scholarly journals Genetic Inactivation of Two-Pore Channel 1 Impairs Spatial Learning and Memory

2020 ◽  
Vol 50 (6) ◽  
pp. 401-410
Author(s):  
Robert Theodor Mallmann ◽  
Norbert Klugbauer
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Motor Performance ◽  
Motor Coordination ◽  
Morris Water Maze Test ◽  
Pore Channel ◽  
Spatial Learning And Memory ◽  
Genetic Inactivation ◽  
Maze Test ◽  
Higher Order Functions

Abstract Two-pore channels (TPCs) constitute a small family of cation channels that are localized in membranes of endosomal and lysosomal compartments. Although their roles for vesicular fusion and endolysosomal trafficking have been investigated, our knowledge on their expression pattern and higher order functions in the murine brain is still limited. Western blot analysis indicated a broad expression of TPC1 in the neocortex, cerebellum and hippocampus. In order to investigate the consequences of the genetic inactivation of TPC1, we performed a set of behavioural studies with TPC1−/− mice. TPC1−/− mice were analysed for an altered motor coordination and grip-strength, exploratory drive and anxiety as well as learning and memory. TPC1−/− mice did not show any differences in their exploratory drive or in their anxiety levels. There were also no differences in spontaneous activity or motor performance. However, the Morris water maze test uncovered a deficit in spatial learning and memory in TPC1−/− mice.

scholarly journals Angiostrongylus cantonensis causes cognitive impairments in heavily infected BALB/c and C57BL/6 mice

2020 ◽  
Author(s):  
Kai-Yuan Jhan ◽  
Guan-Jhih Lai ◽  
Pi-Kai Chang ◽  
Ren-Yu Tang ◽  
Chien-Ju Cheng ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Forced Swimming Test ◽  
Open Field Test ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
Dietary Consumption ◽  
Maze Test ◽  
Behavior Learning ◽  
Swimming Test

Abstract Background: Parasitic infections may cause significant effects on behavior, learning, and memory of the hosts. In the brain of mice heavily infected with Angiostrongylus cantonensis, severe damages have been observed in the hippocampus. This component has been considered to have associations with spatial learning and memory in human and vertebrates. This study was designed to determine the impairments in behavior, learning, and memory in BALB/c and C57BL/6 mice heavily infected with the parasite. Methods: Each mouse was inoculated with 50 third-stage larvae of A. cantonensis. After infection, daily changes in weight and dietary consumption, worm recoveries and survival rates were determined. The forced swimming test, open field test, and Morris water maze test were employed to evaluate depression- and anxiety-like behavior as well as impairments in spatial learning and memory, respectively. In addition, in the two strains of mice were also determined. Results: The worm recovery rate in the BALB/c mice was significantly lower than that of C57BL/6 mice since day 14 post-infection. The survival rate in infected BALB/c mice decreased to 0% by day 25 whereas those with swim-training survived three more days. On day 42, the C57BL/6 mice had a survival rate of 85.7% in the swimming group and 70% in the non-swimming group. Significant differences were found in weight between infected and non-infected BALB/c and C57BL/6 mice since day 13 and day 12, respectively with corresponding changes in the dietary consumption. Depression-like behavior was found in the infected BALB/c mice but not in C57BL/6 mice. However, anxiety-like behavior was found to occur only in C57BL/6 mice. Impaired spatial learning and memory were also found in the two strains of mice occurred since day 14 post-infection. Conclusions: Results of this study indicate that A. cantonensis causes depression, anxiety, and impairments in spatial learning and memory in heavily infected mice. Moreover, significantly higher severity was observed in the Th-2 dominant BALB/c mice. Keywords: Angiostrongyliasis cantonensis, mice, behavior, learning, memory, forced swimming test, open field test, Morris water maze test

Anti-HIV drugs promote β-amyloid deposition and impair learning and memory in BALB/c mice

