Hippocampal Malondialdehyde Research Articles

Fasudil attenuates lipopolysaccharide-induced cognitive impairment in C57BL/6 mice through anti-oxidative and anti-inflammatory effects: Possible role of aquaporin-4

IntroductionProcesses that generate systemic inflammation are strongly associated with neurodegenerative diseases. This study aimed to explore the potential anti-oxidative and anti-inflammatory effects of fasudil and its role in modulating aquaporin-4 (AQP-4) to improve cognitive impairment in a systemic inflammation model induced by lipopolysaccharide (LPS). Methodfourty C57BL/6 mice were assigned to four groups, including sham, LPS, sham+fasudil, and LPS+fasudil). Intraperitoneal LPS was given (500 μg/kg/day) at hours 0, 24, 48, and 72, and fasudil (30 mg/kg) administered intraperitoneal injections 2 hours after LPS injection. The open field, Y-maze, and Novel object tasks was used to assess learning and memory. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in the hippocampus also measured as markers of oxidative stress and inflammation. Furthermore, the expression of AQP-4 measured in the intact and experimental groups. ResultsThe results showed that Fasudil significantly improved memory and anxiety behavior induced by LPS in the open field maze, spatial recognition memory in the Y-maze, and performance in the novel object recognition task. It also mitigates hippocampal MDA and SOD levels. Additionally, fasudil ameliorated LPS-induced hippocampal levels of TNFα and IL-10 and increased hippocampal levels of AQP-4 expression in mice. ConclusionOur results suggest that fasudil in the LPS model of systemic inflammation could improve cognition by suppressing oxidative stress and inflammation and increasing AQP-4 protein expression. These findings highlighted the potential of fasudil as a neuroprotective agent. However, further research is required to fully understand its neuroprotective properties in the treatment of neurodegenerative disorders.

Effects of the Combination of Astragalus and Angelica on Cognitive and Memory Functions in Alzheimer's Disease Model Mice

This study aimed to investigate the effects of the combination of Astragalus and Angelica on cognitive and memory functions in Alzheimer’s disease (AD) model mice. Male ICR mice were divided into six groups: normal control, positive control (donepezil hydrochloride), model, and treatment groups (high, medium, and low doses of Astragalus-Angelica decoction), with six mice in each group. The AD model was established by administering D-galactose and sodium nitrite. Starting from the third week of modeling, the treatment groups received intragastric administration of 80, 40, and 20 mg/kg Astragalus-Angelica decoction, respectively, while the positive control group received 0.65 mg/kg donepezil hydrochloride via intragastric administration. On day 46 of the experiment, spontaneous alternation rate, novel object preference index, organ indices (brain, thymus, and spleen), malondialdehyde (MDA) content, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the hippocampus were measured. Results showed that, compared to the model group, the spontaneous alternation rates and novel object preference indices in all treatment groups were significantly increased (P<0.05), hippocampal MDA levels were significantly reduced (P<0.01), and SOD and GSH-Px activities were elevated (P<0.05). However, there were no significant differences in organ indices (P>0.05). These findings indicate that the Astragalus-Angelica decoction significantly improves impaired cognitive and memory functions in AD model mice, potentially through mechanisms involving enhanced antioxidant capacity in the hippocampus and mitigation of cellular aging.

Methane-rich saline ameliorates depressive-like behaviors during chronic unpredictable mild stress (CUMS).

Depression, considered the most prevalent neuropsychiatric disorder, is multifactorial and complex. Oxidative stress and inflammation significantly contribute to its etiology. Conversely, methane, a novel therapeutic gas, has demonstrated efficacy in enhancing tissue resilience against ischemic injuries and inflammation. In this study, we investigated the effect of methane-rich saline (MRS) on depression using the chronic unpredictable mild stress (CUMS) model. Depressed rats received MRS treatment, and depression-like behaviors and cognitive function were assessed through sucrose preference, open field, forced swimming, and Morris water maze tests. Additionally, we measured serum corticosterone levels, antioxidant enzyme activity, hippocampal malondialdehyde (MDA), and TNFα levels, and investigated histological changes in the hippocampus. Our findings revealed that MRS significantly ameliorated Depressive-like behaviors and cognitive impairment. Furthermore, MRS administration regulated serum corticosterone levels and also MRS reduced hippocampal lipid peroxidation, TNFα, and hippocampus tissue damage. MRS likely exerts its effects by reducing oxidative stress and inflammatory factors and modulating the function of the hypothalamus-pituitary-adrenal (HPA) axis. These results demonstrate the protective effects of MRS on the hippocampus in CUMS animals.

