethanol+CBL 5). The Morris water maze (MWM) test was performed to assess cognitive impairment. The status of the lipid peroxidation marker MDA, antioxidant capacity, as well as alterations of the apoptotic factors such as Bcl-2, BAX, and cleaved caspase-9 and -3, were evaluated in the hippocampus. The results showed that CBL treatment not only normalized the increased MDA levels in the alcoholic rats and enhanced antioxidant defense, but also reduced the Bax/Bcl-2 ratio and cleaved caspase-9 and -3 in the hippocampus. These results were parallel with improvement in spatial memory performance in the MWM test. The findings of the present study provide evidence for the promising therapeutic effect of CBL in chronic ethanol consumption through counteracting oxidative stress and apoptosis markers.

Protective Effect of Dorema glabrum on Induced Oxidative Stress by Diazinon in Hippocampus of Rat

Introduction: Diazinon (DZN) administration produces lipid peroxidation as an indicator of oxidative stress in the brain. Some medicinal plants such as Dorema glabrum has antioxidant properties, so can be used as an antioxidant that may protect neurons from oxidative stress. The aim of present study was to investigate the effect of D. glabrum against DZN-induced oxidative stress in hippocampus.
 Methods: Twenty-four adult male Wistar rats were used in this study. The rats randomly were divided into four groups including a control group, and two groups received different doses of D. glabrum (40 and 80 mg/kg) as pre-treatment for 21 days with DZN (100 mg/Kg) that was injected intraperitoneally (ip) in last day of D. glabrum usage, and one group received only DZN. Thiobarbituric acid reactive substances (TBARS), which are the indicators of lipid peroxidation, and the activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase and catalase) were determined in the ratsʼ hippocampus.
 Results: Administration of DZN significantly increased TBARS levels and superoxide dismutase activity and decreased glutathione peroxidase activity but there were no significant changes in catalase activity in the hippocampus. Combined D. glabrum and DZN treatment, caused a significant increase in glutathione peroxidase, a significant decrease of TBARS and a significant decrease in superoxide dismutase and again no significant changes in catalase activity in the rats’ hippocampus when compared to the rats treated with DZN.
 Conclusion: Our study demonstrated that D. glabrum had an amelioratory effect on oxidative stress induced by DZN.

Exploring the potential of Desmodium gangeticum (L.) DC. extract against spatial memory deficit in rats

Background: A few published reports demonstrated the neuroprotective effect of Desmodium gangeticum (L.) DC. in an acute model of dementia. Objective: The purpose of the present study was to evaluate the preclinical efficacy of D. gangeticum against chronic dementia when administered prophylactically. Materials and Methods: Chronic spatial memory deficit was induced in rats by aluminum chloride (AlCl3, 10 mg/kg, i.p.). Treatment with hydroalcoholic whole plant extract of D. gangeticum (DG extract) was initiated 2 week before AlCl3 challenge and continued till the 51st day after the challenge, orally at the dose of 400 mg/kg/day. The spatial memory was assessed by Morris water maze test. Hippocampal and frontal cortex acetyl cholinesterase (AChE) and oxidative stress were assessed in diseased rat brains. Results: Chronic administration of AlCl3 produced spatial memory deficit in rats. Memory impairment was manifested in rats as an increase in escape latency and D-quadrant latency whereas a decrease in total time spent in D-quadrant. These behavioral alterations were reversed significantly by the treatment with DG extract. In addition, DG extract significantly increased the island time, indicating memory improvement. DG extract corrected the declined AChE in frontal cortex and altered frontal cortex/hippocampus catalase activity. Phytochemical investigation of the DG extract revealed large content of saponins among the other phytochemicals such as tannins, alkaloids, and flavonoids. Conclusion: These results indicate the possible prophylactic potential of saponin-rich DG extract against chronic memory deficit in rats.