2020 ◽  
Vol 32 (5) ◽  
pp. 257-264
Author(s):  
S.S. Zulu ◽  
O. Abboussi ◽  
N. Simola ◽  
M.V. Mabandla ◽  
W.M.U. Daniels
Keyword(s):  
Lipid Peroxidation ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Water Maze ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
Maze Test ◽  
Bace1 Expression ◽  
Hiv Drugs ◽  
Anti Hiv

AbstractObjectives:Growing evidence suggested that antiretroviral (ARV) drugs may promote amyloid beta (Aβ) accumulation in HIV-1-infected brain and the persistence of HIV-associated neurocognitive disorders (HANDs). It has also been shown that lipid peroxidation upregulates β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) expression and subsequently promotes Aβ peptide production. In the present study, we examined whether chronic exposure to the anti-HIV drugs tenofovir disoproxil fumarate (TDF) and nevirapine induces lipid peroxidation thereby promoting BACE1 and Aβ generation and consequently impair cognitive function in mice.Methods:TDF or nevirapine was orally administered to female BALB/c mice once a day for 8 weeks. On the 7th week of treatment, spatial learning and memory were assessed using the Morris water maze test. The levels of lipid peroxidation, BACE1, amyloid β 1-42 (Aβ1-42) and Aβ deposits were measured in the hippocampal tissue upon completion of treatment.Results:Chronic administration of nevirapine induced spatial learning and memory impairment in the Morris water maze test, whereas TDF did not have an effect. TDF and nevirapine administration increased hippocampal lipid peroxidation and Aβ1-42 concentration. Nevirapine further upregulated BACE1 expression and Aβ deposits.Conclusion:Our results suggest that chronic exposure to TDF and nevirapine contributes to hippocampal lipid peroxidation and Aβ accumulation, respectively, as well as spatial learning and memory deficits in mice even in the absence of HIV infection. These findings further support a possible link between ARV drug toxicity, Aβ accumulation and the persistence of HANDs.

scholarly journals GABAB receptor antagonist promotes hippocampal neurogenesis and facilitates cognitive function recovery following acute cerebral ischemia in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dan Song ◽  
Yaohua Chen ◽  
Cheng Chen ◽  
Lili Chen ◽  
Oumei Cheng
Keyword(s):  
Cognitive Function ◽  
Cerebral Ischemia ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurogenesis ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
In Vitro Experiments ◽  
Adult Mice

Abstract Purpose and background Previous studies have suggested that promoting endogenous neurogenesis has great significance for the recovery of cognitive dysfunction caused by cerebral ischemia (CI). Pharmacological inhibition of GABAB receptor can enhance neurogenesis in adult healthy and depressed mice. In the study, we intended to investigate the effects of GABAB receptor antagonists on cognitive function and hippocampal neurogenesis in mice following CI. Methods Adult mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 20 min to induce CI and treated with CGP52432 (antagonist of GABAB receptor, CGP, 10 mg/kg intraperitoneal injection) starting 24 h after CI. The Morris water maze test was performed to test spatial learning and memory at day 28. Immunofluorescence was applied to detect neurogenesis in the DG region at day 14 and 28. In in vitro experiments, cell proliferation was detected by CCK8 and immunofluorescence, and the expression of cAMP/CREB signaling pathway-related proteins was detected by ELISA assay and Western blot. Results CGP significantly improved spatial learning and memory disorders caused by CI, and it enhanced the proliferation of neural stem cells (NSCs), the number of immature neurons, and the differentiation from newborn cells to neurons. In vitro experiments further confirmed that CGP dose-dependently enhanced the cell viability of NSCs, and immunofluorescence staining showed that CGP promoted the proliferation of NSCs. In addition, treatment with CGP increased the expression of cAMP, PKA, and pCREB in cultured NSCs. Conclusion Inhibition of GABAB receptor can effectively promote hippocampal neurogenesis and improve spatial learning and memory in adult mice following CI.

