Effects of Sodium Ferulate on Cognitive Function in Hippocampus of Chronic Cerebral Hypoperfusion Rats

2020 ◽  
Vol 10 (3) ◽  
pp. 329-335
Author(s):  
Yan Jiang ◽  
Hongyun Li ◽  
Chao Gong ◽  
Bin Fang ◽  
Xiaojing Huang
Keyword(s):  
Object Recognition ◽  
Cognitive Function ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Novel Object Recognition ◽  
Model Group ◽  
Sod Activity ◽  
Sodium Ferulate ◽  
Novel Object ◽  
P38mapk Signaling

Objective: To assess sodium ferulate’s effect on cognitive function and p38MAPK signaling in hippocampus of rats with chronic cerebral hypoperfusion (CCH). Methods: 45 male Sprague-Dawley (SD) rats were separated into sham-operation group, CCH model group and treatment group (intraperitoneal injection of 50 mg/kg sodium ferulate). The cognitive function was detected via open-field test, novel object recognition test and Morris water maze test. The activity of superoxide dismutase (SOD) in hippocampal tissues was detected using ELISA kit. Moreover, the neuronal damage in hippocampal tissues was assessed by immunohistochemical method, and apoptosis was assessed via TUNEL staining. Finally, p-p38MAPK signaling protein level in hippocampal tissues was detected via Western blotting. Results: No difference was found in rat autonomic activity among three groups (P > 0.05). The novel object recognition ability of model rats was significantly impaired along with longer escape latency and shorter retention time in the target quadrant (P < 0.01), which were all improved after sodium ferulate treatment (P < 0.01). SOD activity in hippocampal tissues in model rats was significantly reduced and sodium ferulate could significantly increase SOD activity (P < 0.01). There were a large number of damaged neurons and apoptotic cells in hippocampal tissues in model group and sodium ferulate could protect neurons (P < 0.01). The levels of p-p38MAPK, GSP3β and P-tau protein in hippocampal tissues in model group were significantly increased, which were significantly reduced after treatment with sodium ferulate (P < 0.01). Conclusion: Sodium ferulate can protect the CCH-induced cognitive impairment in rats and reduce the CCH-induced damage and apoptosis of hippocampal neurons, possibly through inhibition of p38MAPK signaling pathway.

scholarly journals Exercise Training Results in Lower Amyloid Plaque Load and Greater Cognitive Function in an Intensity Dependent Manner in the Tg2576 Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 10 (2) ◽  
pp. 88
Author(s):  
Riya Thomas ◽  
Scott D. Zimmerman ◽  
Kayla M. Yuede ◽  
John R. Cirrito ◽  
Leon M. Tai ◽  
...  
Keyword(s):  
Object Recognition ◽  
Cognitive Function ◽  
Exercise Training ◽  
Water Maze ◽  
Amyloid Plaque ◽  
Novel Object Recognition ◽  
Dependent Manner ◽  
Novel Object ◽  
Plaque Load ◽  
Tg2576 Mice

Three months of exercise training (ET) decreases soluble Aβ40 and Aβ42 levels in an intensity dependent manner early in life in Tg2576 mice (Moore et al., 2016). Here, we examined the effects of 12 months of low- and high- intensity exercise training on cognitive function and amyloid plaque load in the cortex and hippocampus of 15-month-old Tg2576 mice. Low- (LOW) and high- (HI) intensity ET animals ran at speeds of 15 m/min on a level treadmill and 32 m/min at a 10% grade, respectively, for 60 min/day, five days/week, from 3 to 15 months of age. Sedentary mice (SED) were placed on a level, non-moving, treadmill for the same duration. ET mice demonstrated a significantly lower amyloid plaque load in the cortex and hippocampus that was intensity dependent. Improvement in cognitive function, assessed by Morris Water Maze and Novel Object Recognition tests, was greater in the HI group compared to the LOW and SED groups. LOW mice performed better in the initial latency to the platform location during the probe trial of the Morris Water Maze (MWM) test than SED, but not in any other aspect of MWM or the Novel Object Recognition test. The results of this study indicate that exercise training decreases amyloid plaque load in an intensity dependent manner and that high-intensity exercise training improves cognitive function relative to SED mice, but the intensity of the LOW group was below the threshold to demonstrate robust improvement in cognitive function in Tg2576 mice.

scholarly journals Rosuvastatin Improves Cognitive Function of Chronic Hypertensive Rats by Attenuating White Matter Lesions and Beta-Amyloid Deposits