Protective Effects of Centella asiatica on Cognitive Deficits Induced by D-gal/AlCl₃ via Inhibition of Oxidative Stress and Attenuation of Acetylcholinesterase Level.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cholinergic dysfunctions and impaired redox homeostasis. The plant Centella asiatica (CA) is renowned for its nutritional benefits and herbal formulas for promoting health, enhancing cognition, and its neuroprotective effects. The present study aims to investigate the protective role of CA on D-gal/AlCl3-induced cognitive deficits in rats. The rats were divided into six groups and administered with donepezil 1 mg/kg/day, CA (200, 400, and 800 mg/kg/day) and D-gal 60 mg/kg/day + AlCl3 200 mg/kg/day for 10 weeks. The ethology of the rats was evaluated by the Morris water maze test. The levels of acetylcholinesterase (AChE), phosphorylated tau (P-tau), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), in the hippocampus and cerebral cortex were estimated by enzyme-linked immunosorbent assay (ELISA). Additionally, the ultrastructure of the prefrontal cortex of the rats’ was observed using transmission electron microscopy (TEM). Rats administered with D-gal/AlCl3 exhibited cognitive deficits, decreased activities of SOD, and marked increase in AChE and MDA levels. Further, prominent alterations in the ultrastructure of the prefrontal cortex were observed. Conversely, co-administration of CA with D-gal/AlCl3 improved cognitive impairment, decreased AChE levels, attenuated the oxidative stress in hippocampus and cerebral cortex, and prevented ultrastructural alteration of neurons in the prefrontal cortex. Irrespective of the dose of CA administered, the protective effects were comparable to donepezil. In conclusion, this study suggests that CA attenuated the cognitive deficits in rats by restoring cholinergic function, attenuating oxidative stress, and preventing the morphological aberrations.

The effect of cilostazol on hippocampal memory and oxidative stress biomarkers in rat model of diabetes mellitus

Diabetes is a global public health crisis worldwide, particularly in developing countries. Diabetes is characterized by a consistent elevation in blood glucose level which leads to several complications including cognitive impairment. Hippocampus, a brain structure responsible for memory, is vulnerable to damage caused by hyperglycemia-induced oxidative stress. In this study, we evaluated the effect of cilostazol, a selective phosphodiesterase 3 inhibitor, on hippocampal memory and oxidative stress biomarkers in streptozotocin-induced diabetes model. Cilostazol was administered to rats intraperitoneally at dose 3 mg/kg. Spatial learning and memory were tested using radial arm water maze (RAWM). BDNF protein, TBARS levels and different antioxidant biomarkers were assessed after dissection of the hippocampus. The diabetic rats showed an increase in the number of the errors during RAWM performance. However, treatment with cilostazol could not showed an improvement in animal’s learning and memory performance. The results revealed that diabetic rats showed an increase in TBARS levels and a decrease in an antioxidant enzyme activities (superoxide dismutase (SOD) and glutathione peroxidase (GPx)). Moreover, cilostazol was able to normalize diabetes-induced reduction in the hippocampus activity of SOD and GPx. Moreover, administration of cilostazol normalized diabetes-induced increase in TBARS level, without any significant effect on BDNF level or catalase activity. In conclusion, cilostazol showed no improvement in the learning and memory functions which could be due to the lack of significant cognitive impairment induced by streptozotocin administration. However, cilostazol had shown antioxidant activity through normalization of hippocampal oxidative stress biomarkers.

