Brominated flame retardant TBPH induced oxidative damage and reduced the expression of memory-related proteins in mice, with no discernable impairment of learning and memory

2021 ◽  
pp. 096032712110588
Author(s):  
Zhang Bao ◽  
Yin Jing
Keyword(s):  
Oxidative Damage ◽  
Learning And Memory ◽  
Flame Retardants ◽  
Camp Response Element Binding ◽  
Oral Exposure ◽  
Neuroprotective Effects ◽  
Stress Markers ◽  
Neurobehavioral Function ◽  
Neurotoxic Effects ◽  
Element Binding Protein

Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) is one of the new brominated flame retardants with adverse neurobehavioral potential. These flame retardants are often added to household furnishings where children would come into contact with them. This study explores whether oral exposure to TBPH for 28 days would impair neurobehavioral function in mice and the role of curcumin (CUR) in this process. CUR is a natural antioxidant and is thought to be of use in the treatment of neurological toxicity due to its neuroprotective effects. Learning and memory of mice exposed to TBPH was investigated using the Morris water maze. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were determined to assess oxidative damage. Western blot was used to detect the expression of glucose-regulated protein 78-kDa (GRP78), PKR-like ER kinase (PERK), and C/EBP homologous protein (CHOP) in the hippocampus. End-point effects were evaluated through observing post-synaptic density protein-95 (PSD-95), brain-derived neurotrophic factor (BDNF), and phosphorylated cAMP response element binding protein (p-CREB). Although TBPH exposure alone does not impair learning and memory, oxidative stress markers and endoplasmic reticulum stress–associated proteins were adversely affected in exposed mice. TBPH could significantly decrease the levels of BDNF, p-CREB, and PSD-95 in the hippocampus, and these TBPH-induced neurotoxic effects were attenuated by CUR. These findings provide further understanding of the neurotoxic effects of TBPH and the protective effect of CUR on TBPH exposure.

scholarly journals Low Dose of Valproate Improves Motor Function after Traumatic Brain Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yu-Ting Tai ◽  
Wen-Yuan Lee ◽  
Fei-Peng Lee ◽  
Tien-Jen Lin ◽  
Chia-Lin Shih ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Brain Injuries ◽  
The United States ◽  
Camp Response Element Binding ◽  
Pharmacological Intervention ◽  
Neuroprotective Effects ◽  
Adult Rats ◽  
Protein Activation ◽  
Element Binding Protein ◽  
High Doses

Background.Traumatic brain injuries (TBIs) are a major health care problem worldwide. Approximately 1.5 million new TBI cases occur annually in the United States, with mortality rates ranging between 35% and 40% in severe patients. Despite the incidence of these injuries and their substantial socioeconomic implications, no specific pharmacological intervention is available for clinical use. Several studies have indicated that 300 mg/kg or 400 mg/kg of valproate (VPA) exhibits neuroprotective effects in animal models. However, humans cannot tolerate high doses of VPA. This study aims to investigate whether 30 mg/kg of VPA administered to rats affects TBIs.Methods.We used a rat model to test the effects of 30 mg/kg of VPA on TBIs. Molecular identifications for histone acetylation and phosphorylation of cAMP response element-binding protein (CREB) and phosphorylated extracellular signal regulated kinase (ERK) were performed.Results.The results indicated that treating adult rats with VPA after TBIs significantly decreased the contusion volume and recovery of contusion-related skilled forelimb reaching deficits. Applying VPA also increased histone acetylation, p-ERK, and p-CREB expression in the brain. Furthermore, applying VPA reduced inflammation, glial fibrillary acidic protein activation, and apoptosis.Conclusion.This study found that 30 mg/kg of VPA assists in treating TBIs in rat models.

scholarly journals Effects of Caloric Intake on Learning and Memory Function in Juvenile C57BL/6J Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Bao-Lei Xu ◽  
Rong Wang ◽  
Li-Na Ma ◽  
Wen Dong ◽  
Zhi-Wei Zhao ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Memory Function ◽  
Caloric Intake ◽  
Camp Response Element Binding ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Downstream Effectors ◽  
Element Binding Protein