The Involvement of the Serotonergic System in Ketamine and Fluoxetine Combination-induced Cognitive Impairments in Mice.

Glutamatergic N-methyl-D-aspartate (NMDA) receptors play vital roles in memory formation. Changes in the activity of these receptors influence memory processes. Ketamine is a noncompetitive NMDA receptor antagonist drug with promising mood-altering and pain-reducing effects in low doses. These effects are believed to be related to altered serotonergic transmission. The present study investigated the involvement of the serotonergic system in low-dose ketamine administrations' effects on memory acquisition, consolidation, and retrieval processes. Sixty-four male BALB/c mice were used in this experiment and separated into 8t groups. Mice were treated subchronically with a selective serotonin reuptake inhibitor, fluoxetine, and a serotonin depletion agent, p-chlorophenylalanine (pCPA). A serotonin antagonist, methiothepin, and ketamine were acutely administered 60 minutes before or after the behavioral tests. A passive avoidance (PA) test measured emotional memory acquisition, consolidation, and retrieval processes. Hippocampi malondialdehyde (MDA) levels were analyzed, and histopathological examinations were performed. Ketamine alone did not significantly affect memory encoding processes in the PA test, while the ketamine-fluoxetine combination disrupted memory consolidation. Fluoxetine negatively affected the memory acquisition process, which was normalized during the consolidation and retrieval trials. Drug applications did not significantly alter hippocampal MDA levels. In all ketamine-applied groups, histopathologic alterations were evident. Low-dose ketamine administration induces neurodegeneration, and it also impairs memory functions when combined with fluoxetine, indicating increased serotonergic transmission may be involved in the memory-impairing and neurotoxic effects of ketamine.

Neuroprotective effects of g-Aminobutyric acid-enriched germinated riceberry extract in cerebral ischemic reperfusion-induced cognitive impairment mice

This study investigates the neuroprotective effects of riceberry (RB) and germinated riceberry (GRB) extracts on cognitive impairment induced by cerebral ischemia-reperfusion (IR) injury. Our findings indicate that the germination process reduces total phenolic content and total antioxidant capacity, accompanied by a decline in antioxidant activity. However, the enriched γ-aminobutyric acid (GABA) content significantly increased in the GRB extract, reaching an 11.55-fold higher concentration than the RB extract. Male ICR mice were used in this study and received RB (500 mg/kg BW) or GRB (250 and 500 mg/kg BW) extracts for 28 days, with cerebral IR injury induced on day 21. Memory and learning were assessed using the Morris water maze on days 22–27 and novel object recognition on day 28. Both RB and GRB extracts improved spatial and recognition memory while reducing hippocampal malondialdehyde levels, indicating decreased oxidative stress. GRB demonstrated superior effects, displaying accelerated learning responses and enhanced retention of spatial memory. The study highlights the potential of GRB, attributed to its high GABA content, in mitigating cognitive impairment induced by cerebral IR injury. Further research is needed to explore the underlying mechanisms and optimize therapeutic applications.

Capparis sepiaria’s root bark aqueous lyophilisate shows antiamnesic properties on scopolamine induce cognitive impairment in mice

Capparis sepiaria (Capparaceae) is a plant used in African traditional medicine to treat psychiatic disorders. The aim of this study was to assess the anti-amnesic effect of aqueous lyophilisate of the root bark of Capparis sepiaria (C. sepiaria) on scopolamine-induced animal model of memory impairment using Swiss albino adult mice of both sexes. Memory integrity was assessed by Morris water Maze test, Novel Object Recognition (NOR) and Object-location memory (OLT) tasks were used to assess behavioural components of memory processes and learning. Malondialdehyde (MDA), reduced glutathione (GSH), NO levels and catalase were used to assess oxidative stress while acethylcholinesterase activity was used to evaluate acetylcholine activity in the hippocampus tissues. The quantitative phytochemistry and acute toxicity of the roots of C. sepiaria were also evaluated. The aqueous lyophilisate of C. sepiaria at doses of 10 mg/kg and 40 mg/kg significantly increased the discrimination index in the Morris Water Maze and the objet location tasks. The aqueous lyophilisate of C. sepiaria significantly increased hippocampal GSH and catalase levels and decreased hippocampal MDA, NO levels and achetylcholinesterase (AChE) activities. The aqueous lyophilisate of C. sepiaria showed no acute toxicity with a LD50 > 5000 mg/kg, and revealed a content of flavonoids, tannins and phenols. These results suggest that C. sepiaria improve memory impairment induced by scopolamine and therefore possess antiamnesic properties. These properties would result from a modulation of cholinergic neurotransmission as well as an antioxidant activity of the plant.

