scholarly journals SerpinA3N deficiency deteriorates impairments of learning and memory in mice following hippocampal stab injury

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Zhi-Meng Wang ◽  
Cong Liu ◽  
Ying-Ying Wang ◽  
Yu-Sen Deng ◽  
Xuan-Cheng He ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Hippocampal Neurons ◽  
Neuronal Apoptosis ◽  
Early Stage ◽  
Critical Role ◽  
Specific Inhibitor ◽  
Serine Protease Inhibitor ◽  
Therapeutic Agents ◽  
Spatial Learning And Memory ◽  
Stab Injury

Abstract Traumatic brain injury is a global leading cause of disability and death, which puts patients at high risk for developing dementia. Early intervention is believed as the key to minimize the development of brain damages that could aggravate the symptoms. Here, we report that the serine protease inhibitor SerpinA3N is upregulated in hippocampal neurons in the early stage of hippocampal stab injury (HSI), while its deficiency causes a greater degree of neuronal apoptosis and severer impairments of spatial learning and memory in mice after HSI. We further show that MMP2 is a key substrate of SerpinA3N, and MMP2 specific inhibitor (ARP100) can protect against neuronal apoptosis and cognitive dysfunction in mice after HSI. These findings demonstrate a critical role for SerpinA3N in neuroprotection, suggesting that SerpinA3N and MMP2 inhibitors might be a novel therapeutic agents for neurotrauma.

scholarly journals S-adenosylmethionine Decarboxylase 1 Participates in PM2.5 Exposure Induced Neuronal Apoptosis via Mitochondria-Mediated Pathway

2020 ◽  
Author(s):  
Xiaozheng Zhu ◽  
Yikai Shou ◽  
Xintong Ji ◽  
Yu Hu ◽  
Huanhuan Wang
Keyword(s):  
Neurodegenerative Diseases ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurons ◽  
Neuronal Apoptosis ◽  
Mitochondrial Pathway ◽  
Whole Body ◽  
Spatial Learning And Memory ◽  
Apoptosis Pathway ◽  
Adenosylmethionine Decarboxylase

Abstract Background: Fine particle (Particulate matter 2.5, PM2.5), as the primary ambient pollutant, is considered harmful to some neurodegenerative diseases, while the specific biochemical mechanism underlying is still unrevealed. Neuronal apoptosis is believed the crucial event in neurodegenerative pathogenesis, but evidence supporting neuronal apoptosis as PM2.5 induced neuronal injury is insufficient. S-adenosylmethionine decarboxylase 1 (AMD1) and its related spermidine synthesis have been shown to participate in cellular apoptosis, but its role in PM2.5 exposure induced neuronal apoptosis was rarely reported. To better understand contribution of AMD1 activity and spermidine in PM2.5 exposure induced neuronal apoptosis, may provide novel therapeutic and preventive targets for air pollution associated neurodegenerative diseases.Methods: In the current work, sixteen C57BL/6 male mice were randomly divided into ambient PM2.5 chamber or filtered air chamber, and the mouse model of whole-body ambient PM2.5 chronic exposure was established. Behavioral and cognitive ability, together with corresponding biomedical index were recorded and tested to evaluated neurotoxicity by PM2.5 exposure in mice. In parallel, PC12 cells and primary hippocampal neurons were applied for PM2.5 treatment to explore the possible cellular and molecular mechanism which may be critically involved in the process. AMD1 activity and cellular spermidine content were modulated by pharmacological approach to examine their participation in PM2.5 triggered neuronal apoptosis, followed by better examination of typical index for mitochondrial membrane potential and mitochondrial-mediated apoptosis pathway signaling.Results: Chronic ambient PM2.5 exposure attenuated spatial learning and memory ability, and triggered neuronal apoptosis together with increased expression of apoptosis-related Bax/Bcl-2 and cleaved caspase-3. PM2.5 exposure impaired AMD1 expression and spermidine synthesis. AMD1 inhibition could mimick PM2.5 exposure induced neuronal apoptosis. Spermidine supplementation rescued against neurotoxicity and inhibited PM2.5 induced apoptosis, in which mitochondrial pathway signaling.Conclusions: Chronic real-time exposure to ambient PM2.5 led to the reduced the ability of spatial learning and memory in mice. Neuronal apoptosis was the key event in the process of neurodegenerative development induced by PM2.5 exposure. AMD1 and spermidine participated in neuronal apoptosis induced by PM2.5 exposure, which was at least partially dependent on mitochondria mediated pathway.

scholarly journals Pgrmc1/BDNF Signaling Plays a Critical Role in Mediating Glia-Neuron Cross Talk

