SB-399885 is a potent, selective 5-HT6 receptor antagonist with cognitive enhancing properties in aged rat water maze and novel object recognition models

2006 ◽  
Vol 553 (1-3) ◽  
pp. 109-119 ◽  
Author(s):  
Warren D. Hirst ◽  
Tania O. Stean ◽  
Derek C. Rogers ◽  
David Sunter ◽  
Pippa Pugh ◽  
...  
2020 ◽  
Vol 178 (2) ◽  
pp. 347-357
Author(s):  
Muhammad M Hossain ◽  
Abdelmadjid Belkadi ◽  
Sara Al-Haddad ◽  
Jason R Richardson

Abstract Deficits in learning and memory are often associated with disruption of hippocampal neurogenesis, which is regulated by numerous processes, including precursor cell proliferation, survival, migration, and differentiation to mature neurons. Recent studies demonstrate that adult born neurons in the dentate gyrus (DG) in the hippocampus can functionally integrate into the existing neuronal circuitry and contribute to hippocampal-dependent learning and memory. Here, we demonstrate that relatively short-term deltamethrin exposure (3 mg/kg every 3 days for 1 month) inhibits adult hippocampal neurogenesis and causes deficits in learning and memory in mice. Hippocampal-dependent cognitive functions were evaluated using 2 independent hippocampal-dependent behavioral tests, the novel object recognition task and Morris water maze. We found that deltamethrin-treated mice exhibited profound deficits in novel object recognition and learning and memory in water maze. Deltamethrin exposure significantly decreased bromodeoxyuridine (BrdU)-positive cells (39%) and Ki67+ cells (47%) in the DG of the hippocampus, indicating decreased cellular proliferation. In addition, deltamethrin-treated mice exhibited a 44% decrease in nestin-expressing neural progenitor cells and a 38% reduction in the expression of doublecortin (DCX), an early neuronal differentiation marker. Furthermore, deltamethrin-exposed mice exhibited a 25% reduction in total number of granule cells in the DG. These findings indicate that relatively short-term exposure to deltamethrin causes significant deficits in hippocampal neurogenesis that is associated with impaired learning and memory.


2017 ◽  
Vol 04 (01) ◽  
pp. 036-045
Author(s):  
Gregory Smith ◽  
Nowrin Ahmed ◽  
Erin Arbuckle ◽  
Joaquin Lugo

Abstract Background One of the most devastating aspects of developmental epilepsy is the long-term impact on behavior. Children with epilepsy show a high co-morbidity with anxiety disorders and autism. Methods To examine whether early-life status epilepticus results in altered anxiety, repetitive behavior, social behavior, and learning and memory, we induced status epilepticus in male C57BL/6 mice on postnatal day (PD) 10. The mice received intraperitoneal injections of either kainic acid (2 mg/kg) or 0.9% normal saline. We also included a nontreated control group. Kainic acid induced status epilepticus for approximately 1.5 h. At PD60, the adult mice were then tested in a battery of behavioral tasks, including open field activity, elevated-plus maze, light-dark test, marble burying, social chamber, social partition, conditioned fear, novel object recognition, and Morris water maze. Results The early-life seizure group showed consistent increases in anxiety in the open field test (p < 0.05), elevated plus maze (p < 0.05), and light-dark task (p < 0.01). The seizure group showed significant (p < 0.01) impairment in the Morris water maze. There were no differences observed in marble burying, social partition, social chamber, novel object recognition, or delay fear conditioning tasks. Conclusions These results demonstrate that a single insult of status epilepticus during the neonatal period is sufficient to cause specific, long-term impairments in anxiety and spatial learning.


2020 ◽  
Vol 10 (2) ◽  
pp. 88
Author(s):  
Riya Thomas ◽  
Scott D. Zimmerman ◽  
Kayla M. Yuede ◽  
John R. Cirrito ◽  
Leon M. Tai ◽  
...  

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.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Lu Zheng ◽  
Ying Cai ◽  
Baoshan Qiu ◽  
Linfang Lan ◽  
Jing Lin ◽  
...  

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.


2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Ying-Chen Yang ◽  
Chia-Nan Chen ◽  
Carol-Imei Wu ◽  
Wei-Jan Huang ◽  
Tsun-Yung Kuo ◽  
...  

NBM-T-L-BMX-OS01 (BMX) was derived from the semisynthesis of osthole, isolated fromCnidium monnieri(L.) Cuss., and was identified to be a potent inhibitor of HDAC8. This study shows that HDAC8 is highly expressed in the pancreas and the brain. The function of HDAC8 in the brain has not been adequately studied. Because BMX enhances neurite outgrowth and cAMP response element-binding protein (CREB) activation, the effect of BMX on neural plasticity such as learning and memory is examined. To examine declarative and nondeclarative memory, a water maze, a passive one-way avoidance task, and a novel object recognition task were performed. Results from the water maze revealed that BMX and suberoylanilide-hydroxamic-acid-(SAHA-) treated rats showed shorter escape latency in finding the hidden platform. The BMX-treated animals spent more time in the target quadrant in the probe trial performance. An analysis of the passive one-way avoidance results showed that the BMX-treated animals stayed longer in the illuminated chamber by 1 day and 7 days after footshock. The novel object recognition task revealed that the BMX-treated animals showed a marked increase in the time spent exploring novel objects. Furthermore, BMX ameliorates scopolamine-(Sco-) induced learning and memory impairment in animals, indicating a novel role of BMX in learning and memory.


2021 ◽  
Vol 13 (2) ◽  
pp. 36-46
Author(s):  
A. T. Idris ◽  
A.M. Sunday ◽  
A.I. Ibrahim ◽  
O.N. James ◽  
A.K. Musa ◽  
...  

The study aimed to evaluate the effects of oral ingestion of hyoscyamine fraction of Daturastramonium seeds on the hippocampus in adult Wistar rats. Fresh seeds of D. stramonium were procured and fractionated using high-performance liquid chromatography (HPLC). Twenty-four healthy adult Wistar rats weighed 230±0.50 grams, were procured and divided equally into four groups for the experiment. The group one received an equivalent bodyweight of normal saline, while three other groups received 200, 400 and 800 mg/kgbwt of hyoscyamine fraction of D. stramonium respectively for three weeks. At the end of the experiment, the animals were subjected to memory test using Morris water maze (MWM) and Novel object recognition test (NORT) test paradigms. The data obtained were expressed as mean ± SEM and repeated measures ANOVA with Fisher’s multiple comparisons post-hoc tests were used to obtain mean differences using Minitab 17 (LLC., U.K.) statistical package software. P < 0.05  was considered statistically significant. There was a statistically significant increase in the exploration time (p = 0.031) and escape latency period (p < 0.001) in the novel object recognition and Morris water maze test between the groups in the treated compared to the control group. The CA3 region of the treated group showed significant neuronal lesions, cytoplasmic vacuolations, pyknosis and necrosis. . In conclusion, exposure to hyoscyamine fraction of D.stramonium at adulthood impaired memory in Wistar rats.  


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