Lipoic acid inhibits cognitive impairment induced by multiple cell phones in young male rats: role of Sirt1 and Atg7 pathway

The utilization of digital technology has grown rapidly in the past three decades. With this rapid increase, cell phones emit electromagnetic radiation; that is why electromagnetic field (EMF) has become a substantial new pollution source in modern civilization, mainly having adverse effects on the brain. While such a topic attracted many researchers’ scopes, there are still minimal discoveries made regarding chronic exposure to EMF. The extensive use of cell phones may affect children's cognition even indirectly if parents and guardians used their phones repeatedly near them. This study aims to investigate possible lipoic acid (LA) effects on cognitive functions and hippocampal structure in young male rats exposed to electromagnetic fields (EMF) emitted from multiple cell phones. Forty young male Wistar rats were randomly allocated into three groups: control, multiple cell phones-exposed and lipoic acid-treated rats. By the end of the experimental period, the Morris water maze was used as a cognitive test. The rats were sacrificed for the collection of serum and hippocampal tissue. These serum samples were then utilized for assessment of Liver function tests. The level ofglutamate, acetylcholine (Ach) and malondialdehyde (MDA) was estimated, in addition to evaluating the expression of autophagy-related protein-7 (Atg7) and Sirt1 genes. The left hippocampal specimens were used for histopathological studies. Results showed that multiple cell phone-exposed rats exhibited shorter latency time to reach the platform by the fifth day of training; additionally, there was a reduction in consolidation of spatial long-term memory. Correspondingly, there was an elevation of hippocampal Ach, glutamate, and MDA levels; accompanied by up-regulation of hippocampal Sirt1 and Atg7 gene expression. Compared to the EMF-exposed group, LA administration improved both learning and memory, this was proved by the significant decline in hippocampal MDA and Ach levels, the higher hippocampal glutamate, the downregulated hippocampal Sirt1 gene expression and the upregulated Atg7 gene expression. In conclusion, EMF exposure could enhance learning ability; however, it interfered with long-term memory consolidation shown by higher hippocampal Ach levels. Lipoic acid treatment improved both learning and memory by enhancing autophagy and hippocampal glutamate level and by the reduced Ach levels and Sirt1 gene expression.

Polysaccharides from Polygonatum cyrtonema Hua prevent post-traumatic stress disorder behaviors in mice: Mechanisms from the perspective of synaptic injury, oxidative stress, and neuroinflammation