Physical and cognitive training are able to prevent recognition memory deficits related to amyloid beta neurotoxicity

Alzheimer's disease (AD) is characterized by the presence of amyloid-β (Aβ), oxidative damage and neuronal degeneration, which, together with other pathological events, promote progressive memory loss and cognitive decline. Non-pharmacological strategies have been study to provide some protection against the development of AD. Considering that physical exercise neuroprotective effects on prevention of cognitive deficits are well elucidate, it is important clarify the effects of cognitive training, and verify if they are similar or comparable to those observed for physical exercise. Here we divided male adult Wistar rats in six groups: control, which rats were not submitted to any intervention; Aβ, which rats were submitted to hippocampal infusion of Aβ; physical exercise (PE), which rats were submitted to 4 weeks of PE training; PE + Aβ, which rats were submitted to 4 weeks of PE training followed by hippocampal infusion of Aβ; cognitive exercise (CE), which rats were submitted to 4 weeks of CE training; and, CE + Aβ, which rats were submitted to 4 weeks of CE training followed by hippocampal infusion of Aβ. Ten days after Aβ infusion, short (STM) and long-term (LTM) object recognition memory, as well as hippocampal oxidative stress (ROS levels by DCFH test), lipid peroxidation (TBARS), total antioxidant capacity (FRAP) and hippocampal histology were evaluated. Both PE and CE were effective in protect cognitive function against memory deficits related to Aβ neurotoxicity, preventing oxidative stress and damage and hippocampal cellular disorganization. So, cognitive training seems to be as good as physical training in the prevention of memory deficits related to Aβ and seems to share some mechanisms of actions, as oxidative stress prevention.

Glucagon-Like Peptide-1 Cleavage Product Improves Cognitive Function in a Mouse Model of Down Syndrome.

Currently there is no effective therapy available for cognitive impairments in Down syndrome (DS), one of the most prevalent forms of intellectual disability in humans associated with the chromosomes 21 trisomy. Glucagon-like peptide-1 (GLP-1) is an incretin hormone that maintains glucose homeostasis by stimulating insulin secretion. Its natural cleavage product GLP-1 (9-36) lacks insulinotropic effects and has a low binding affinity for GLP-1 receptors; thus, GLP-1 (9-36) has historically been identified as an inactive metabolite. Conversely, recent work has demonstrated interesting physiological properties of GLP-1 (9-36) such as cardioprotection and neuroprotection. We have previously shown that GLP-1 (9-36) administration enhances neuronal plasticity in young WT mice and ameliorates cognitive deficits in a mouse model of Alzheimer’s disease. Here, we report that systemic administration of GLP-1 (9-36) in Ts65Dn DS model mice of either sex resulted in decreased mitochondrial oxidative stress in hippocampus and improved dendritic spine morphology, increase of mature spines and reduction of immature spines. Importantly, these molecular alterations translated into functional changes in that long-term potentiation failure and cognitive impairments in TsDn65 DS model mice were rescued with GLP-1 (9-36) treatment. We also show that chronic GLP-1 (9-36) treatment did not alter glucose tolerance in either WT or DS model mice. Our findings suggest that GLP-1 (9-36) treatment may have therapeutic potential for DS and other neurodegenerative diseases associated with increased neuronal oxidative stress.

17-β estradiol Attenuated Hippocampus Oxidative Stress in an Ethidium Bromide-Induced Multiple Sclerosis Model among Adult Male Rats

17-β estradiol Attenuated Hippocampus Oxidative Stress in an Ethidium Bromide-Induced Multiple Sclerosis Model among Adult Male Rats

Egg White Hydrolysate as a functional food ingredient to prevent cognitive dysfunction in rats following long-term exposure to aluminum

Aluminum (Al), which is omnipresent in human life, is a potent neurotoxin. Here, we have tested the potential for Egg White Hydrolysate (EWH) to protect against changes in cognitive function in rats exposed to both high and low levels of Al. Indeed, EWH has been previously shown to improve the negative effects induced by chronic exposure to heavy metals. Male Wistar rats received orally: Group 1) Low aluminum level (AlCl3 at a dose of 8.3 mg/kg b.w. during 60 days) with or without EWH treatment (1 g/kg/day); Group 2) High aluminum level (AlCl3 at a dose of 100 mg/kg b.w. during 42 days) with or without EWH treatment (1 g/kg/day). After 60 or 42 days of exposure, rats exposed to Al and EWH did not show memory or cognitive dysfunction as was observed in Al-treated animals. Indeed, co-treatment with EWH prevented catalepsy, hippocampal oxidative stress, cholinergic dysfunction and increased number of activated microglia and COX-2-positive cells induced by Al exposure. Altogether, since hippocampal inflammation and oxidative damage were partially prevented by EWH, our results suggest that it could be used as a protective agent against the detrimental effects of long term exposure to Al.

