scholarly journals Dimethyl fumarate prevents acute lung injury related cognitive impairment potentially via reducing inflammation

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xiaowei Wang ◽  
Yanbo Wang ◽  
Haiyan Pan ◽  
Ci Yan
Keyword(s):  
Cognitive Impairment ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Water Maze ◽  
Dimethyl Fumarate ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Maze Test ◽  
Evans Blue Extravasation ◽  
Brain Tissues

Abstract Objective Dimethyl fumarate (DMF) has been reported to exert a protective role against diverse lung diseases and cognitive impairment-related diseases. Thus this study aimed to investigate its role on acute lung injury (ALI) and related cognitive impairment in animal model. Methods C57BL/6 mice were divided into four groups: control group, DMF group, ALI group, and ALI + DMF group. For ALI group, the ALI mice model was created by airway injection of LPS (50 μL, 1 μg/μL); for ALI + DMF group, DMF (dissolved in 0.08% methylcellulose) was treated twice a day for 2 days, and on the third day, mice were injected with LPS for ALI modeling. Mice pre-administered with methylcellulose or DMF without LPS injection (PBS instead) were used as the control group and DMF group, respectively. Morris water maze test was performed before any treatment (0 h) and 6 h after LPS-induction (54 h) to evaluate the cognitive impairment of mice. Next, the brain edema and blood brain barrier (BBB) permeability of ALI mice were assessed by brain water content, Evans blue extravasation and FITC-Dextran uptake assays. In addition, the effect of DMF on the numbers of total cells and neutrophils, protein content in BALF were quantified; the inflammatory factors in BALF, serum, and brain tissues were examined by ELISA, qRT-PCR, and Western blot assays. The effect of DMF on the cognitive impairment-related factor HIF-1α level in lung and brain tissues was also examined by Western blot. Results DMF reduced the numbers of total cells, neutrophils and protein content in BALF of ALI mice, inhibited the levels of IL-6, TNF-α and IL-1β in BALF, serum and brain tissues of ALI mice. The protein expressions of p-NF-κB/NF-κB and p-IKBα/IKBα was also suppressed by DMF in ALI mice. Morris water maze test showed that DMF alleviated the cognitive impairment in ALI mice by reducing the escape latency and path length. Moreover, DMF lessened the BBB permeability by decreasing cerebral water content, Evans blue extravasation and FITC-Dextran uptake in ALI mice. The HIF-1α levels in lung and brain tissues of ALI mice were also lessened by DMF. Conclusion In conclusion, DME had the ability to alleviate the lung injury and cerebral cognitive impairment in ALI model mice. This protective effect partly associated with the suppression of inflammation by DMF.

Acupuncture Improves Cognitive Deficits and Increases Neuron Density of the Hippocampus in Middle-Aged Samp8 Mice

2012 ◽  
Vol 30 (4) ◽  
pp. 339-345 ◽  
Author(s):  
Guomin Li ◽  
Xuezhu Zhang ◽  
Haiyan Cheng ◽  
Xuemei Shang ◽  
Hui Xie ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Morris Water Maze ◽  
Cognitive Deficits ◽  
Water Maze ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Neuron Loss ◽  
Neuron Density ◽  
Maze Test ◽  
Samp8 Mice

Objectives To examine whether acupuncture could improve cognitive deficits and reduce the loss of neurons in mice models of ageing. Methods Male 7.5-month-old senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-resistant inbred strains 1 (SAMR1) were divided into four groups (n=15 per group): SAMP8 acupuncture group (Pa), SAMP8 non-acupuncture point control group (Pn), SAMP8 control group (Pc) and SAMR1 normal control group (Rc). The behaviours were examined by the Morris water maze test and the neuron density in the hippocampus was estimated by the optical fractionator technique. Results The Morris water maze test demonstrated that the cognitive deficits of SAMP8 mice were improved by acupuncture treatment. Neuronal loss was found in hippocampal regions CA1 (−24%), CA3 (−18%) and DG (−28%) of Pc compared with Rc. The neuron number in hippocampal CA3 and DG of the Pa group was significantly increased by therapeutic acupuncture compared with the Pc group. Conclusions Acupuncture improved the cognitive impairment of middle-aged SAMP8 mice which could be attributed to the reduced neuron loss in hippocampal regions CA3 and DG. These results suggest that reducing neuron loss in the hippocampus by acupuncture is a potential therapeutic approach for the treatment of Alzheimer's disease and cognitive impairment diseases.