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Lu Zheng ◽  
Ying Cai ◽  
Baoshan Qiu ◽  
Linfang Lan ◽  
Jing Lin ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Object Recognition ◽  
Cognitive Function ◽  
White Matter ◽  
Water Maze ◽  
Novel Object Recognition ◽  
Hypertensive Rats ◽  
Object Recognition Test ◽  
Novel Object ◽  
Novel Object Recognition Test

Hypertensive white matter lesion (WML) is one of common causes of vascular cognitive impairment. In this study, we aimed to investigate the effect of rosuvastatin on cognitive impairment and its underlying mechanisms in chronic hypertensive rats. From the 8th week after establishment of stroke-prone renovascular hypertensive rats (RHRSPs), rosuvastatin (10 mg/kg) or saline as a control was administrated once daily for consecutive 12 weeks by gastric gavage. Cognitive function was assessed with the Morris water maze test and novel object recognition test. WML was observed by Luxol fast blue staining. Aβ deposits, Claudin-5, Occludin, and ZO-1 were determined by immunofluorescence. After rosuvastatin treatment, the escape latencies were decreased and the time of crossing the hidden platform was increased in the Morris water maze, compared with the vehicle-treated RHRSP group. In a novel object recognition test, the recognition index in the rosuvastatin-treated RHRSP group was significantly larger than that in the vehicle-treated RHRSP group. Rosuvastatin treatment presented with the effects of lower WML grades, higher expression of tight junction proteins Claudin-5, Occludin, and ZO-1 in the corpus callosum, and less Aβ deposits in the cortex and hippocampus. The data suggested that rosuvastatin improved the cognitive function of chronic hypertensive rats partly by attenuating WML and reducing Aβ burden.

scholarly journals Mice deficient in the NAAG synthetase II gene Rimkla are impaired in a novel object recognition task

2021 ◽  
Author(s):  
Ivonne Becker ◽  
Lihua Wang‐Eckhardt ◽  
Julia Lodder‐Gadaczek ◽  
Yong Wang ◽  
Agathe Grünewald ◽  
...  
Keyword(s):  
Object Recognition ◽  
Recognition Task ◽  
Novel Object Recognition ◽  
Novel Object ◽  
Object Recognition Task ◽  
Novel Object Recognition Task

A new rat model of chronic cerebral hypoperfusion associated with arteriovenous malformations

2002 ◽  
Vol 97 (5) ◽  
pp. 1198-1202 ◽  
Author(s):  
Jian Hai ◽  
Meixiu Ding ◽  
Zhilin Guo ◽  
Bingyu Wang
Keyword(s):  
Electron Microscopy ◽  
Animal Model ◽  
Arteriovenous Malformations ◽  
Perfusion Pressure ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Model Group ◽  
Content Type ◽  
The Right ◽  
Fine Print

Object. A new experimental model of chronic cerebral hypoperfusion was developed to study the effects of systemic arterial shunting and obstruction of the primary vessel that drains intracranial venous blood on cerebral perfusion pressure (CPP), as well as cerebral pathological changes during restoration of normal perfusion pressure. Methods. Twenty-four Sprague—Dawley rats were randomly assigned to either a sham-operated group, an arteriovenous fistula (AVF) group, or a model group (eight rats each). The animal model was readied by creating a fistula through an end-to-side anastomosis between the right distal external jugular vein (EJV) and the ispilateral common carotid artery (CCA), followed by ligation of the left vein draining the transverse sinus and bilateral external carotid arteries. Systemic mean arterial pressure (MAP), draining vein pressure (DVP), and CPP were monitored and compared among the three groups preoperatively, immediately postoperatively, and again 90 days later. Following occlusion of the fistula after a 90-day interval, blood—brain barrier (BBB) disruption and water content in the right cortical tissues of the middle cerebral artery territory were confirmed and also quantified with transmission electron microscopy. Formation of a fistula resulted in significant decreases in MAP and CPP, and a significant increase in DVP in the AVF and model groups. Ninety days later, there were still significant increases in DVP and decreases in CPP in the model group compared with the other groups (p < 0.05). Damage to the BBB and brain edema were noted in animals in the model group during restoration of normal perfusion pressure by occlusion of the fistula. Electron microscopy studies revealed cerebral vasogenic edema and/or hemorrhage in various amounts, which correlated with absent astrocytic foot processes surrounding some cerebral capillaries. Conclusions. The results demonstrated that an end-to-side anastomosis between the distal EJV and CCA can induce a decrease in CPP, whereas a further chronic state of cerebral hypoperfusion may be caused by venous outflow restriction, which is associated with perfusion pressure breakthrough. This animal model conforms to the basic hemodynamic characteristics of human cerebral arteriovenous malformations.

scholarly journals Social Factors Influence Behavior in the Novel Object Recognition Task in a Mouse Model of Down Syndrome