Neuromodulatory potential of phenylpropanoids; para-methoxycinnamic acid and ethyl-p-methoxycinnamate on aluminum-induced memory deficit in rats

Para-methoxycinnamic acid (PMCA) and Ethyl-p-methoxycinnamate (EPMC) are reported to possess neuroprotective effect in reversing an acute memory deficit. However, there is a dearth of evidence for their therapeutic effect in chronic memory deficit. Thus, there is a scope to study these derivatives against the chronic model of cognitive dysfunction. The present study was aimed to determine the cognitive enhancing activity of PMCA and EPMC in aluminum-induced chronic dementia. Cognitive enhancing property of PMCA and EPMC was assessed using Morris water maze by analyzing spatial memory parameters such as escape latency, D-quadrant latency, and island entries. To find a possible mechanism, the effect of test compounds on altered acetylcholinesterase (AChE) activity and oxidative stress was determined in the hippocampus and frontal cortex of rats. Docking interaction of these derivatives with acetylcholinesterase enzyme and glutamate receptors was also studied. Treatment with PMCA and EPMC showed a significant improvement in spatial memory markers and altered hippocampal AChE activity in rats with cognitive dysfunction. The implication of hippocampal and cortical oxidative stress in memory impairment was confirmed with decreased catalase/increased thiobarbituric acid reactive substances (TBARS) in rats. PMCA and EPMC reversed the oxidative stress in the brain by negatively affecting TBARS levels. Against depleted catalase levels, PMCA was more effective than EPMC in raising the depleted catalase levels. In silico analysis revealed poor affinity of EPMC and PMCA with AChE enzyme and glutamate receptor. To conclude, PMCA and EPMC exerted cognitive enhancing property independent of direct AChE and glutamate receptor inhibition.

Effect of berberine chloride on caspase-3 dependent apoptosis and antioxidant capacity in the hippocampus of the chronic cerebral hypoperfusion rat model.

Objective(s):The main goal of the current research was to examine the effects of Berberine (BBR) on apoptotic signaling and hippocampal oxidative stress induced by common carotid artery occlusion.Materials and Methods:Chronic cerebral hypoperfusion (CCH) model was created by occluding the two common carotid arteries (two-vessel occlusion [2VO]) permanently. BBR (50 and 100 mg/kg/daily) was intra-gastrically administered to ischemic rats. Neuronal survival was evaluated by Nissl staining. The levels of malondialdehyde (MDA) and antioxidant enzymes, including catalase (CAT) and superoxide dismutase (SOD), along with the activities of caspase 3 were estimated in the hippocampus 2 month after treating the rats with 2VO.Results:According to findings of the present research, the BBR therapy inhibited the neuro-degeneration of hippocampus. BBR also significantly decreased the amount of MDA and activity of caspase 3 in the hippocampus. Furthermore, the administration of BBR alleviated the lowered activities of SOD and CAT after 2VO surgery.Conclusion:The antioxidant and antiapoptotic properties of BBR might play important roles in improving functional outcomes and might have significant neuroprotective effects on the CCH damage.