scholarly journals Dexmedetomidine Attenuates Neurotoxicity in Developing Rats Induced by Sevoflurane through Upregulating BDNF-TrkB-CREB and Downregulating ProBDNF-P75NRT-RhoA Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Yunxia Dong ◽  
Wei Hong ◽  
Zhiyin Tang ◽  
Yan Gao ◽  
Xiuying Wu ◽  
...  
Keyword(s):  
Normal Saline ◽  
Water Maze ◽  
Escape Latency ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Sprague Dawley ◽  
Sevoflurane Group ◽  
Maze Test ◽  
Sprague Dawley Rats ◽  
Rhoa Signaling

To investigate the mechanism dexmedetomidine in relieving the neurotoxicity of a developing brain induced by sevoflurane. Sprague-Dawley rats, 6 days old, were randomly divided into three groups. Rats in the control group were inhaled with air after injection of normal saline; rats in the sevoflurane group were injected with normal saline and inhaled with 3% sevoflurane for 2 h in three consecutive day; rats in the dexmedetomidine group were inhaled with 3% sevoflurane after intraperitoneal injection of dexmedetomidine 25 μg/kg. WB results showed that mBDNF, pTrkB/TrkB, and CREB were significantly decreased in the hippocampus of the sevoflurane group, which are significantly upregulated in the dexmedetomidine group. In the sevoflurane group, proBDNF, P75NRT, and RhoA were significantly increased, which were significantly lower than those in the dexmedetomidine group than those in the sevoflurane group. The expression BDNF was downregulated in the sevoflurane group, while the proBDNF was upregulated in the sevoflurane group. In the Morris water maze test, the escape latency of the sevoflurane group was significantly prolonged. In sevoflurane groups, the number of crossing platform was significantly reduced, the synaptic protein decreased significantly, and this effect was reversed in rats of the dexmedetomidine group. Dexmedetomidine could reduce synaptic plasticity decline in developing rats induced by sevoflurane, through downregulating the proBDNF-p75NTR-RhoA pathway and upregulating BDNF-TrkB-CREB.

scholarly journals Effect of Nyctanthes arbor tristis leaf extract against scopolamine-induced cognitive impairment in rats

2015 ◽  
Vol 60 (4) ◽  
pp. 34-49
Author(s):  
Bashetty Phanindhra ◽  
Akondi Butchi Raju ◽  
Gadiyaram Vikas ◽  
Repala Anusha ◽  
Donapati Deepika
Keyword(s):  
Cognitive Impairment ◽  
Protective Effect ◽  
Morris Water Maze ◽  
Water Maze ◽  
Active Avoidance ◽  
Ethanol Extract ◽  
Thiobarbituric Acid ◽  
Morris Water Maze Test ◽  
Radial Arm Maze ◽  
Maze Test

Summary Nyctanthes arbor tristis (NATE) ethanol extract (150 mg/kg, orally) was evaluated for its protective effect against scopolamine-induced (1 mg/kg i.p.) cognitive impairments in rats using behavioral models like radial arm maze test, Morris water maze test and active avoidance test. NATE effect was evaluated and compared with the standard piracetam (200mg/kg i.p.). NATE (p<0.005) significantly reversed the impairment produced by the scopolamine in radial arm maze test. In addition, NATE also decreased the time period taken to find the hidden platform in Morris water maze test and increased number of avoidances in active avoidance paradigm. Acetylcholinesterase activity and thiobarbituric acid levels were significantly (p<0.005) decreased along with the rise in activities of superoxide dismutase and catalase. This might suggest that the NATE has protective effect against scopolamine-induced cognitive impairment in rats through acetylcholine muscarinic receptor pathway and also antioxidant activity. No significant changes were found in histopathological studies of brain.