Ethnopharmacological relevanceAccording to traditional Chinese medicine (TCM) theory, post-traumatic stress disorder (PTSD) is a kind of depression syndrome, and its occurrence is related to deficiencies of the heart and kidney. Polygonatum cyrtonema Hua replenishes Qi and blood and tonifies the five zang organs, so it is widely used in TCM as a prescription for the treatment of depression syndrome. The polysaccharides in P. cyrtonema Hua (PSP) are the main active components of the herb, but the effects of PSP on PTSD and the mechanisms remain unclear. Aim of the studyTo investigate the preventive effect of PSP on PTSD-like behaviors and to determine the mechanisms. MethodsWe used behavioral tests to evaluate PTSD-like behaviors in mice. Synaptic changes were assessed by transmission electron microscopy. Hematoxylin-eosin staining was used to assess pathological changes to the hippocampus, and immunofluorescence staining was used to observe changes in astrocytes. Serum corticosterone (CORT), cytokine, and hippocampal oxidation-related indicator levels were evaluated by ELISA. We detected the expression levels of synaptic, oxidative, and inflammation-related proteins in the hippocampus by western blotting. ResultsSingle prolonged stress (SPS)-modeled mice exhibited significant PTSD-like phenotypes, including increased fear memory acquisition and anxiety-like behaviors. These behavioral changes were prevented by PSP administration. Compared to controls, SPS modeling increased serum CORT, cytokine, and hippocampal malondialdehyde levels; decreased superoxide dismutase activity; and caused losses in pyramidal neurons, astrocytes, and synapses in the CA1 region. At the molecular level, the expression of brain-derived neurotrophic factor, postsynaptic density protein 95, nuclear factor erythroid 2-related factor 2 (Nrf2), phospho-tyrosine kinase receptor B, activity-regulated cytoskeleton-associated protein, heme oxygenase-1 (HO-1), and GluA1 decreased in SPS mice compared with the control group, while the expression of NOD-like receptor protein 3 (NLRP3), GluN2B, and apoptosis-associated speck-like protein increased in SPS mice. Treatment with PSP counteracted these abnormal changes. Importantly, ML385, an Nrf2 inhibitor, blocked PSP's ability to ameliorate PTSD behaviors and abnormal protein expression. The NLRP3 inhibitor MCC950 reduced the PTSD-like behaviors and normalized protein expression in SPS mice. ConclusionPSP prevents SPS-induced PTSD-like behaviors and synaptic damage by regulating oxidative stress and NLRP3-mediated inflammation, probably in an Nrf2/HO-1 signaling pathway-dependent manner.

Spotlight on Coenzyme Q10 in scopolamine-induced Alzheimer's disease: oxidative stress/PI3K/AKT/GSK 3ß/CREB/BDNF/TrKB.

Excess amyloid beta (Aβ) and oxidative stress (OS) are inextricable hallmarks of the neuronal damage associated Alzheimer's disease. Aβ-induced cognitive and memory dysfunctions are mediated through different signalling pathways as phosphatidylinositol-3-kinase (PI3K) and their downstream intermediates including protein-kinase-B, known as Akt, glycogen-synthase-kinase-3β (GSK-3β), cAMP-response-element-binding-protein (CREB), brain-derived-neurotrophic factor (BDNF) and tropomyosin-related-kinase receptor-B (TrKB). The current work aims to investigate the protective potentials of CoQ10 against scopolamine (Scop)-induced cognitive disability and the contribution of PI3K/Akt/GSK-3β/CREB/BDNF/TrKB in the neuroprotection effects. The chronic co-administration of CQ10 (50, 100 and 200 mg/kg/day i.p.) with Scop in Wistar rats for 6 weeks were assayed both behaviourally and biochemically. CoQ10 ameliorated the Scop-induced cognitive and memory defects by restoring alterations in novel object recognition and Morris water maze behavioural tests. CoQ10 favourably changed the Scop-induced deleterious effects in hippocampal malondialdehyde, 8-hydroxy-2' deoxyguanosine, antioxidants and PI3K/Akt/GSK-3β/CREB/BDNF/TrKB levels. These results exhibited the neuroprotective effects of CoQ10 on Scop-induced AD and revealed its ability to inhibit oxidative stress, amyloid deposition and to modulate PI3K/Akt/GSK-3β/CREB/BDNF/TrKB pathway.

Neuro-amelioration of Ficus lyrata (fiddle-leaf fig) extract conjugated with selenium nanoparticles against aluminium toxicity in rat brain: relevance to neurotransmitters, oxidative, inflammatory, and apoptotic events.