2021 ◽  
Vol 15 ◽  
Author(s):  
Cesar Sierra ◽  
Ilario De Toma ◽  
Lorenzo Lo Cascio ◽  
Esteban Vegas ◽  
Mara Dierssen
Keyword(s):  
Down Syndrome ◽  
Object Recognition ◽  
Environmental Factors ◽  
Mouse Models ◽  
Recognition Task ◽  
Novel Object Recognition ◽  
The Novel ◽  
Wild Type ◽  
Male And Female ◽  
Novel Object

The use of mouse models has revolutionized the field of Down syndrome (DS), increasing our knowledge about neuropathology and helping to propose new therapies for cognitive impairment. However, concerns about the reproducibility of results in mice and their translatability to humans have become a major issue, and controlling for moderators of behavior is essential. Social and environmental factors, the experience of the researcher, and the sex and strain of the animals can all have effects on behavior, and their impact on DS mouse models has not been explored. Here we analyzed the influence of a number of social and environmental factors, usually not taken into consideration, on the behavior of male and female wild-type and trisomic mice (the Ts65Dn model) in one of the most used tests for proving drug effects on memory, the novel object recognition (NOR) test. Using principal component analysis and correlation matrices, we show that the ratio of trisomic mice in the cage, the experience of the experimenter, and the timing of the test have a differential impact on male and female and on wild-type and trisomic behavior. We conclude that although the NOR test is quite robust and less susceptible to environmental influences than expected, to obtain useful results, the phenotype expression must be contrasted against the influences of social and environmental factors.

scholarly journals Cbsoverdosage is necessary and sufficient to induce cognitive phenotypes in mouse models of Down syndrome and interacts genetically withDyrk1a

2018 ◽  
Author(s):  
Damien Marechal ◽  
Véronique Brault ◽  
Alice Leon ◽  
Dehren Martin ◽  
Patricia Lopes Pereira ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Object Recognition ◽  
Synaptic Transmission ◽  
Actin Cytoskeleton ◽  
Epistatic Interaction ◽  
Novel Object Recognition ◽  
The Novel ◽  
Novel Object ◽  
Cystathionine Beta Synthase ◽  
Necessary And Sufficient

ABSTRACTIdentifying dosage sensitive genes is a key to understand the mechanisms underlying intellectual disability in Down syndrome (DS). The Dp(17Abcg1-Cbs)1Yah DS mouse model (Dp1Yah) show cognitive phenotype and needs to be investigated to identify the main genetic driver. Here, we report that, in the Dp1Yah mice, 3 copies of the Cystathionine-beta-synthase gene (Cbs)are necessary to observe a deficit in the novel object recognition (NOR) paradigm. Moreover, the overexpression ofCbsalone is sufficient to induce NOR deficit. Accordingly targeting the overexpression of human CBS, specifically in Camk2a-expressing neurons, leads to impaired objects discrimination. Altogether this shows thatCbsoverdosage is involved in DS learning and memory phenotypes. In order to go further, we identified compounds that interfere with the phenotypical consequence of CBS overdosage in yeast. Pharmacological intervention in the Tg(CBS) with one selected compound restored memory in the novel object recognition. In addition, using a genetic approach, we demonstrated an epistatic interaction betweenCbsandDyrk1a, another human chromosome 21 gene encoding the dual-specificity tyrosine phosphorylation-regulated kinase 1a and an already known target for DS therapeutic intervention. Further analysis using proteomic approaches highlighted several pathways, including synaptic transmission, cell projection morphogenesis, and actin cytoskeleton, that are affected by DYRK1A and CBS overexpression. Overall we demonstrated that CBS overdosage underpins the DS-related recognition memory deficit and that bothCBSandDYRK1Ainteract to control accurate memory processes in DS. In addition, our study establishes CBS as an intervention point for treating intellectual deficiencies linked to DS.SIGNIFICANT STATEMENTHere, we investigated a region homologous to Hsa21 and located on mouse chromosome 17. We demonstrated using three independent genetic approaches that the overdosage of the Cystathionine-beta-synthase gene (Cbs) gene, encoded in the segment, is necessary and sufficient to induce deficit in novel object recognition (NR).In addition, we identified compounds that interfere with the phenotypical consequence of CBS overdosage in yeast and in mouse transgenic lines. Then we analyzed the relation between Cbs overdosage and the consequence of DYRK1a overexpression, a main driver of another region homologous to Hsa21 and we demonstrated that an epistatic interaction exist betweenCbsandDyrk1aaffecting different pathways, including synaptic transmission, cell projection morphogenesis, and actin cytoskeleton.

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