Yam (Dioscorea pseudojaponica Yamamoto) Ameliorates Cognition Deficit and Attenuates Oxidative Damage in Senescent Mice Induced by D-Galactose

2009 ◽  
Vol 37 (05) ◽  
pp. 889-902 ◽  
Author(s):  
Chuan-Sung Chiu ◽  
Jeng-Shyan Deng ◽  
Ming-Tsuen Hsieh ◽  
Ming-Jen Fan ◽  
Min-Min Lee ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Cognitive Impairment ◽  
Learning And Memory ◽  
Morris Water Maze ◽  
Water Maze ◽  
Neuroprotective Effect ◽  
Morris Water Maze Test ◽  
Maze Test ◽  
Mice Brain ◽  
Endogenous Antioxidant

This study attempted to access the neuroprotective effect of yam (Dioscorea pseudojaponica Yamamoto) on the senescent mice induced by D-gal. The mice in the experiments were administered orally with yam (20, 100 or 500 mg/kg for 4 weeks, from the sixth week). The learning and memory abilities of the mice in Morris water maze test and the mechanisms involved in the neuroprotective effect of yam on the mice brain tissue were investigated. The content of diosgenin in the yam was also detected by using HPLC. Mice treated with yam were found to significantly improve their learning and memory abilities in Morris water maze test compared to those treated with D-gal (200 mg/kg for 10 weeks). In addition, yam was also found to increase the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and decrease the malondialdehyde (MDA) level on the brains of D-gal treated mice. Finally, the amount of diosgenin in the yam was 5.49 mg/g extract. To sum up, these results indicate that yam had the potential to be a useful treatment for cognitive impairment in TCM. Its beneficial effect may be partly mediated via enhancing endogenous antioxidant enzymatic activities.

Scutellarin Ameliorates Learning and Memory Deficit via Suppressing β-Amyloid Formation and Microglial Activation in Rats with Chronic Cerebral Hypoperfusion

2018 ◽  
Vol 46 (06) ◽  
pp. 1203-1223 ◽  
Author(s):  
Jung-Won Shin ◽  
Ki-Jung Kweon ◽  
Dong-Kyu Kim ◽  
Pyungsoo Kim ◽  
Tae-Dong Jeon ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Microglial Activation ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Amyloid Formation ◽  
Amyloid A ◽  
Text Formation ◽  
Brain Tissues

Chronic cerebral hypoperfusion is considered as a pivotal factor of cognitive impairment that occurs in cerebrovascular diseases. This study investigated the ameliorating effect of scutellarin (SCT) on spatial cognitive impairment and [Formula: see text]-amyloid (A[Formula: see text]) formation in rats with chronic cerebral hypoperfusion induced by permanent bilateral common carotid artery occlusion (pBCAO). SCT is a flavonoid in medicinal herb of Erigeron breviscapus (vant.) Hand. Mazz. known to have neuroprotective, antioxidative and anti-inflammatory effects. However, the beneficial effect and pivotal mechanism of SCT on cognitive impairment are still unclear. SCT was treated orally with two doses (10 or 30[Formula: see text]mg/kg) for 4 weeks. Results of Morris water maze test performed on the ninth week after pBCAO revealed that SCT (30[Formula: see text]mg/kg)-treated rats had significantly shortened escape latencies in acquisition training trials, significantly prolonged swimming time at the platform and its surrounding zone, significant increase in memory score, significant reduction in the number of target heading, and significant reduction in the time required for the first target heading during the retention trial compared to rats in the sham-control group. SCT significantly inhibited the production of A[Formula: see text] and A[Formula: see text] in brain tissues. However, SCT significantly upregulated the expression levels of amyloid precursor protein and [Formula: see text]-site APP-converting enzyme-1 in the hippocampus. In addition, SCT significantly inhibited the activation of Iba1-expressing microglia in brain tissues. The results suggest that SCT can exert ameliorating effect on spatial cognitive impairment caused by chronic cerebral hypoperfusion through suppressing A[Formula: see text] formation and microglial activation in brain tissues. Therefore, SCT can be used as a beneficial drug for vascular dementia and Alzheimer’s disease.

scholarly journals Electroacupuncture Synergistically Inhibits Proinflammatory Cytokine Production and Improves Cognitive Function in Rats with Cognitive Impairment due to Hepatic Encephalopathy through p38MAPK/STAT3 and TLR4/NF-κB Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Jiling Huang ◽  
Zhigang Gong ◽  
Yingnan Kong ◽  
Yanwen Huang ◽  
Hui Wang ◽  
...  
Keyword(s):  
Hepatic Encephalopathy ◽  
Brain Tissue ◽  
Water Maze ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Model Group ◽  
Maze Test ◽  
Tnf Α ◽  
Serum Ammonia ◽  
The Brain