Aluminium is a non-essential metal, and its accumulation in the brain is linked with potent neurotoxic action and the development of many neurological diseases. This investigation, therefore, intended to examine the antagonistic efficacy of Ficus lyrata (fiddle-leaf fig) extract (FLE) conjugated with selenium nanoparticles (FLE-SeNPs) against aluminium chloride (AlCl3)-induced hippocampal injury in rats. Rats were allocated to five groups: control, FLE, AlCl3 (100mg/kg), AlCl3 + FLE (100mg/kg), and AlCl3 + FLE-SeNPs (0.5mg/kg). All agents were administered orally every day for 42days. The result revealed that pre-treated rats with FLE-SeNPs showed markedly lower acetylcholinesterase and Na+/K+-ATPase activities in the hippocampus than those in AlCl3 group. Additionally, FLE-SeNPs counteracted the oxidant stress-mediated by AlCl3 by increasing superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents in rat hippocampus. Besides, the formulated nanoparticles decreased the hippocampal malondialdehyde, carbonyl protein, and nitric oxide levels of AlCl3-exposed animals. Furthermore, FLE-SeNPs attenuated neural tissue inflammation, as demonstrated by decreased interleukin-1 beta, interleukin-6, nuclear factor kappa B, and glial fibrillary acidic protein. Remarkable anti-apoptotic action was exerted by FLE-SeNPs by increasing B cell lymphoma 2 and decreasing caspase-3 and Bcl-2-associated-X protein in AlCl3-exposed rats. The abovementioned results correlated well with the hippocampal histopathological findings. Given these results, SeNPs synthesized with FLE imparted a remarkable neuroprotective action against AlCl3-induced neurotoxicity by reversing oxidative damage, neuronal inflammation, and apoptosis in exposed rats.

Antidepressant-like effect of endogenous SO2 on depression caused by chronic unpredictable mild stress.

Sulfur dioxide (SO2) is a toxic gas with harmful effects on various organs. However, recent studies have confirmed the protective effect of SO2 on ischemic heart disease, atherosclerosis, and lung infections. Therefore, the present study was designed to investigate the effect of endogenous SO2 on depression. The chronic unpredictable mild stress (CUMS) model was performed to cause depression. Depression-like behaviors in animals were determined using an open-field test, forced swimming test, and sucrose consumption. Animal spatial learning and memory were also assessed using the Morris water maze. Besides, the oxidative status of the hippocampus and serum corticosterone level were evaluated. A reduction in the tendency to consume sucrose, mobility, and curiosity, as well as learning and memory disorders were observed in CUMS animals. Depressed animals treated with SO2 revealed a significant improvement in behavioral and cognitive functions. SO2 also reduced neuronal damage and lipid peroxidation of the hippocampus and serum corticosterone level in the CUMS group. Various shreds of evidence support a mutual relationship between inflammation and depression; also, growing studies show the role of oxidative stress in the pathogenesis of mood-related disorders such as depression. This study indicated that increased hippocampal malondialdehyde (MDA) and serum corticosterone levels can be due to the existence of oxidative stress and possible activation of inflammatory processes. SO2 donors diminished MDA and corticosterone levels in depressed animals. According to the study results, SO2 may be able to reduce tissue damage and eventually behavioral disorders caused by depression by lowering oxidative stress and inflammation.

The effect of ghrelin on antioxidant status in the rat's model of Alzheimer's disease induced by amyloid-beta.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with amyloid-beta (Aβ) plaque formation and oxidative stress in the brain. Ghrelin has been proven to exert antioxidant activity and neuroprotection in different neurological diseases. This study is going on to examine the effect of ghrelin on antioxidant status in the rat's model of AD induced by Aβ. Cognitive impairment was induced by intra-hippocampal administration of Aβ (10 μg) in Wistar rats and ghrelin (80 μg/kg) was administrated intraperitoneal for ten consecutive days. Behavior was assessed with Morris water maze and passive avoidance tests. Malondialdehyde (MDA) level as a marker of lipid peroxidation was assessed using the thiobarbituric acid. Catalase activity was assayed by the decomposition of H2O2. Antioxidant capacity was determined using the FRAP method. Treatment with ghrelin decreased the hippocampus and serum MDA levels in wild-type rodents and prevented an increase in hippocampal and serum MDA levels in animals receiving Aβ. There was no significant change in the serum catalase activity between the studied groups. Hippocampus catalase activity was reduced in the Aβ group and treatment with ghrelin increased it. The antioxidant capacity of the hippocampus and serum increased in the ghrelin-receiving control group. The hippocampus antioxidant capacity level decreased in the Aβ group, and treatment with ghrelin increased it, but there were no significant changes in the serum antioxidant capacity of animals receiving Aβ. These results provide evidence that the administration of ghrelin has antioxidant properties and protects against hippocampal lipid peroxidation in a rat model of AD.

