scholarly journals Oestrogen receptor α agonist improved long-term ovariectomy-induced spatial cognition deficit in young rats

2013 ◽  
Vol 16 (5) ◽  
pp. 1071-1082 ◽  
Author(s):  
Na Qu ◽  
Lei Wang ◽  
Zan-Chao Liu ◽  
Qing Tian ◽  
Qi Zhang
Keyword(s):  
Cognitive Impairment ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Oestrogen Receptor ◽  
Synaptic Proteins ◽  
Ovariectomized Rats ◽  
Spatial Learning And Memory ◽  
Apoptosis Protein ◽  
Oestrogen Receptor Α

Abstract Ovariectomy is known as ‘surgical menopause’ with decreased levels of oestrogen in female rodents and its reported risks and adverse effects include cognitive impairment. In the brain, oestrogen exerts effects through its receptors, oestrogen receptor α (ERα) and β (ERβ). However, the role of ERα or ERβ in ovariectomy-induced cognitive impairment needs further investigation. Here, we observed that bilaterally ovariectomized 3-month-old rats showed obvious spatial learning and memory deficits in the Morris water maze with significant loss of neurons and synapses in the hippocampus. In addition to the rapid decline in serum oestradiol levels, the expression of ERα, but not ERβ, was decreased in the hippocampus starting 1 wk after ovariectomy. Prompt 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT) treatment (1 mg/kg.d), an agonist of ERα, improved the spatial learning and memory ability of ovariectomized rats and rescued ovariectomy-induced neuron loss by up-regulating the level of BCLxl, an important anti-apoptosis protein. Furthermore, PPT treatment also improved ovariectomy-induced hippocampal synapse loss and up-regulated the levels of synaptic proteins (synapsin I, NR2A and GluR1) and the activates of CaMK Πα, ERK and Akt. Thus, these results demonstrated that ERα plays an important role in neuroprotection and that prompt ERα rescue is effective to improve hippocampal-dependent cognition deficit after long-term ovariectomy.

scholarly journals Tripchlorolide May Improve Spatial Cognition Dysfunction and Synaptic Plasticity after Chronic Cerebral Hypoperfusion

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Zhao-Hui Yao ◽  
Xiao-li Yao ◽  
Shao-feng Zhang ◽  
Ji-chang Hu ◽  
Yong Zhang
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Long Term Potentiation ◽  
Chronic Cerebral Hypoperfusion ◽  
Synaptic Proteins ◽  
Cerebral Hypoperfusion ◽  
Spatial Learning And Memory ◽  
Pathophysiological Mechanism

Chronic cerebral hypoperfusion (CCH) is a common pathophysiological mechanism that underlies cognitive decline and degenerative processes in dementia and other neurodegenerative diseases. Low cerebral blood flow (CBF) during CCH leads to disturbances in the homeostasis of hemodynamics and energy metabolism, which in turn results in oxidative stress, astroglia overactivation, and synaptic protein downregulation. These events contribute to synaptic plasticity and cognitive dysfunction after CCH. Tripchlorolide (TRC) is an herbal compound with potent neuroprotective effects. The potential of TRC to improve CCH-induced cognitive impairment has not yet been determined. In the current study, we employed behavioral techniques, electrophysiology, Western blotting, immunofluorescence, and Golgi staining to investigate the effect of TRC on spatial learning and memory impairment and on synaptic plasticity changes in rats after CCH. Our findings showed that TRC could rescue CCH-induced spatial learning and memory dysfunction and improve long-term potentiation (LTP) disorders. We also found that TRC could prevent CCH-induced reductions in N-methyl-D-aspartic acid receptor 2B, synapsin I, and postsynaptic density protein 95 levels. Moreover, TRC upregulated cAMP-response element binding protein, which is an important transcription factor for synaptic proteins. TRC also prevented the reduction in dendritic spine density that is caused by CCH. However, sham rats treated with TRC did not show any improvement in cognition. Because CCH causes disturbances in brain energy homeostasis, TRC therapy may resolve this instability by correcting a variety of cognitive-related signaling pathways. However, for the normal brain, TRC treatment led to neither disturbance nor improvement in neural plasticity. Additionally, this treatment neither impaired nor further improved cognition. In conclusion, we found that TRC can improve spatial learning and memory, enhance synaptic plasticity, upregulate the expression of some synaptic proteins, and increase the density of dendritic spines. Our findings suggest that TRC may be beneficial in the treatment of cognitive impairment induced by CCH.

scholarly journals Effects of Gestational Inflammation with Postpartum Enriched Environment on Age-Related Changes in Cognition and Hippocampal Synaptic Plasticity-Related Proteins