Objective. To investigate the effect of electroacupuncture (EA) on cognitive dysfunction in rats with hepatic encephalopathy and its underlying mechanism. Methods. Fifty Wistar rats were randomly divided into a normal group (n = 10) and model group (n = 40). Rat models of hepatic encephalopathy were established by administration of carbon tetrachloride and thioacetamide for a total of 12 weeks. At the 9th week after modeling, rats with cognitive impairment in the model group were identified by conducting the Morris water maze test, which were then randomly divided into a control group (CCl4) and treatment groups including EA group (CCl4 + EA), lactulose group (CCl4 + Lac), and EA plus lactulose group (CCl4 + CM), with 9 rats in each group. At the end of the 9th week, rats in CCl4 + Lac and CCl4 + CM groups had lactulose gavage at a dose of 10 mL/kg body weight, while normal control and CCl4 groups had gavage with the same volume of normal saline once a day for 21 days until the end of the experiment. Rats in CCl4 + EA and CCl4 + CM groups underwent acupuncture at Baihui (GV[DU]20), Shenting (GV[DU]24), and Zusanli (ST36) acupoints, among which EA at Baihui and Shenting acupoints were given once daily for 30 min lasting for 21 consecutive days. The effect of the treatment was measured by the Morris water maze test for learning and memory ability and magnetic resonance spectroscopy (MRS) for neuronal metabolism in the hippocampus of rats with hepatic encephalopathy. Pathological change in the rat hippocampus was observed by HE staining, while serum ammonia and liver function markers were detected. Western blot and real-time fluorescent quantitative PCR were used to detect the expressions of specific genes and proteins in the brain tissue. Results. Compared with those in the control group, rats undergoing EA had significantly shortened escape latency and increased number of platform crossing. H&E staining confirmed that EA improved brain tissue necrosis and ameliorated nuclear pyknosis in rats with hepatic encephalopathy. Significantly decreased levels of serum ammonia, alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), and total bile acid (TBA) were observed in rats undergoing EA, as well as improved levels of total protein (TP) and albumin (ALB). In addition, EA inhibited the brain expressions of TNF-α, IL-1β, IL-6, iNOS, TLR4, MyD88, NF-κB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-α, IL-6, TLR4, MyD88, NF-κB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3. MRS showed increased Glx/Cr and decreased NAA/Cr, Cho/Cr and mI/Cr in the control group, and EA significantly reversed such changes in Glx/Cr and mI/Cr values. Conclusion. EA ameliorated the production of excessive proinflammatory cytokines in the hippocampus of rats with cognitive dysfunction secondary to hepatic encephalopathy, which also gave rise to subsequent changes such as reduced blood ammonia level, brain-protective activated astrocytes, and lower degree of brain tissue injury. The p38MAPK/STAT3 and TLR4/MyD88/NF-κB signaling pathways may be involved. EA can also improve the metabolism of NAA and Cho in the rat hippocampus and thereby improve learning and memory abilities.

scholarly journals Impact of amitriptyline on learning and memory

2021 ◽  
Vol 5 (1) ◽  
pp. 009-015
Author(s):  
CC Mfem ◽  
SA Seriki
Keyword(s):  
Learning And Memory ◽  
Morris Water Maze ◽  
Acquisition Trial ◽  
Water Maze ◽  
Treated Group ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Maze Test ◽  
Significant Difference ◽  
Retention Trial

