scholarly journals Hippocampal Knockout of p300 Affects Learning and Memory in Mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 1044-1044
Author(s):  
Chase Rector ◽  
Lin Wang

Abstract Aging has been associated with cognitive decline, as seen in various learning and memory processes. Specifically, p300, a lysine acetyltransferase, has been shown to decrease with age, which could have an effect on cognition. In a series of behavioral tests, the effect of the knockout of p300 was studied in mice. In the water T maze test and the object recognition test, the results conveyed that the mice’s learning skills had not been impacted by the knockout of p300. But the water T maze test results further showed that the p300 knockout mice had a decline in their cognitive flexibility to new information. These findings suggest that the knockout of p300 has a negative impact on cognition. We expect that the overexpression of p300 in older mice will restore the cognition that might have been lost with aging.

2020 ◽  
Author(s):  
Fei Huang ◽  
Weixuan Xue ◽  
Yunyi Lan ◽  
Yanlin Tao ◽  
Jin Zhou ◽  
...  

Abstract Background: Astragaloside IV (ASIV) is one of the saponins isolated from Astragalus membranaceus, a widely used traditional Chinese medicine and a health product sold all over the world. However, so far, the effect of ASIV on GABAergic synaptic transmission has not been elucidated yet. In the present study, the effect of ASIV on memory and hippocampal GABAergic synaptic transmission was investigated in wild type and early growth response protein 1 (EGR-1) knockout mice. Methods: Behavioral tests including radial-arm maze test and shuttle-box test, liquid chromatography-tandem mass spectrometry, western blotting analysis, quantitative PCR, electrophysiological recording, and electron microscopy were used in this study. Results: ASIV was shown to enhance the learning and memory of mice in behavioral tests, such as radial-arm maze test and shuttle-box test. It significantly reduced the concentration of GABA, the expression of glutamate decarboxylase 2 (GAD65) as well as the ratio of inhibitory synapses in mouse hippocampus, which was accompanied with a suppression of hippocampal spontaneous inhibitory postsynaptic currents. ASIV administration decreased the expression of EGR-1, brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) in the hippocampus. Furthermore, blockage of BDNF/TrkB signaling with K-252a abrogated the effect of ASIV on GAD65 expression. When EGR-1 was knocked out, the promotive effects of ASIV on learning and memory, as well as the inhibitory effects on GABAergic synaptic transmission and GAD65, BDNF and TrkB expression, were abolished. In addition, ASIV was found to down-regulate the pre-existing EGR-1 baseline to better adapt to the learning stimuli. Conclusions: Together, these results demonstrated a novel role of ASIV in enhancing memory and reducing hippocampal GABAergic synaptic transmission through EGR-1 mediated BDNF/TrkB signaling pathway in mice.


2021 ◽  
Vol 12 ◽  
Author(s):  
Muxuan Han ◽  
Hao Zhang ◽  
Minghui Hu ◽  
Wei Sun ◽  
Zifa Li ◽  
...  

Background: Agarwood, a type of herbal medicine widely used in Asian countries, is noted in traditional medicine for its intelligence-enhancing effects. Agarwood incense is traditionally administered by oral and nasal inhalation. To verify whether agarwood incense can exert its intelligence-enhancing effects in this way to rescue learning and memory impairment, typical clinical manifestations of dementia, we conducted a set of behavioral tests related to learning and memory.Methods: C57BL/6 mice were divided into six groups. In addition to the control and model groups, we added a donepezil treatment group to evaluate the effect of three different agarwood administration doses. After a week of administration, scopolamine was injected 30 min before each behavioral test to create a learning and memory impairment model. A series of behavioral tests [the Morris water maze test (MWM), the novel object recognition test (NOR), and the step-down test (SDT)] were used to assess their learning ability, as well as their spatial and recognition memory.Results: After scopolamine injection, the model group showed significant learning and memory impairment (i.e., longer latencies, lower crossing times, and lesser distance travelled in the target quadrant in MWM; a lower recognition index in NOR; and longer latencies and higher error times in SDT). The other four treatment groups all showed improvements in these indicators, and the overall therapeutic effect of agarwood was superior.Conclusion: The inhalation administration of agarwood can significantly improve the learning and memory impairment caused by scopolamine in mice, and the therapeutic effect varied between doses.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3442
Author(s):  
Yaowared Chulikhit ◽  
Wichitsak Sukhano ◽  
Supawadee Daodee ◽  
Waraporn Putalun ◽  
Rakvajee Wongpradit ◽  
...  