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Shi-Yu Sun ◽  
Xue-Yan Li ◽  
He-Hua Ge ◽  
Yu-Xin Zhang ◽  
Zhe-Zhe Zhang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Enriched Environment ◽  
Synaptic Proteins ◽  
Spatial Learning And Memory ◽  
Age Related ◽  
Related Proteins ◽  
Age Related Changes

Increasing evidence indicates that exposure to inflammation during pregnancy intensifies the offspring’s cognitive impairment during aging, which might be correlated with changes in some synaptic plasticity-related proteins. In addition, an enriched environment (EE) can significantly exert a beneficial impact on cognition and synaptic plasticity. However, it is unclear whether gestational inflammation combined with postnatal EE affects the changes in cognition and synaptic plasticity-related proteins during aging. In this study, pregnant mice were intraperitoneally injected with lipopolysaccharides (LPS, 50 μg/kg) or normal saline at days 15–17 of pregnancy. At 21 days after delivery, some LPS-treated mice were randomly selected for EE treatment. At the age of 6 and 18 months, Morris water maze (MWM) and western blotting were, respectively, used to evaluate or measure the ability of spatial learning and memory and the levels of postsynaptic plasticity-related proteins in the hippocampus, including postsynaptic density protein 95 (PSD-95), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluA1 subunit, and Homer-1b/c. The results showed that 18-month-old control mice had worse spatial learning and memory and lower levels of these synaptic plasticity-related proteins (PSD-95, GluA1, and Homer-1b/c) than the 6-month-old controls. Gestational LPS exposure exacerbated these age-related changes of cognition and synaptic proteins, but EE could alleviate the treatment effect of LPS. In addition, the performance during learning and memory periods in the MWM correlated with the hippocampal levels of PSD-95, GluA1, and Homer-1b/c. Our results suggested that gestational inflammation accelerated age-related cognitive impairment and the decline of PSD-95, GluA1, and Homer-1b/c protein expression, and postpartum EE could alleviate these changes.

scholarly journals A Long-Term Enriched Environment Ameliorates the Accelerated Age-Related Memory Impairment Induced by Gestational Administration of Lipopolysaccharide: Role of Plastic Mitochondrial Quality Control

2021 ◽  
Vol 14 ◽  
Author(s):  
Zhan-Qiang Zhuang ◽  
Zhe-Zhe Zhang ◽  
Yue-Ming Zhang ◽  
He-Hua Ge ◽  
Shi-Yu Sun ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Memory Impairment ◽  
Spatial Learning And Memory ◽  
Mitochondrial Quality Control ◽  
Protein Levels ◽  
Age Related ◽  
Old Mice ◽  
Lps Treatment

Studies have shown that gestational inflammation accelerates age-related memory impairment in mother mice. An enriched environment (EE) can improve age-related memory impairment, whereas mitochondrial dysfunction has been implicated in the pathogenesis of brain aging. However, it is unclear whether an EE can counteract the accelerated age-related memory impairment induced by gestational inflammation and whether this process is associated with the disruption of mitochondrial quality control (MQC) processes. In this study, CD-1 mice received daily intraperitoneal injections of lipopolysaccharide (LPS, 50 μg/kg) or normal saline (CON group) during gestational days 15–17 and were separated from their offspring at the end of normal lactation. The mothers that received LPS were divided into LPS group and LPS plus EE (LPS-E) treatment groups based on whether the mice were exposed to an EE until the end of the experiment. At 6 and 18 months of age, the Morris water maze test was used to evaluate spatial learning and memory abilities. Quantitative reverse transcription polymerase chain reaction and Western blot were used to measure the messenber RNA (mRNA) and protein levels of MQC-related genes in the hippocampus, respectively. The results showed that all the aged (18 months old) mice underwent a striking decline in spatial learning and memory performances and decreased mRNA/protein levels related to mitochondrial dynamics (Mfn1/Mfn2, OPA1, and Drp1), biogenesis (PGC-1α), and mitophagy (PINK1/parkin) in the hippocampi compared with the young (6 months old) mice. LPS treatment exacerbated the decline in age-related spatial learning and memory and enhanced the reduction in the mRNA and protein levels of MQC-related genes but increased the levels of PGC-1α in young mice. Exposure to an EE could alleviate the accelerated decline in age-related spatial learning and memory abilities and the accelerated changes in MQC-related mRNA or protein levels resulting from LPS treatment, especially in aged mice. In conclusion, long-term exposure to an EE can counteract the accelerated age-related spatial cognition impairment modulated by MQC in CD-1 mother mice that experience inflammation during pregnancy.