Dietary composition may influence neuronal function as well as processes underlying synaptic plasticity. In this study, we aimed to determine the effect of high and low caloric diets on a mouse model of learning and memory and to explore mechanisms underlying this process. Mice were divided into three different dietary groups: normal control(n=12), high-caloric (HC) diet(n=12), and low-caloric (LC) diet(n=12). After 6 months, mice were evaluated on the Morris water maze to assess spatial memory ability. We found that HC diet impaired learning and memory function relative to both control and LC diet. The levels of SIRT1 as well as its downstream effectors p53, p16, and peroxisome proliferator-activated receptorγ(PPARγ) were decreased in brain tissues obtained from HC mice. LC upregulated SIRT1 but downregulated p53, p16, and PPARγ. The expressions of PI3K and Akt were not altered after HC or LC diet treatment, but both LC and HC elevated the levels of phosphorylated-cAMP response element-binding protein (p-CREB) and IGF-1 in hippocampal CA1 region. Therefore, HC diet-induced dysfunction in learning and memory may be prevented by caloric restriction via regulation of the SIRT1-p53 or IGF-1 signaling pathways and phosphorylation of CREB.

Rolipram rescues memory consolidation deficits caused by sleep deprivation: Implication of the cAMP/PKA and cAMP/Epac pathways

2021 ◽  
Vol 20 ◽  
Author(s):  
Ahmed Maher ◽  
Nesrine El Sayed ◽  
Heba Nafea ◽  
Mohamed Gad
Keyword(s):  
Sleep Deprivation ◽  
Learning And Memory ◽  
Glycogen Synthase ◽  
Memory Deficits ◽  
Camp Response Element Binding ◽  
Brain Inflammation ◽  
Pde4 Inhibitor ◽  
Negative Effects ◽  
Element Binding Protein ◽  
Dual Mechanism

Background: Over the last few years, the number of people suffering from sleeping disorders has increased significantly despite negative effects on cognition and an association with brain inflammation. Objectives: We assessed memory deficits caused by sleep deprivation (SD) to determine the therapeutic effect of phosphodiesterase 4 (PDE4) inhibitors on SD-induced memory deficits and to investigate whether the modulation of memory deficits by PDE4 inhibitors is mediated by a protein kinase A (PKA)-independent pathway in conjunction with a PKA-dependent pathway. Methods: Adult male mice were divided into four groups. Three SD groups were deprived of Rapid eye movement (REM) sleep for 12 h a day for six consecutive days. They were tested daily in the Morris water maze to evaluate learning and memory. One of the SD groups was injected with a PDE4 inhibitor, rolipram (1 mg/kg ip), whereas another had rolipram co-administered with chlorogenic acid (CHA, 20 mg/kg ip), an inhibitor of PKA. After 6 days, the mice were sacrificed, and the hippocampi were evaluated for cyclic AMP (cAMP) and nuclear factor Nrf-2 levels. The hippocampal expression of PKA, phosphorylated cAMP response element-binding protein (CREB), and phosphorylated glycogen synthase 3β (Ser389) were also evaluated. Results: SD caused a significant decrease in cAMP levels in the brain and had a detrimental effect on learning and memory. The administration of rolipram or rolipram+CHA resulted in an improvement in cognitive function. Conclusion: The present study provides evidence that restoration of memory with PDE4 inhibitors occurs through a dual mechanism involving the PKA and Epac pathways.

scholarly journals Effects of Ketamine on Learning and Memory in the Hippocampus of Rats through ERK, CREB, and Arc

2020 ◽  
Vol 11 (1) ◽  
pp. 27
Author(s):  
Mingxian Shi ◽  
Jiafeng Ding ◽  
Lin Li ◽  
Hui Bai ◽  
Xinran Li ◽  
...  
Keyword(s):  
Protein Expression ◽  
Learning And Memory ◽  
Dose Group ◽  
Camp Response Element Binding ◽  
Morris Water Maze Test ◽  
Memory Ability ◽  
Expression Levels ◽  
Element Binding Protein ◽  
High Level ◽  
Arc Gene