HYDROALCOHOLIC EXTRACT OF SWERTIA CHIRATA AND SWERTIA CORDATA ATTENUATES HYPOXIA-MEDIATED MEMORY DYSFUNCTION BY IMPROVING NEURONAL SURVIVAL IN WISTAR RATS

Objective: Swertia chirata and Swertia cordata have been used in traditional and folk medicines to treat several mental disorders. However, the mechanistic and experimental justification to its traditional use is lacking. The present study was aimed to investigate the neuromodulatory potential of S. chirata and S. cordata during hypoxia-induced neuronal damage in Wistar rats and to determine the underlying mechanism.
 Methods: Animals were divided into six groups (n=5). Hypoxia was inflicted by subjecting animals to the atmosphere having 10% O2 for 3 days. Animals were administered 100 mg/kg hydroalcoholic extract of S. chirata and S. cordata orally once daily for 7 days, after which motor coordination (Rotarod test) and memory functions (active avoidance test and passive avoidance test) were evaluated. Animals were sacrificed and biochemical investigations for oxidative stress and histopathology were performed.
 Results: Subjecting animals to hypoxia resulted in marked memory dysfunction, and extract treatments improved memory functions in active avoidance and passive avoidance task. Hypoxiainduced the marked oxidative stress as indicated by the significantly elevated reactive oxygen species and lipid peroxidation and depleted catalase and glutathione levels in the hippocampus. S. chirata and S. cordata treatment alleviated oxidative stress in the hippocampus region of the brain. Brain histopathology confirmed that hypoxia resulted in significant neuronal damage and extract treatment efficiently rescued neurons from hypoxic damage. Overall, S. chirata extract treatment was observed to have better neuromodulatory effect than S. cordata during hypoxia.
 Conclusion: Hypoxia induced memory dysfunction by inflicting neuronal damage and oxidative stress in the hippocampus region of the brain. The hydroalcoholic extract of S. chirata and S. cordata improved memory functions in hypoxic animals by alleviating hippocampal oxidative stress and by improving neuronal morphology and survival.

Protective effects of 5-HT1A receptor antagonist and 5-HT2A receptor agonist on the biochemical and histological features in a rat model of Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disorder and neuropathologically characterized by the aggregation of amyloid-beta (Aβ) plaques, neurofibrillary tangles, enhanced oxidative stress and neurodegeneration. Involvement of serotonergic systems in AD has been supposed and it is suggested that serotonin receptors modulation may provide a novel therapeutic target for AD.This study aimed at investigating the protective effect of NAD-299 (the selective 5-HT1A receptor antagonist) and TCB-2 (the potent5-HT2A receptor agonist) on the hippocampal oxidative stress biomarkers and the number of intact neurons in streptozotocin (STZ)-induced Alzheimer's disease in rats.Fifty adult male Wistar rats weighing 250–300 g were divided into five groups: sham, STZ-treated, STZ + NAD-299 (5 μg/1 μl icv), STZ + TCB-2 (5 μg/1 μl icv) and STZ + NAD-299 (5 μg/0.5 μl icv) +TCB-2 (5 μg/0.5 μl icv). At the end of the study, the rats were weighed, then hippocampal oxidative stress markers [total antioxidant capacity (TAC), malondialdehyde (MDA), the total thiol group (TTG), and DNA damage] were measured. In addition, the number of intact neurons in the CA1 area of the hippocampus was determined using hematoxylin and eosin staining.The results showed that icv injection of STZ reduced hippocampal TAC, TTG levels and intact pyramidal cells and increased DNA damage and MDA levels in the hippocampus of STZ-treated rats. Icv administration of NAD-299, TCB-2, and NAD-299+TCB-2 increased TAC and TTG contents and hippocampal intact neurons and reduced hippocampal DNA damage, MDA levels in icv-STZ treated rats. Moreover, there was no significant difference in weight changes among the experimental groups.According to the obtained results, it is suggested that 5-HT1A receptor antagonist (NAD-299) and 5-HT2A receptor agonist (TCB-2) can reduce oxidative stress and neuronal loss in a rat model of AD and may prevent the AD progression.