Background/aim: Amitriptyline belongs to class of known as tricycline antidepresant (TCA) that is being used to treat anxiety and depressive states. It may help improve mood and feelings of well-being, relieve anxiety and tension, help to improve sleep and increase energy level. The study investigated the effect of amitriptyline on learning and memory using eighteen (18) healthy Swiss mice of both sexes weighing 16 – 25 g. Method: The animals were divided into three (3) groups consisting of six (6) animals each. Group 1 served as the control group, Group 2 was administered with amitriptyline at a dose of 3 mg/kg body weight dissolved in 3 mls of distilled water, and used to test for learning, while Group three was also given similar administration like Group 2, but used to test for memory. All the animals were tested for learning and memory performance using Novel object recognition task and Morris water maze test. Results: The results obtained from the Novel object recognition task showed that there was a significant decrease (p < 0.05) in total object approach in acquisition trial of amitriptyline treated group when compared to the acquisition trial of the control group. There was a significant decrease (p < 0.05) in retention trial of amitriptyline group when compared to retention trial in the control group. There was a significant decrease (p < 0.05) in total duration exploring objects in acquisition trial of amitriptyline treated group when compared to the acquisition trial of the control group. There was a significant increase (p < 0.05) in total duration exploring objects in retention trial of amitriptyline treated group when compared to the retention trial of the control group. There was a significant decrease (p < 0.05) in the index of habituation of amitriptyline treated group when compared to the control group. The index of discrimination showed a significant increase (p < 0.05) in amitriptyline treated group when compared to the control group and a significant decrease (p < 0.05) in amitriptyline group when compared to the control group. In the Morris water maze test, Day 1 – 3 were for acquisition training, day 4 – 6 reversal training, day 7 the probe trial day and day 8 the visible platform day. During acquisition training in the Morris water maze test, there was no significant difference in Swim latencies in day 1 and 2. However in day 3, there was a significant increase (p < 0.05) in swim latency of group compared to control group and a significant decrease (p < 0.05) in swim latency of amitriptyline treated group compared to the control group. During reversal training in day 1, 2 and 3, there was no significant difference in swim latency among the three groups. Results for the retention quadrant in the probe trials showed a significant decrease (p < 0.01) in amitriptyline group when compared to the control group. Conclusion: Results suggest that amitriptyline impairs learning and memory functions.

Isoflurane-induced miR-140-5p aggravates neurotoxicity in diabetic rats by targeting SNX12

2019 ◽  
Vol 16 ◽  
Author(s):  
Dongyi Fan ◽  
Simin Yang ◽  
Yuxiang Han ◽  
Ru Zhang ◽  
Lukun Yang
Keyword(s):  
Cognitive Impairment ◽  
Morris Water Maze ◽  
Water Maze ◽  
Neuroprotective Effect ◽  
Diabetic Rats ◽  
Morris Water Maze Test ◽  
Maze Test ◽  
Luciferase Activity Assay ◽  
Novel Target ◽  
Isoflurane Treatment

Objectives: MicroRNAs (miRNAs) are widely known as critical regulators in isoflurane-induced neurotoxicity during the development of brain. Isoflurane could aggravate cognitive impairment in diabetic rats. The present study was designed to explore the role and mechanism of miR-140-5p on isoflurane-induced neurotoxicity in diabetic rats. Methods: Diabetic rats model was established by injection of streptozotocin (STZ) and identified by Morris water maze test. Expression of miR-140-5p in diabetic rats under isoflurane treatment was evaluated via qRT-PCR (quantitative real-time polymerase chain reaction). Latency to platform and time spent in the target quadrant were calculated to detect the effect of miR-140-5p on neurotoxicity. The potential target for miR-140-5p was validated via dual luciferase activity assay. Results: Morris water maze test indicated that isoflurane treatment exacerbated STZ-induced cognitive impairment, as demonstrated by increase of latency to platform and decrease of time spent in the target quadrant. MiR-140-5p was up-regulated in diabetic rats under isoflurane treatment. Moreover, knockdown of miR-140-5p attenuated neurotoxicity in diabetic rats. Mechanistically, we found that miR-140-5p could directly bind to SNX12 (sorting nexin 12). The neuroprotective effect of miR-140-5p against isoflurane-aggravated neurotoxicity in diabetic rats dependent on up-regulation of SNX12 and inhibition of cell apoptosis. Conclusions: Knockdown of miR-140-5p relieved isoflurane-aggravated neurotoxicity in diabetic rats through targeting SNX12, suggesting a novel target for neuroprotection in diabetes under isoflurane treatment.

Improvement of Impaired Memory in Mice by Schisandrin

2013 ◽  
Vol 750-752 ◽  
pp. 1533-1538
Author(s):  
Yan Chun Wang ◽  
Kuang Ren ◽  
Nan Shen ◽  
Xiao Dong Huang ◽  
Hong Yan Fan
Keyword(s):  
Learning And Memory ◽  
Morris Water Maze ◽  
Water Maze ◽  
Memory Impairment ◽  
Cellular Response ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Tissue Samples ◽  
Pentobarbital Sodium ◽  
Maze Test