The effects of the phytoestrogen-enriched plant Pueraria mirifica (PM) extract on ovari-ectomy (OVX)-induced cognitive impairment and hippocampal oxidative stress in mice were investigated. Daily treatment with PM and 17β-estradiol (E2) significantly elevated cognitive behavior as evaluated by using the Y maze test, the novel object recognition test (NORT), and the Morris water maze test (MWM), attenuated atrophic changes in the uterus and decreased serum 17β-estradiol levels. The treatments significantly ameliorated ovariectomy-induced oxidative stress in the hippocampus and serum by a decrease in malondialdehyde (MDA), an enhancement of superoxide dismutase, and catalase activity, including significantly down-regulated expression of IL-1β, IL-6 and TNF-α proinflammatory cytokines, while up-regulating expression of PI3K. The present results suggest that PM extract suppresses oxidative brain damage and dysfunctions in the hippocampal antioxidant system, including the neuroinflammatory system in OVX animals, thereby preventing OVX-induced cognitive impairment. The present results indicate that PM exerts beneficial effects on cognitive deficits for which menopause/ovariectomy have been implicated as risk factors.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hirotaka Shoji ◽  
Tsuyoshi Miyakawa

AbstractThe elevated plus maze test is a widely used test for assessing anxiety-like behavior and screening novel therapeutic agents in rodents. Previous studies have shown that a variety of internal factors and procedural variables can influence elevated plus maze behavior. Although some studies have suggested a link between behavior and plasma corticosterone levels, the relationships between them remain unclear. In this study, we investigated the effects of experience with a battery of behavioral tests, the wall color of the closed arms, and illumination level on the behavior and plasma corticosterone responses in the elevated plus maze in male C57BL/6J mice. Mice were either subjected to a series of behavioral tests, including assessments of general health and neurological function, a light/dark transition test, and an open field test, or left undisturbed until the start of the elevated plus maze test. The mice with and without test battery experience were allowed to freely explore the elevated plus maze. The other two independent groups of naïve mice were tested in mazes with closed arms with different wall colors (clear, transparent blue, white, and black) or different illumination levels (5, 100, and 800 lx). Immediately after the test, blood was collected to measure plasma corticosterone concentrations. Mice with test battery experience showed a lower percentage of open arm time and entries and, somewhat paradoxically, had lower plasma corticosterone levels than the mice with no test battery experience. Mice tested in the maze with closed arms with clear walls exhibited higher open arm exploration than mice tested in the maze with closed arms with black walls, while there were no significant differences in plasma corticosterone levels between the different wall color conditions. Illumination levels had no significant effects on any measure. Our results indicate that experience with other behavioral tests and different physical features of the maze affect elevated plus maze behaviors. Increased open arm time and entries are conventionally interpreted as decreased anxiety-like behavior, while other possible interpretations are considered: open arm exploration may reflect heightened anxiety and panic-like reaction to a novel situation under certain conditions. With the possibility of different interpretations, the present findings highlight the need to carefully consider the test conditions in designing experiments and drawing conclusions from the behavioral outcomes in the elevated plus maze test in C57BL/6J mice.


2020 ◽  
pp. 1-12
Author(s):  
Mareike Eschweiler ◽  
Lara Bohr ◽  
Josef Kessler ◽  
Gereon R. Fink ◽  
Elke Kalbe ◽  
...  

BACKGROUND: The negative impact of cognitive dysfunction on motor rehabilitation as a relearning-process is well known in stroke patients. However, evidence for combined cognitive and motor training (CMT) is lacking. OBJECTIVE: To evaluate the effects of combined CMT in early stroke rehabilitation. METHODS: In a controlled pilot study, 29 moderately affected stroke patients with low-level motor performance and cognitive impairment received motor therapy plus either cognitive (experimental group, EG) or low-frequency ergometer training (control group, CG) for eight days. RESULTS: Both groups improved their motor functioning significantly. After training, between-group comparison revealed significant differences for cognitive flexibility and trends for set-shifting, working memory, and reaction control in favor of the EG. Within-group effects showed improvement across all cognitive domains in the EG, which correlated with gains in bed-mobility, while the CG showed no significant improvement in cognition. Rather, a trend towards reaction control decline was observed, which correlated with less functional progression and recovery. Furthermore, a decline in cognitive flexibility, set-shifting, and working memory was descriptively observed. CONCLUSIONS: Combined CMT may enhance cognition and motor relearning early after stroke and is superior to single motor training. Further studies are needed to replicate these results and investigate long-term benefits.