scholarly journals Nrf2 Ablation Promotes Alzheimer’s Disease-Like Pathology in APP/PS1 Transgenic Mice: The Role of Neuroinflammation and Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Peng Ren ◽  
Jingwei Chen ◽  
Bingxuan Li ◽  
Mengzhou Zhang ◽  
Bei Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
Related Factor ◽  
Qrt Pcr

Introduction. Alzheimer’s disease (AD), the most common neurodegenerative disorder, is characterized by the accumulation of amyloid-β (Aβ) peptide and hyperphosphorylated tau protein. Accumulating evidence has revealed that the slow progressive deterioration of AD is associated with oxidative stress and chronic inflammation in the brain. Nuclear factor erythroid 2- (NF-E2-) related factor 2 (Nrf2), which acts through the Nrf2/ARE pathway, is a key regulator of the antioxidant and anti-inflammatory response. Although recent data show a link between Nrf2 and AD-related cognitive decline, the mechanism is still unknown. Thus, we explored how Nrf2 protects brain cells against the oxidative stress and inflammation of AD in a mouse model of AD (APP/PS1 transgenic (AT) mice) with genetic removal of Nrf2. Methods. The spatial learning and memory abilities of 12-month-old transgenic mice were evaluated using a Morris water maze test. Hippocampal levels of Nrf2, Aβ, and p-tauS404 and of astrocytes and microglia were determined by immunostaining. Inflammatory cytokines were determined by ELISA and quantitative real-time polymerase chain reaction (qRT-PCR). Oxidative stress was measured by 8-hydroxydeoxyguanosine immunohistochemistry, and the antioxidant response was determined by qRT-PCR. Results. The spatial learning and memory abilities of AT mice were impaired after Nrf2 deletion. Aβ and p-tauS404 accumulation was increased in the hippocampus of AT/Nrf2-KO mice. Astroglial and microglial activation was exacerbated, followed by upregulation of the proinflammatory cytokines IL-1β, IL-6, and TNF-α. Conclusion. Our present results show that Nrf2 deficiency aggravates AD-like pathology in AT mice. This phenotype was associated with increased levels of oxidative and proinflammatory markers, which suggests that the Nrf2 pathway may be a promising therapeutic target for AD.

scholarly journals The Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Prone 8 Mice

2020 ◽  
Author(s):  
Kazunori Sasaki ◽  
Noelia Geribaldi-Doldan ◽  
Qingqing Wu ◽  
Julie Davies ◽  
Francis G. Szele ◽  
...  
Keyword(s):  
Stem Cells ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Neural Development ◽  
Learning Ability ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
Age Related ◽  
And Function ◽  
Samp8 Mice

Abstract Background Much attention has recently focused on nutraceuticals which are widely used to promote health. In particular, nutraceuticals with minimal side effects have been developed for preventing or treating neurological diseases such as Alzheimer’s disease (AD). The present study was conducted to investigate the potential effect on neural development and function of the microalgae Aurantiochytrium sp. as a nutraceutical. Methods To test the neuroprotection of ethanol extract of Aurantiochytrium (EEA) and n-Hex layer of EEA (HEEA), amyloid-beta (Aβ)-stimulated SH-SY5Y cells was used for in vitro AD model. We then assessed the enhancement of neurogenesis of EEA and HEEA using murine ex vivo neurospheres. We also administered EEA or HEEA to SAMP8 mice, a non-transgenic strain with accelerated aging and Alzheimer’s-like memory loss for evaluation of spatial learning and memory using MWM test. Finally, we performed immunohistochemical analysis using mice brain fed with EEA for assessment of neurogenesis. Results Pre-treatment of SH-SY5Y cells with EEA or the squalene-rich fraction of EEA, n-Hex layer (HEEA), ameliorated Aβ-induced cytotoxicity. Interestingly, only EEA-treated cells showed a significant increase in cell metabolism and intracellular ATP production. Moreover, EEA treatment significantly increased the number of neurospheres, whilst HEEA treatment significantly increased the number of β-III-tubulin + young neurons and GFAP + astrocytes. SAMP8 mice were given 50 mg/kg EEA or HEEA orally for 30 days. Learning ability was assessed in the Morris water maze test. EEA and HEEA decreased escape latency time in SAMP8 mice, indicating improved memory. To detect activated stem cells and newborn neurons, we administered BrdU for 9 days and measured BrdU + cells in the dentate gyrus, a neurogenic stem cell niche of the hippocampus. In SAMP8 mice, EEA rapidly and significantly increased the number of BrdU + GFAP + stem cells as well as their progeny, BrdU + NeuN + mature neurons. Conclusions Our data in aggregate indicate that EEA and its constituents could be developed into a nutraceutical for promoting brain health and function against some age-related diseases including neurodegenerative desease, particularly AD.