The Sex-specific Effects of LPS on Depressive-like Behavior and Oxidative Stress in the Hippocampus of the Mouse

Many human and animal studies have implicated inflammation as a mediator of oxidative stress and a possible contributor to hippocampal atrophy in the pathophysiology of major depressive disorder. We aimed to examine the effect of peripheral, systemic inflammation on oxidative stress and apoptosis in the hippocampi of male and female mice. We hypothesized that (1) lipopolysaccharide (LPS) would induce depressive-like behavior and hippocampal oxidative stress after 1 day in males, and (2) that a single LPS exposure would result in hippocampal apoptosis at 28 days. Further, we predicted that female sex would confer protection from the molecular and behavioral deleterious effects of LPS. Males exhibited depressive-like behavior 24 h after LPS administration compared to the males given saline. Female mice did not exhibit depressive-like behavior after LPS compared to females in the saline group. Males given LPS also had increased levels of superoxide dismutase (SOD) I in the hippocampus by 24 h compared to the saline group. At 28 days, we found decreased levels of brain derived neurotrophic factor (BDNF) protein in males given LPS compared to males given saline. Moreover, males given LPS showed increased apoptosis. Our work will provide insight into the underlying biology in males and females with MDD, and potentially underlying differences between the sexes. Also, our work will hopefully inform optimal clinical treatments that may indeed differ between the sexes.

A multifunctional compound ebselen reverses memory impairment, apoptosis and oxidative stress in a mouse model of sporadic Alzheimer's disease

Alzheimer 's disease (AD) is characterized by progressive cognitive decline including memory impairment, cortical dysfunction, and neuropsychiatric disturbances. The drug discovery to treat AD consists to develop compounds able to act in multiple molecular targets involved in the pathogenesis of the disease and the repositioning of old drugs for new application. This way, the intracerebroventricular (icv) injection of streptozotocin (STZ) has been used as a metabolic model of sporadic AD. The aim of the present study was to investigate whether ebselen (1–10 mg/kg), a multifunctional selenoorganic compound, ameliorates memory impairment, hippocampal oxidative stress, apoptosis and cell proliferation in a mouse model of sporadic AD induced by icv STZ (3 mg/kg, 1 μl/min). The administration of ebselen (10 mg/kg, i.p.) reversed memory impairment and hippocampal oxidative stress, by increasing the activities of antioxidant enzymes and the level of a non-enzymatic antioxidant defense, in Swiss mice administered with icv STZ. The anti-apoptotic property of ebselen was demonstrated by its effectiveness against the increase in the ratios of Bax/Bcl-2, cleaved PARP/PARP and the cleaved caspase-3 levels in the hippocampus of icv STZ mice. Although ebselen reversed memory impairment, it was ineffective against the reduction in the number of BrdU positive cells induced by icv STZ. In conclusion, the multifunctional selenoorganic compound ebselen was effective to reverse memory impairment, hippocampal oxidative stress and apoptosis in a mouse model of sporadic AD induced by icv STZ.

259 - LPS-induced systemic neonatal inflammation: blockage of P2X7R by BBG on neonatal phase decreases oxidative stress in hippocampus of adult rats

The neonatal period is marked by intense maturation of the immune and central nervous systems and the exposure to inflammation during this phase of life may produce long-term effects on the neural system. Here, we examined the impact of neonatal lipopolysaccharide (LPS) exposure on anxiety and pain sensitivity, as well as the superoxide production in adult rats. We also assessed if the blockage of the P2X7R by its antagonist BBG could modulate the effects of LPS on the central nervous system. Wistar male rats were injected with saline (0.9% solution), LPS (1mg/kg, Escherichia coli) or LPS and BBG (50mg/Kg) on postnatal days (PNDs) 1, 3, 5 and 7. Anxiety was evaluated in the Elevated Plus Maze test and nociception in the Hot Plate and Tail Flick tests during adulthood at PNDs 80, 82 and 84 respectively. At PND89, euthanasia was performed and the brain collected for measuring superoxide levels by Dihydroethidium (DHE). No statistical differences were found in Elevated plus maze, Hot-plate nor Tail-flick tests. However, the persistent systemic neonatal inflammation lead to a higher production of superoxide anion in the hippocampus and the blockage of the P2X7R decreased its production (p

Reviewing the effects of dietary salt on cognition: mechanisms and future directions.