Ketamine has become a popular recreational drug due to its neuronal anesthesia effect and low price. The process of learning and memory is part of the distinctive high-level neural activities in animals. We investigated the effects of subanesthetic and anesthetic doses of ketamine on the learning and memory-related signal transduction mechanisms. We used the Morris water maze test to execute rats’ learning and memory ability and detected changes of Arc mRNA and Arc, cAMP-response element-binding protein (CREB), phospho-CREB (p-CREB), extracellular signal-regulated kinase (ERK), and phospho-ERK (p-ERK) protein expression in the hippocampus 10 min and 24 h after administration. Ten min after ketamine injection, the Arc gene and the protein expression levels increased in all groups; p-ERK only increased in the chronic subanesthetic dose group. After 24 h, the Arc gene and the protein expression levels of the subanesthetic dose group increased, but those of the chronic subanesthetic dose group and anesthetic dose group decreased. However, p-ERK increased in all groups. A chronic subanesthetic dose of ketamine could increase learning and memory ability through ERK, CREB, and Arc in a short time, and the high body temperature after the subanesthetic dose of ketamine injection was the main factor leading to changes in Arc. The subanesthetic dose of ketamine regulated learning and memory through ERK, CREB, and ARC 24 h after injection.

scholarly journals Flavones 7,8-DHF, Quercetin, and Apigenin Against Tau Toxicity via Activation of TRKB Signaling in ΔK280 TauRD-DsRed SH-SY5Y Cells

2021 ◽  
Vol 13 ◽  
Author(s):  
Ni-Ni Chiang ◽  
Te-Hsien Lin ◽  
Yu-Shan Teng ◽  
Ying-Chieh Sun ◽  
Kuo-Hsuan Chang ◽  
...  
Keyword(s):  
Cellular Response ◽  
Memory Loss ◽  
Treatment Strategies ◽  
Camp Response Element Binding ◽  
Neuroprotective Effects ◽  
Downstream Signaling ◽  
Element Binding Protein ◽  
Tropomyosin Related Kinase B ◽  
New Treatment ◽  
Tau Aggregation

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with memory loss and cognitive decline. Neurofibrillary tangles (NFTs) formed by hyperphosphorylated Tau protein are one of the pathological hallmarks of several neurodegenerative diseases including AD. Heat shock protein family B (small) member 1 (HSPB1) is a molecular chaperone that promotes the correct folding of other proteins in response to environmental stress. Nuclear factor erythroid 2-like 2 (NRF2), a redox-regulated transcription factor, is the master regulator of the cellular response to excess reactive oxygen species. Tropomyosin-related kinase B (TRKB) is a membrane-bound receptor that, upon binding brain-derived neurotrophic factor (BDNF), phosphorylates itself to initiate downstream signaling for neuronal survival and axonal growth. In this study, four natural flavones such as 7,8-dihydroxyflavone (7,8-DHF), wogonin, quercetin, and apigenin were evaluated for Tau aggregation inhibitory activity and neuroprotection in SH-SY5Y neuroblastoma. Among the tested flavones, 7,8-DHF, quercetin, and apigenin reduced Tau aggregation, oxidative stress, and caspase-1 activity as well as improved neurite outgrowth in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. Treatments with 7,8-DHF, quercetin, and apigenin rescued the reduced HSPB1 and NRF2 and activated TRKB-mediated extracellular signal-regulated kinase (ERK) signaling to upregulate cAMP-response element binding protein (CREB) and its downstream antiapoptotic BCL2 apoptosis regulator (BCL2). Knockdown of TRKB attenuated the neuroprotective effects of these three flavones. Our results suggest 7,8-DHF, quercetin, and apigenin targeting HSPB1, NRF2, and TRKB to reduce Tau aggregation and protect cells against Tau neurotoxicity and may provide new treatment strategies for AD.

scholarly journals Electroacupuncture Ameliorates Learning and Memory via Activation of the CREB Signaling Pathway in the Hippocampus to Attenuate Apoptosis after Cerebral Hypoperfusion