scholarly journals Angiostrongylus cantonensis causes cognitive impairments in heavily infected BALB/c and C57BL/6 mice

2019 ◽  
Author(s):  
Kai-Yuan Jhan ◽  
Guan-Jhih Lai ◽  
Pi-Kai Chang ◽  
Ren-Yu Tang ◽  
Chien-Ju Cheng ◽  
...  
Keyword(s):  
Survival Rate ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Post Infection ◽  
Survival Rates ◽  
Morris Water Maze Test ◽  
Parasitic Infections ◽  
Spatial Learning And Memory ◽  
Dietary Consumption ◽  
Behavior Learning

Abstract BackgroundParasitic infections may cause significant effects on behavior, learning, and memory of the hosts. In the brain of mice heavily infected with Angiostrongylus cantonensis, severe damages have been observed in the hippocampus. This component has been considered to have associations with spatial learning and memory in human and vertebrates. This study was designed to determine the impairments in behavior, learning, and memory in BALB/c and C57BL/6 mice heavily infected with the parasite.MethodsEach mouse was inoculated with 50 third-stage larvae of A. cantonensis. After infection, daily changes in weight and dietary consumption, worm recoveries and survival rates were determined. The forced swimming test, open field test, and Morris water maze test were employed to evaluate depression- and anxiety-like behavior as well as impairments in spatial learning and memory, respectively. In addition, in the two strains of mice were also determined.ResultsThe worm recovery rate in the BALB/c mice was significantly lower than that of C57BL/6 mice since day 14 post-infection. The survival rate in infected BALB/c mice decreased to 0% by day 25 whereas those with swim-training survived three more days. On day 42, the C57BL/6 mice had a survival rate of 85.7% in the swimming group and 70% in the non-swimming group. Significant differences were found in weight between infected and non-infected BALB/c and C57BL/6 mice since day 13 and day 12, respectively with corresponding changes in the dietary consumption. Depression-like behavior was found in the infected BALB/c mice but not in C57BL/6 mice. However, anxiety-like behavior was found to occur only in C57BL/6 mice. Impaired spatial learning and memory were also found in the two strains of mice occurred since day 14 post-infection.ConclusionsResults of this study indicate that A. cantonensis causes depression, anxiety, and impairments in spatial learning and memory in heavily infected mice. Moreover, significantly higher severity was observed in the Th-2 dominant BALB/c mice.

scholarly journals Spatial learning and memory deficits induced by prenatal glucocorticoid exposure depend on hippocampal CRHR1 and CXCL5 signaling in rats

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
You Zheng ◽  
Yan-Min Zhang ◽  
Zheng-Shan Tang ◽  
Jian-Kui Du ◽  
De-Wei Guo ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Memory Deficits ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
Synapsin I ◽  
Postnatal Life ◽  
Pregnant Rats ◽  
Learning And Memory Deficits