scholarly journals Effects of Chronic Administration of Pioglitazone on Learning and Memory in Rat Model of Streptozotocin-induced Alzheimer’s Disease

2020 ◽  
Vol 24 (4) ◽  
pp. 294-307
Author(s):  
Ehsan Aali ◽  
◽  
Mohammad Hossein Esmaeili ◽  
Sead Shima Mahmodi ◽  
Poriea Solimani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Rat Model ◽  
Escape Latency ◽  
Chronic Administration ◽  
Spatial Learning And Memory ◽  
Swimming Time

Background: Alzheimer’s Disease (AD) is a chronic neurodegenerative disease characterized by abnormal protein accumulation, synaptic dysfunction, and cognitive impairment. Peroxisome Proliferator-Activated Receptor-γ (PPARγ) play a crucial role in regulating insulin sensitivity and may serve as potential therapeutic targets for AD. Pioglitazone (PIOG), as a PPARγ agonist, reduces β-amyloid and tau proteins, and inhibits neuroinflammation. Objective: This study aims to evaluate the effects of PIOG chronic administration on learning and memory in rat model of Streptozotocin (STZ)-induced AD Methods: Forty-two male Wistar rats were divided into two groups: A. Normal rats divided into three subgroups of Control, Dimethyl Sulfoxide (DMSO), and PIOG; and B. AD rats divided into four subgroups of Vehicle, STZ, STZ+DMSO and STZ+PIOG. The last two AD subgroups received 0.2 mL DMSO and PIOG (10 mg/kg per day) for 21 days. For induction of AD, STZ (3 mg/kg, 10 μl per injection site) were administered into lateral ventricles. All rates were trained under the Morris water maze task. Findings: PIOG impaired the spatial learning and memory in normal rats. Intracerebroventricular injection of STZ significantly increased escape latency and swimming time to find the hidden platform compared to the control group (P<0.05). The amnesic effect of STZ was prevented by PIOG administration such that the escape latency and swimming time to find the hidden platform in the STZ+PIOG group were significantly lower than in the STZ+DMSO group (P<0.05). Conversely, the percentage of time spent and distance swimming in the target quadrant in the probe test in the STZ+ PIOG group rats were significantly higher than those in the STZ + DMSO group. Conclusion: PIOG administration impaired spatial learning and memory in normal rats, but improved learning and memory in rats with STZ-induced AD. It can be useful for treatment of cognitive impairment in AD patients.

The effects of soy on scopolamine-induced spatial learning and memory impairments are comparable to the effects of estradiol

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Narges Marefati ◽  
Amin Mokhtari-Zaer ◽  
Farimah Beheshti ◽  
Sareh Karimi ◽  
Zahra Mahdian ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Serum Levels ◽  
Ovariectomized Rats ◽  
Control Group ◽  
Spatial Learning And Memory ◽  
Protective Effects ◽  
Memory Impairments ◽  
The Central Nervous System ◽  
Higher Doses

Abstract Background Modulatory effects of soy extract and estradiol on the central nervous system (CNS) have been reported. The effect of soy on scopolamine-induced spatial learning and memory in comparison to the effect of estradiol was investigated. Materials and methods Ovariectomized rats were divided into the following groups: (1) control, (2) scopolamine (Sco), (3) scopolamine-soy 20 (Sco-S 20), (4) scopolamine-soy 60 (Sco-S 60), (5) scopolamine-estradiol 20 (Sco-E 20) and (6) scopolamine-estradiol 60 (Sco-E 60). Soy extract, estradiol and vehicle were administered daily for 6 weeks before training in the Morris water maze (MWM) test. Scopolamine (2 mg/kg) was injected 30 min before training in the MWM test. Results In the MWM, the escape latency and traveled path to find the platform in the Sco group was prolonged compared to the control group (p < 0.001). Treatment by higher doses of soy improved performances of the rats in the MWM (p < 0.05 – p < 0.001). However, treatment with both doses of estradiol (20 and 60 μg/kg) resulted in a statistically significant improvement in the MWM (p < 0.01 – p < 0.001). Cortical, hippocampal and serum levels of malondialdehyde (MDA), as an index of lipid peroxidation, were increased which was prevented by soy extract and estradiol (p < 0.001). Cortical, hippocampal as well as serum levels of the total thiol, superoxide dismutase (SOD) and catalase (CAT) in Sco group were lower than the control group (p < 0.001) while they were enhanced when the animals were treated by soy extract and estradiol (p < 0.01 – p < 0.001). Conclusions It was observed that both soy extract and estradiol prevented learning and memory impairments induced by scopolamine in ovariectomized rats. These effects can be attributed to their protective effects on oxidative damage of the brain tissue.