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaohua Han ◽  
Xiuxiu Zhao ◽  
Min Lu ◽  
Fang Liu ◽  
Feng Guo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Learning And Memory ◽  
Camp Response Element Binding ◽  
Cerebral Hypoperfusion ◽  
Spatial Learning And Memory ◽  
Morris Water Maze Task ◽  
Element Binding Protein ◽  
Blotting Technique ◽  
Ca1 Area ◽  
Improved Learning

Studies have shown that electroacupuncture (EA) ameliorates learning and memory after ischemic injury. However, there have been few studies elucidating the mechanisms of EA on learning and memory in cerebral hypoperfusion. In this study, we explored the cAMP response element-binding protein (CREB) signaling pathway-mediated antiapoptotic action involved in EA-induced improvement of learning and memory. EA at GV20 and GV14 acupoints was applied in cerebral hypoperfusion rats. A Morris water maze task was performed, and the immunoreactivities of pCREB, Bcl-2, and Bax in the hippocampal CA1 area were evaluated by the Western blotting technique. Our findings indicated that (1) EA ameliorated spatial learning and memory impairment in cerebral hypoperfusion rats; (2) EA increased the immunoreactivities of pCREB and Bcl-2 and decreased the immunoreactivity of Bax; (3) intracerebroventricular administration of H89 (the inhibitor of protein kinase A) blocked EA-induced, pCREB-mediated antiapoptotic action and improved learning and memory. These results suggest that EA can ameliorate learning and memory via activation of the CREB signaling pathway in the hippocampus to attenuate apoptosis after cerebral hypoperfusion.

scholarly journals Alogliptin Attenuates Lipopolysaccharide-Induced Neuroinflammation in Mice Through Modulation of TLR4/MYD88/NF-κB and miRNA-155/SOCS-1 Signaling Pathways

2020 ◽  
Author(s):  
Ayman E El-Sahar ◽  
Nesma A Shiha ◽  
Nesrine S El Sayed ◽  
Lamiaa A Ahmed
Keyword(s):  
Nuclear Factor Κb ◽  
Camp Response Element Binding ◽  
Primary Response ◽  
Myeloid Differentiation ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Camp Response Element ◽  
Toll Like Receptor 4 ◽  
Neuroprotective Effects ◽  
Element Binding Protein

Abstract Background Endotoxin-induced neuroinflammation plays a crucial role in the pathogenesis and progression of various neurodegenerative diseases. A growing body of evidence supports that incretin-acting drugs possess various neuroprotective effects that can improve learning and memory impairments in Alzheimer’s disease models. Thus, the present study aimed to investigate whether alogliptin, a dipeptidyl peptidase-4 inhibitor, has neuroprotective effects against lipopolysaccharide (LPS)-induced neuroinflammation and cognitive impairment in mice as well as the potential mechanisms underlying these effects. Methods Mice were treated with alogliptin (20 mg/kg/d; p.o.) for 14 days, starting 1 day prior to intracerebroventricular LPS injection (8 μg/μL in 3 μL). Results Alogliptin treatment alleviated LPS-induced cognitive impairment as assessed by Morris water maze and novel object recognition tests. Moreover, alogliptin reversed LPS-induced increases in toll-like receptor 4 and myeloid differentiation primary response 88 protein expression, nuclear factor-κB p65 content, and microRNA-155 gene expression. It also rescued LPS-induced decreases in suppressor of cytokine signaling gene expression, cyclic adenosine monophosphate (cAMP) content, and phosphorylated cAMP response element binding protein expression in the brain. Conclusion The present study sheds light on the potential neuroprotective effects of alogliptin against intracerebroventricular LPS-induced neuroinflammation and its associated memory impairment via inhibition of toll-like receptor 4/ myeloid differentiation primary response 88/ nuclear factor-κB signaling, modulation of microRNA-155/suppressor of cytokine signaling-1 expression, and enhancement of cAMP/phosphorylated cAMP response element binding protein signaling.

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