Consumption of salt exceeds dietary guidelines for many countries around the world, despite efforts to increase awareness of the potential cardiovascular health risks. Emerging evidence, primarily from rodent models, indicates that high salt intake may also impair aspects of cognitive function. To our knowledge, here we provide the first review of the effects of salt on cognition. To review literature on the effects of high-salt diets on cognitive measures across human and non-human animal research to generate targeted questions for future studies. Non-systematic literature review of studies manipulating (in rodents) or measuring (in humans) salt intake and assessing performance on cognitive measures. Studies in humans have focused on older populations and show mixed associations between salt intake and cognitive performance. By contrast, most rodent studies have found impairments in cognition following chronic consumption of high-salt (typically 7-8%) diets. Most report impairments in tasks assessing spatial memory with corresponding increases in hippocampal oxidative stress and inflammatory responses originating in the gut. Notably, several rodent studies reported that high-salt diets impaired cognitive function in the absence of blood pressure changes. Contrasting results from human and animal studies emphasise the need for further studies to clarify whether salt intake affects cognition. Testing cognition in high-salt diet models that induce hypertension will increase the translatability of future studies in rodents. A challenge for research in humans is isolating the effects of salt from those of fat and sugar that tend to co-occur in 'western' diets.

Chronic administration of quetiapine attenuates the phencyclidine-induced recognition memory impairment and hippocampal oxidative stress in rats.

The underlying mechanism of atypical antipsychotics in treating cognitive impairment in schizophrenia is unclear. The aim of the present study was to evaluate the effects of quetiapine, an atypical antipsychotic drug, on object recognition memory and hippocampal oxidative stress in a phencyclidine (PCP) rat model of schizophrenia. Rats were treated with chronic quetiapine (10 mg/kg/day, intraperitoneally) for 16 days or acute quetiapine (10 mg/kg/day, intraperitoneally) on day 16. On day 16, 1 h after the administration of quetiapine, the rats were administered PCP (50 mg/kg, subcutaneously). After the last object recognition behavioral test on day 18, the rats were killed for the measurement of hippocampal protein expression of nitrotyrosine, a protein marker of oxidative stress. The results showed that chronic quetiapine significantly attenuated object recognition memory impairment and hippocampal oxidative stress in the PCP-injected rats. These suggest that the attenuating effect of chronic quetiapine on hippocampal oxidative stress may be related to quetiapine's beneficial effects on object recognition memory in PCP rats, and further suggest that neuroprotective mechanisms are involved in chronic quetiapine treatment.

Effects of cafeteria diet on memory and hippocampal oxidative stress in a rat model of Alzheimer-like disease: Neuroprotection of green tea supplementation

Here we investigate the neuroprotective role of green tea (GT) when cafeteria diet (CAF) is associated with a model of β-Amyloid (Aβ) injection that induces cognitive impairments related to Alzheimer disease (AD). Wistar male rats were supplemented with GT, CAF, or GT plus CAF for 8 weeks before intra-hippocampal injection of Aβ peptide (2 μL of Aβ-25–35, CA1 region). AD-like and sham rats were submitted to memory tests. Oxidative status was quantified in the bilateral hippocampus, and plasmatic triglycerides, total cholesterol, glucose, and AChE activity were determined. CAF per se does not impair object and social recognition memories. Neuroprotective role of GT was confirmed also in the conditions of CAF combined with AD-like. GT supplementation and CAF, either isolated or combined, avoid oxidative stress and damage in the hippocampus. We conclude that CAF did not influence oxidative damage and memory deficits resultant of β-Amyloid injection when GT is simultaneously ingested.