Comparison of the effect of glyphosate and glyphosate-based herbicide on hippocampal neurogenesis after developmental exposure in rats

Increasing evidence indicates that glyphosate (GlyP)-based herbicides (GBHs) induce developmental neurotoxicity. The present study investigated the developmental exposure effect of GlyP and GBH on hippocampal neurogenesis in rats. Dams were treated from gestational day 6 to day 21 post-delivery on weaning with a diet containing 1.5% or 3.0% GlyP or drinking water with 1.0% GBH (containing 0.36% GlyP). Dams in the 1.5%-GlyP, 3.0%-GlyP, and GBH groups received 1.04, 2.16, and 0.25 g GlyP/kg body weight (BW)/day during gestation, and 2.27, 4.65, and 0.58 g GlyP/kg BW/day during lactation, respectively. On weaning, 3.0% GlyP- and GBH-exposed offspring decreased the BW, and the latter also decreased the brain weight. Both compounds suppressed neural progenitor cell proliferation in the neurogenic niche, and GlyP-exposed offspring showed a decreased number of TUBB3+ immature granule cells. In contrast, both compounds increased the number of ARC+ granule cells, suggesting increased synaptic plasticity. Both compounds downregulated antioxidant genes (Cat and Sod2) in the dentate gyrus, suggestive of increased sensitivity to oxidative stress, which might be related to the suppression of neurogenesis. At the adult age, GBH alone sustained decreases in body and brain weights. Both compounds increased hippocampal malondialdehyde levels and upregulated Cat in the dentate gyrus, suggesting induction of oxidative stress. Both compounds upregulated Casp9, and GBH increased neural progenitor cell apoptosis, suggesting disruption of neurogenesis related to oxidative stress. GBH increased the number of COX2+ granule cells, and both compounds upregulated Arc, suggesting increased synaptic plasticity. These results suggest that GlyP and GBH might cause similar effects on disruption of neurogenesis accompanying compensatory responses and induction of oxidative stress responses through the adult age in the hippocampus. However, effects on adult age were more evident with GBH, suggesting that the surfactants contained in GBH might have contributed to the enhanced neurotoxicity of GlyP, similar to the enhanced general toxicity.

Fenofibrate Improves Cognitive Impairment Induced by High-Fat High-Fructose Diet: A Possible Role of Irisin and Heat Shock Proteins.

A high-fat, high-fructose diet (HFFD) impairs cognitive functions and increases susceptibility to neurodegenerative disorders. Irisin and heat shock protein 70 (HSP70) are well known for their role in neuroprotection. The possible neuroprotective effects of fenofibrate on HFFD-induced cognitive dysfunction and the involvement of irisin and HSP70 in these effects were investigated in this study. Rats were divided into normal control, HFFD, dimethylsulfoxide+HFFD, and fenofibrate+HFFD groups. At the end of the experiment, fenofibrate treatment restored hippocampus histological characteristics to almost normal and improved HFFD-induced cognitive deficit. It reduced body weight gain and had hypolipidemic effects by significantly lowering total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels while increasing high-density lipoprotein cholesterol levels. It has antioxidant and anti-inflammatory effects as it significantly reduced the hippocampal malondialdehyde, interleukin-6, and tumor necrosis factor-alpha levels, while significantly increasing the reduced glutathione level. It prevented HFFD-induced hypoxia by significantly lowering hippocampal vascular endothelial growth factor and hypoxia-inducible factor-1 alpha levels. It significantly activated the hippocampal peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α)/irisin/brain-derived neurotrophic factor pathway. It significantly increased hippocampal HSP70 while decreasing the HSP90 levels. It enhanced synaptic plasticity by significantly upregulating the hippocampal relative GluR1 gene expression. Furthermore, hippocampal irisin levels in the HFFD group were found to be positively correlated with cognitive function, hippocampal HSP70, and relative GluR1 gene expression levels, while negatively correlated with hippocampal HSP90 and HIF1α levels. Therefore, fenofibrate may be used as a potential medication to treat HFFD-induced neurodegenerative disorders.

Risperidone and ethyl pyruvate have protective effects against ketamine-induced cognitive impairments in mice.