Post-weaning mice fed exclusively milk have deficits in induction of long-term depression in the CA1 hippocampal region and spatial learning and memory

2012 ◽  
Vol 73 (4) ◽  
pp. 292-301 ◽  
Author(s):  
Hideaki Nishie ◽  
Ryouhei Miyata ◽  
Ryu Fujikawa ◽  
Ken-ichi Kinoshita ◽  
Yoshikage Muroi ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Spatial Learning And Memory ◽  
Hippocampal Region ◽  
Long Term Depression

scholarly journals Effect of Short- and Long-Term Administration of Baclofen on Spatial Learning and Memory in Rats

2018 ◽  
pp. 133-141 ◽  
Author(s):  
M. HOLAJOVA ◽  
M. FRANEK
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Receptor Agonist ◽  
Gabab Receptor ◽  
Spatial Learning And Memory ◽  
Adult Rats ◽  
Treatment Groups ◽  
Term Administration ◽  
Short And Long Term

Baclofen is the only clinically available metabotropic GABAB receptor agonist. In our experiment, we tested the hypothesis that long-term baclofen administration can impair learning and memory in rats. The experiment consisted of three parts. In the first part of the study the drug was administered simultaneously with the beginning of the behavioral tests. In the second and third part of the experiment baclofen was administered daily for 14 days and for one month before the tests. In each part of the experiment, adult rats were randomly divided into four treatment groups. Three groups were given an injection of baclofen at doses of 1 mg/kg, 5 mg/kg, 10 mg/kg, while the fourth group was injected with saline. The injections were given after each session. Spatial learning and memory were tested using the Morris water maze, involving three types of tests: Acquisition, Probe, and Re-acquisition. This work reveals that baclofen did not affect spatial learning at any of the tested doses and regardless of the length of administration. Memory was observed to be affected, but only at the highest dose of baclofen and only temporarily. This conclusion is in line with previously published clinical cases.

scholarly journals The Contribution of Stem Cell Factor and Granulocyte Colony-Stimulating Factor in Reducing Neurodegeneration and Promoting Neural Network Reorganization after Traumatic Brain Injury

2020 ◽  
Author(s):  
Junchi He ◽  
Thomas Russell ◽  
Xuecheng Qiu ◽  
Fei Hao ◽  
Michele Kyle ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Spatial Learning And Memory ◽  
Granulocyte Colony Stimulating Factor ◽  
Hippocampal Ca1 ◽  
Severe Tbi ◽  
Apical Dendrites ◽  
Stimulating Factor

Abstract Background Traumatic brain injury (TBI) is a major cause of death and disability in young adults worldwide. TBI-induced long-term cognitive deficits represent a growing clinical problem. Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are involved in neuroprotection and neuronal plasticity. However, the knowledge concerning reparative efficacy of SCF+G-CSF treatment in post-acute TBI recovery remains incomplete. This study aims to determine the efficacy of SCF+G-CSF on post-acute TBI recovery in young adult mice. The controlled cortical impact model of TBI was used for inducing a severe damage in the motor cortex of the right hemisphere in 8-week-old male C57BL mice. SCF+G-CSF treatment was initiated 3 weeks after induction of TBI. Results Severe TBI led to persistent motor functional deficits (Rota-Rod test) and impaired spatial learning and memory (Morris water maze test). SCF+G-CSF treatment significantly improved the severe TBI-impaired spatial learning and memory 6 weeks after treatment. TBI also caused significant increases of Fluoro-Jade C positive degenerating neurons in bilateral frontal cortex, striatum and hippocampus, and significant reductions in MAP2 + apical dendrites and overgrowth of SMI312 + axons in peri-TBI cavity frontal cortex and in the ipsilateral hippocampal CA1 at 24 weeks post-TBI. SCF+G-CSF treatment significantly reduced TBI-induced neurodegeneration in the contralateral frontal cortex and hippocampal CA1, increased MAP2 + apical dendrites in the peri-TBI cavity frontal cortex, and prevented TBI-induced axonal overgrowth in both the peri-TBI cavity frontal cortex and ipsilateral hippocampal CA1. Conclusions These findings reveal a novel pathology of axonal overgrowth after TBI and demonstrate a therapeutic potential of SCF+G-CSF in ameliorating TBI-induced long-term neuronal pathology, neural network malformation, and impairments in spatial learning and memory.

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