We assessed the effectiveness and mechanism of action of schisandrin on modulation of learning and memory disorders in mice. Memory impairment was established in mice by intraperitoneal injection of pentobarbital sodium (20 mg/kg). Schisandrin (0.5, 1.0, 2.0g/kg) were administered by intragavage once daily for 14 consecutive days. The Morris water maze test was used to evaluate the ability of schisandrin to reduce phenobarbital-induced learning and memory impairment. The levels of superoxide dismutase (SOD) nitric oxide (NO) and catalase (CAT) were measured in brain tissue samples taken from the mice. Other biomarkers measured included expression of nuclear transcription factor-kappa-B (NF-κB) and brain-derived neurotrophic factor (BDNF) in the hippocampus CA1 region, which were determined by immunohistochemical analysis. On the fifth day of treatment, the mice in the pentobarbital sodium group performed worse on the Morris water maze test compared to untreated controls (P<0.01), which could be prolonged after schisandrin treatment (P<0.05 for="" low="" and="" intermediate="" dose="" groups="" analysis="" of="" brain="" tissues="" showed="" that="" compared="" with="" the="" control="" group="" no="" levels="" were="" increased="" sod="" cat="" activity="" decreased="" in="" pentobarbital="" sodium="" i="">P<0.01). After treatment with schisandrin, the NO levels were significantly decreased (P<0.01), while SOD and CAT activity increased (P<0.01). Immunohistochemistry analysis showed that, in phenobarbital only group, the protein expression of BDNF decreased, NF-κB increased compared to untreated controls, and schisandrin could reverse this trend (P<0.05 and="" i="">P<0.01, respectively). The results suggest that schisandrin is effective in improving the learning and memory deficiency induced by pentobarbital sodium, the mechanism of which may be related modulation of cellular response to oxidative stress.

scholarly journals Indoleamine 2,3-Dioxygenase-Dependent Neurotoxic Kynurenine Metabolism Contributes to Poststroke Depression Induced in Mice by Ischemic Stroke along with Spatial Restraint Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Young Soo Koo ◽  
Hyunha Kim ◽  
Jung Hwa Park ◽  
Min Jae Kim ◽  
Yong-Il Shin ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Nucleus Accumbens ◽  
Morris Water Maze ◽  
Water Maze ◽  
Restraint Stress ◽  
Sucrose Preference ◽  
Morris Water Maze Test ◽  
Maze Test ◽  
Ido1 Expression ◽  
Kynurenine Metabolism

Aim. Poststroke depression (PSD), which occurs in approximately one-third of stroke survivors, is clinically important because of its association with slow functional recovery and increased mortality. In addition, the underlying pathophysiological mechanisms are still poorly understood. Methods. We used a mouse model of PSD to examine the neurobiological mechanisms of PSD and the beneficial effects of aripiprazole, an atypical antipsychotic drug. PSD was induced in mice by combining middle cerebral artery occlusion (MCAO) with spatial restraint stress. The body weight, sucrose preference, and forced swim tests were performed at 5, 7, and 9 weeks and the Morris water maze test at 10 weeks after completing MCAO and spatial restraint stress. Results. Mice subjected to MCAO and spatial restraint stress showed significant depressive-like behavior in the sucrose preference test and forced swim test as well as cognitive impairment in the Morris water maze test. The PSD-like phenotype was accompanied by an indoleamine 2,3-dioxygenase 1 (IDO1) expression increase in the nucleus accumbens, hippocampus, and hypothalamus, but not in the striatum. Furthermore, the increased IDO1 levels were localized in Iba-1(+) cells but not in NeuN(+) or GFAP(+) cells, indicating that microglia-induced IDO1 expression was prominent in the PSD mouse brain. Moreover, 3-hydroxyanthranilate 3,4-dioxygenase (HAAO), quinolinic acid (QUIN), and reactive oxygen species (ROS) were significantly increased in the nucleus accumbens, hippocampus, and hypothalamus of PSD mice. Importantly, a 2-week aripiprazole (1 mg/kg, per os) regimen, which was initiated 1 day after MCAO, ameliorated depressive-like behavior and impairment of cognitive functions in PSD mice that was accompanied by downregulation of IDO1, HAAO, QUIN, and ROS. Conclusions. Our results suggest that the IDO1-dependent neurotoxic kynurenine metabolism induced by microglia functions in PSD pathogenesis. The beneficial effect of aripiprazole on depressive-like behavior and cognitive impairment may be mediated by inhibition of IDO1, HAAO, QUIN, and ROS.

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