Ketamine, an N-methyl D-aspartic acid receptor antagonist drug, is reported to produce memory disruptions. The aim of this study was to investigate the protective effects of ethyl pyruvate (EP), a pyruvic acid derivative, and risperidone, an atypical antipsychotic drug, against ketamine-induced cognitive disturbances. A passive-avoidance test, a novel object recognition test, and a modified elevated plus maze test were used to assess memory functions. Hippocampal malondialdehyde (MDA) levels were measured to determine the oxidation levels. Ketamine applications produced memory deficits in all tests and insignificantly increased MDA levels, which were alleviated by risperidone, EP, and combination treatments. Increased oxidative stress and neurotransmission imbalance can be responsible for ketamine-induced memory disruptions. With its antioxidant effects, EP may be helpful to reduce cognitive impairments related to schizophrenia either alone or in combination with antipsychotics.

Impaired memory by hippocampal oxidative stress in rats exposed to 900 MHz electromagnetic fields is ameliorated by thymoquinone

The protective effects of thymoquinone on learning and memory abilities and on hippocampal oxidative stress in rats exposed to 900 MHz electromagnetic field radiation at s strength of 6.0 ± 0.5 V/m for 1 h on each of 15 days was studied. Thymoquinone-treatment (10 mg/kg/day) of radiation-exposed rats resulted in better performance than that of radiation-exposed rats not receiving thymoquinone. Electromagnetic field-exposure led to increased hippocampal superoxide dismutase, glutathione peroxidase, and malondialdehyde levels and to lowered brain-derived neurotrophic factor level; thymoquinone treatment ameliorated all four parameters. Also, in the electromagnetic field-exposed group, N-methyl-D-aspartate receptor expression decreased, and gamma-aminobutyric-acid alpha receptor expression increased, which was reversed by thymoquinone treatment. In conclusion, treatment with the thymoquinone ameliorated the impact of the exposure to EMF and provided a hint on the mechanism involving oxidative stress.

Assessment of lipophilic fluorescence products in β-amyloid-induced cognitive decline: A parallel track in hippocampus, CSF, plasma and erythrocytes.

Oxidative stress implicates in Alzheimer's disease (AD) pathophysiology, and associates with the creation of end products of free radical reactions, are known as lipophilic fluorescent products (LFPs). This study aimed to evaluate the probable parallel alterations in the spectral properties of the LFPs in the hippocampus tissues, cerebrospinal fluid (CSF), plasma, and erythrocytes during AD model induction by intra-cerebroventricular (ICV) amyloid β-protein fragment 25-35 (Aβ) injection. Male rats received an intra-ICV injection of Aβ. Hippocampus, CSF, plasma, and erythrocytes were harvested at 5, 14, and 21days after Aβ injection. The fluorescent intensity of LFPs was assessed by spectrofluorimetry using synchronous fluorescence spectra 25 (SYN 25) and 50 (SYN 50) in the range of 250-500nm. Hippocampal tissue malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured. Cognitive alterations were evaluated using Morris water maze (MWM) test. The parallel significant rise in the fluorescence intensity of LFPs was detected in the hippocampus, CSF, plasma, and erythrocytes, 14, and 21days after ICV-Aβ injection. These alterations were found in both types of synchronous spectra 25, and 50, and were coincided with hippocampal cognitive decline, the MDA rise, and decrease of SOD activity. There was a positive correlation between hippocampus homogenate, and plasma or CSF rise in fluorescence intensity. Data showed that the Aβ increased hippocampal MDA, and decreased SOD activity, led to a higher rate of oxidative products and subsequently resulted in an increase in LFPs fluorescence intensity during the development of cognitive decline. LFPs' alterations reflect a comprehensive view of tissue redox status. The fluorescence properties of LFPs indicate their composition, which may pave the way to trace the different pathological states.

Mesenchymal stem cells after the proprocessing of tanshinone IIA attenuate cognitive deficits and oxidative stress injury in an amyloid β-peptide (25-35)-induced rodent model of Alzheimer's disease.