2021 ◽  
Vol 19 ◽  
Author(s):  
Tingting Pi ◽  
Guangping Lang ◽  
Bo Liu ◽  
Jingshan Shi

Background: High methionine-diet (HMD) causes Alzheimer's disease (AD)-like symptoms. Previous studies have shown that Dendrobium nobile Lindle. alkaloids (DNLA) had potential benefits for AD. Object: Whether DNLA can improve AD-like symptoms induced by HMD is to be explored. Method: Mice were fed with 2% HMD diet for 11 weeks, the DNLA20 control group (20 mg/kg), DNLA10 group (10 mg/kg), and DNLA20 group (20 mg/kg) were administrated with DNLA for 3 months. Morris water maze test was used to detect learning and memory ability. Neuron damage was evaluated by HE and Nissl stainings. Levels of homocysteine (Hcy), beta-amyloid 1-42 (Aβ1-42), S-adenosine methionine (SAM), and S-adenosine homocysteine (SAH) were detected by ELISA. Immunofluorescence and western blotting (WB) were used to determine the expression of proteins. CPG island methylation. Results: Morris water maze test revealed that DNLA improved learning and memory dysfunction. HE, Nissl, and immunofluorescence stainings showed that DNLA alleviated neuron damage and reduced the 5-methylcytosine (5-mC), Aβ1-40, and Aβ1-42 levels. DNLA also decreased the levels of Hcy and Aβ1-42 in the serum, along with decreased SAM/SAH levels in the liver tissue. WB results showed that DNLA down-regulated the expression of the amyloid-precursor protein (APP), presenilin-1 (PS1), beta-secretase-1 (BACE1), DNA methyltransferase1 (DNMT1), Aβ1-40, and Aβ1-42 proteins. DNLA also up-regulated the expression of the protein of insulin-degrading enzyme (IDE), neprilysin (NEP), DNMT3a, and DNMT3b. Meanwhile, DNLA increased CPG island methylation levels of APP and BACE1 genes. Conclusions: DNLA alleviated AD-like symptoms induced by HMD via the DNA methylation pathway.


2019 ◽  
Vol 8 (2) ◽  
pp. 69
Author(s):  
Muhaiminah Akib ◽  
Dian Saputra

The purpose of this study was to investigate the effect of the dictogloss method in teaching listening to students' listening skills. This research was designed as a quasi-experimental. This study aims to investigate whether a material or treatment yields a different outcome for participants. There are two classes in this study, namely the experimental class (which is a sample to be treated with the dictogloss method) and the control class (using a method other than dictogloss). The results of this study are the results of data analysis showing that the results of learning skills in listening to the experimental group obtained the average value for the initial test of 60.33 and 71 for the final test score. While the control group using conventional methods has a mean value for the initial test of 60.1 and 70 for the final test. T test results also indicate that the significance value is 0,000. The significance value states smaller 0.05, it can be stated that Ha is accepted and Ho is rejected, which means that there is an influence of the dictogloss method in improving listening skills in students


2013 ◽  
Vol 411-414 ◽  
pp. 3178-3180
Author(s):  
Li Hai Jin ◽  
Xing Yu Zhao ◽  
Wei Zhang ◽  
Wei Chen ◽  
Guo Qing Sun ◽  
...  

We assessed the effectiveness and mechanism of action of Soybean Isoflavones on learning and memory and Caspase-3 levels in the hippocampus of rats after Morris water maze (MWM test). Soybean Isoflavones (200,400 or 800 mg/kg/d) were administered by intragavage once daily for 14 consecutive days. The Morris water maze test was used to evaluate the ability of Soybean Isoflavones to increase learning and memory impairment. The levels of Caspase-3 in hippocampus of rats were detected by Westernblot after MWM test. Compared to untreated controls (P<0.01), MWM could be prolonged after Soybean Isoflavones treatment (P<0.05 for="" low="" and="" intermediate="" dose="" groups="" westernblot="" analysis="" showed="" that="" the="" protein="" expression="" of="" caspase-3="" was="" decreased="" in="" different="" concentration="" soybean="" isoflavones="" i="">P<0.05 and="" i="">P<0.01, respectively). The results suggest that Soybean Isoflavones is effective in improving the learning and memory in rats , the mechanism of which may be related Caspase ways.


Author(s):  
J. Park ◽  
Y. Kim ◽  
M. Woo

Aims: This study examined the interactive effect of physical fitness and Apolipoprotein e4 on intelligence and cortical networking in adolescents. Methods: Participants were middle school students consisting of 10 and 8 high- and low-fit e4 carriers (e4+), respectively, and 14 and 10 high- and low-fit non-carriers (e4−), respectively. Inter- and intra-hemispheric coherences were calculated to examine cortico-cortical communication during intelligence test. Results: Coherence in low-fit e4+ was lower than in high-fit e4+, while coherence in low-fit e4- was similar to or higher than in high-fit e4-. Conclusion: the presence of the e4 allele can decrease neural networking 50-60 years before Alzheimer’s disease onset: however, physical fitness may compensate for the negative impact of genotype. Moreover, the beneficial effects of physical fitness may differ depending on functional states of the adolescent brain according to the presence of the e4 allele.


Sign in / Sign up

Export Citation Format

Share Document