Abstract Background Prenatal synthetic glucocorticoid (sGC) exposure increases the susceptibility to cognitive and affective disorders in postnatal life. We previously demonstrated that prenatal sGC exposure results in an increase in corticotropin-releasing hormone (CRH) receptor type 1 (CRHR1) expression in the hippocampus of rats, and CRHR1 is involved in synapse formation via regulation of C-X-C chemokine ligand 5 (CXCL5) in hippocampus. We sought to investigate that the roles of CRHR1 and CXCL5 in learning and memory impairment caused by prenatal sGC exposure. Methods Pregnant rats were administered with saline or dexamethasone (DEX) from gestational day (GD) 14 to GD21. DEX offspring at 2-day old were treated with saline and CRHR1 antagonists (antalarmin and CP154526) for 7 days. Some DEX offspring received intra-hippocampal injection of AAV9 carrying CXCL5 gene. Spatial learning and memory was assessed by Morris water maze test. Immunofluorescence analysis was applied to show synapsin I and PSD95 signals in hippocampus. Synapsin I and PSD95 protein level and CXCL5 concentration were determined by western blotting and ELISA, respectively. Organotypic hippocampal slice cultures were used to investigate the effect of DEX on CXCL5 production in vitro. Results Both male and female DEX offspring displayed impairment of spatial learning and memory in adulthood. Synapsin I and PSD95 signals and CXCL5 levels were decreased in DEX offspring. DEX offspring with antalarmin and CP154526 treatment showed improved spatial learning and memory. Antalarmin and CP154526 treatment increased synapsin I and PSD95 signals and CXCL5 concentration in hippocampus. Bilaterally hippocampal injection of AAV9 carrying CXCL5 gene improved the spatial learning and memory and increased CXCL5 concentration and synapsin I and PSD95 levels in hippocampus. DEX dose-dependently suppressed CXCL5 production in cultured hippocammpal slices, which was prevented by antalarmin treatment. Conclusion CRHR1 and CXCL5 signaling in the hippocampus are involved in spatial learning and memory deficits caused by prenatal DEX exposure. CRHR1 activation contributes to decreased CXCL5 production in hippocampus induced by prenatal DEX treatment. Our study provides a molecular basis of prenatal GC exposure programming spatial learning and memory.

Ameliorating Ribosylation-Induced Amyloid-β Pathology by Berberine via Inhibiting mTOR/p70S6K Signaling

2020 ◽  
pp. 1-12
Author(s):  
Yang-Yang Wang ◽  
Qian Yan ◽  
Zhen-Ting Huang ◽  
Qian Zou ◽  
Jing Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Early Stage ◽  
Amyloid Β ◽  
Mtor Signaling ◽  
Immunofluorescence Staining ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
Aβ Production

Background: Berberine (BBR) plays a neuroprotective role in the pathogenesis of Alzheimer’s disease (AD), inhibiting amyloid-β (Aβ) production and promoting Aβ clearance. Advanced glycation end products (AGEs) promote Aβ aggregation and tau hyperphosphorylation. The activation of mTOR signaling occurring at the early stage of AD has a prominent impact on the Aβ production. This work focused on whether BBR regulates the production and clearance of ribosylation-induced Aβ pathology via inhibiting mTOR signaling. Objective: To explore whether BBR ameliorates ribosylation-induced Aβ pathology in APP/PS1 mice. Methods: Western blot and immunofluorescence staining were used to detect the related proteins of the mammalian target of Rapamycin (mTOR) signaling pathway and autophagy, as well as the related kinases of Aβ generation and clearance. Tissue sections and Immunofluorescence staining were used to observe Aβ42 in APP/PS1 mice hippocampal. Morris water maze test was used to measure the spatial learning and memory of APP/PS1 mice. Results: BBR improves spatial learning and memory of APP/PS1 mice. BBR limits the activation of mTOR/p70S6K signaling pathway and enhances autophagy process. BBR reduces the activity of BACE1 and γ-secretase induced by D-ribose, and enhances Aβ-degrading enzymes and Neprilysin, and inhibits the expression of Aβ in APP/PS1 mice. Conclusion: BBR ameliorates ribosylation-induced Aβ pathology via inhibiting mTOR/p70S6K signaling and improves spatial learning and memory of the APP/PS1 mice.

Sign in / Sign up

Export Citation Format

Share Document