To verify whether mesenchymal stem cells cocultured with tanshinone IIA may ameliorate Alzheimer's disease by inhibiting oxidative stress. Sixty male Sprague-Dawley rats were randomly divided into 4 groups named Sham, Aβ25-35, mesenchymal stem cells, and mesenchymal stem cells (tanshinone IIA). The rats were treated according to different groups. The neurobehavioral performance of Sprague-Dawley rats was evaluated via Morris water maze test. Histological changes were checked via hematoxylin-eosin staining. The levels of total antioxidant activity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malondialdehyde in hippocampus were assayed by ELISA kit. The levels of Aβ, p-tau/tau, and p-AMP-activated protein kinase/AMP-activated protein kinase in hippocampus were checked by Western blot. Our research showed that the injection of mesenchymal stem cells (tanshinone IIA) into the hippocampus alleviated learning and memory deficits and reduced hippocampal neuronal injury in the Alzheimer's disease rats. Moreover, mesenchymal stem cells (tanshinone IIA) treatment suppressed oxidative stress, attenuated Aβ accumulation reduced Tau hyperphosphorylation, and enhanced the activity of AMP-activated protein kinase in the hippocampus of the Alzheimer's disease rats. However, there were almost no significant difference between the mesenchymal stem cells and Aβ25-35 groups. Mesenchymal stem cells (tanshinone IIA) transplantation may be a potential treatment for curing Alzheimer's disease, which may be related to the inhibition of oxidative stress.

Effect of Continuous and Interval Training on Amyloid β 42 (Aβ42) and Malondialdehyde (MDA) Levels in Hippocampus of Elderly Rats

Introduction: Amyloid plaques in the brain increase with age. Thus, the present study aimed to evaluate the effect of continuous and interval training on Amyloid β 42 (Aβ42) and Malondialdehyde (MDA) levels in hippocampus of elderly rats. Methods: The present study was experimental one with two experimental groups and one control group. Thirty old male Wistar rats (18 weeks-old) divided into 3 groups, including interval training, continuous training, and control. Continuous training was performed for 8 weeks with 65 to 70% VO2max and interval training was performed for 8 weeks with 5-8 repetitions of 2 minutes of working with 80-100% VO2max and 2 minutes active rest with 50% of VO2max for 8 weeks. Hippocampal samples were extracted 48 hours after the last training session to measure protein levels of Aβ42 and MDA. One-way ANOVA and Tukey post hoc test was used for data analysis. Results: Hippocampus Aβ42 levels in continuous training groups were significantly lower than the control group (P=0.001). In addition, Aβ42 levels in hippocampus of interval training groups were significantly lower than the control group (P=0.001). However, no significant differences were found in Aβ42 levels between continuous and interval training groups (p=0.502). MDA levels in continuous training groups were significantly lower than the control group (P=0.016). In addition, MDA levels in interval training groups were significantly lower than the control group (P=0.046) But no significant differences were found in hippocampal MDA protein levels between continuous and interval training groups (p=866). Conclusion: Continuous and interval training through decreasing oxidative stress, decrease Aβ42 levels in the hippocampus of the elderly rat, thus probably continuous and interval training can prevent neurodegenerative disease caused by aging through modulating oxidative stress and Aβ42.

Zingiber officinale (Ginger) hydroalcoholic extract improved avoidance memory in rat model of streptozotocin-induced diabetes by regulating brain oxidative stress.

Diabetes mellitus associated cognitive impairment is suggested to be due to oxidative stress. Considering the anti-diabetic, antioxidant, antihyperlipidemic, and anti-inflammatory effects of Zingiber officinale, the present study aimed to investigate its effect on memory and oxidative stress factors in streptozotocin (STZ)-induced diabetic rats. The rats were allocated into five groups: Control, Diabetic, Diabetic+Ginger 100, Diabetic+Ginger 200, and Diabetic+Ginger 400. Following diabetes induction by STZ (60mg/kg), 100, 200, or 400mg/kg Ginger was given for eightweeks. Passive avoidance test (PA) was done and thiol, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) measurements were carried out in the brain. The latency into the dark compartment decreased (p<0.001) and the number of entries and time spent in the dark chamber increased in the Diabetic group compared to the Control (p<0.001 for all). All three doses of extract improved performance of the rats in the PA test (p<0.001 for all). The hippocampal and cortical MDA level was higher (p<0.001) while CAT, SOD, and total thiol were lower (p<0.01-p<0.001) in the Diabetic group than the Control. Treatment with 200 and 400mg/kg Z.officinale extract reduced hippocampal and cortical MDA (p<0.001) and improved CAT (p<0.001) while, just the dose of 400mg/kg of the extract increased SOD and total thiol in hippocampal and cortical tissues (p<0.001) compared with Diabetic group. Z.officinale extract could improve memory by reducing the oxidative stress in STZ-induced diabetes model.