Endocrinology ◽  
2016 ◽  
Vol 157 (5) ◽  
pp. 2067-2079 ◽  
Author(s):  
Fen Sun ◽  
Trinh Nguyen ◽  
Xin Jin ◽  
Renqi Huang ◽  
Zhenglan Chen ◽  
...  
Keyword(s):  
Cross Talk ◽  
Hippocampal Neurons ◽  
Brain Slice ◽  
Critical Role ◽  
Specific Inhibitor ◽  
Neurotrophin Receptor ◽  
Bdnf Signaling ◽  
Brain Slice Cultures ◽  
Enriched Cultures ◽  
Retinoid Acid

Abstract Progesterone (P4) exerts robust cytoprotection in brain slice cultures (containing both neurons and glia), yet such protection is not as evident in neuron-enriched cultures, suggesting that glia may play an indispensable role in P4's neuroprotection. We previously reported that a membrane-associated P4 receptor, P4 receptor membrane component 1, mediates P4-induced brain-derived neurotrophic factor (BDNF) release from glia. Here, we sought to determine whether glia are required for P4's neuroprotection and whether glia's roles are mediated, at least partially, via releasing soluble factors to act on neighboring neurons. Our data demonstrate that P4 increased the level of mature BDNF (neuroprotective) while decreasing pro-BDNF (potentially neurotoxic) in the conditioned media (CMs) of cultured C6 astrocytes. We examined the effects of CMs derived from P4-treated astrocytes (P4-CMs) on 2 neuronal models: 1) all-trans retinoid acid-differentiated SH-SY5Y cells and 2) mouse primary hippocampal neurons. P4-CM increased synaptic marker expression and promoted neuronal survival against H2O2. These effects were attenuated by Y1036 (an inhibitor of neurotrophin receptor [tropomysin-related kinase] signaling), as well as tropomysin-related kinase B-IgG (a more specific inhibitor to block BDNF signaling), which pointed to BDNF as the key protective component within P4-CM. These findings suggest that P4 may exert its maximal protection by triggering a glia-neuron cross talk, in which P4 promotes mature BDNF release from glia to enhance synaptogenesis as well as survival of neurons. This recognition of the importance of glia in mediating P4's neuroprotection may also inform the design of effective therapeutic methods for treating diseases wherein neuronal death and/or synaptic deficits are noted.

scholarly journals Environmental Enrichment Attenuated Sevoflurane-Induced Neurotoxicity through the PPAR-γSignaling Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Yupeng Zhao ◽  
Kaizheng Chen ◽  
Xia Shen
Keyword(s):  
Signaling Pathway ◽  
Learning And Memory ◽  
Memory Impairment ◽  
Neuronal Apoptosis ◽  
Environmental Enrichment ◽  
Memory Function ◽  
Critical Role ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Peroxisome Proliferator ◽  
Young Mice

Sevoflurane is the most widely used inhaled anesthetic. Environmental enrichment (EE) can reverse sevoflurane-induced learning and memory impairment in young mice. However, the mechanism by which EE elicits this effect is unclear. The peroxisome proliferator-activated receptor (PPAR) regulatory pathway plays a critical role in the regulation of inflammation in central nervous system diseases. In this study, we investigated whether EE attenuates sevoflurane-induced learning and memory disability via the PPAR signaling pathway. Six-day-old mice were treated with 3% sevoflurane for 2 hours daily from postnatal day 6 (P6) to P8. Then, the mice were treated with EE. The effects of sevoflurane on learning and memory function, PPAR-γexpression in the brain, and the numbers of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and 5-bromodeoxyuridine-positive cells in the hippocampus were determined. Sevoflurane induced neuronal apoptosis and neurogenesis inhibition, which may impair learning and memory in young mice. Furthermore, sevoflurane downregulated PPAR-γexpression. Both EE and the PPAR-γagonist, rosiglitazone, attenuated sevoflurane-induced neuronal apoptosis, neurogenesis inhibition, and learning and memory impairment. Our findings suggest that EE ameliorated sevoflurane-induced neurotoxicity and learning and memory impairment through the PPAR-γsignaling pathway. PPAR-γmay be a potential therapeutic target for preventing or treating sevoflurane-induced neurotoxicity.

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.

scholarly journals Ameliorating Ribosylation-induced Aβ Pathology by Berberine via Inhibiting mTOR/p70S6K Signaling

2020 ◽  
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 ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Immunofluorescence Staining ◽  
Spatial Learning And Memory ◽  
Aβ Generation ◽  
Aβ Production

Abstract Background: Berberine (BBR) plays a neuroprotective role in the pathogenesis of Alzheimer’s disease (AD), inhibiting β-amyloid (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.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 Aβ1-42 in APP/PS1 mice hippocampal. Morris water maze (MWM) 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 BACE1and γ-secretase induced by D-ribose, and enhances Aβ-degrading enzymes and Neprilysin, and inhibits the expression of Aβin APP/PS1 mice.Conclusions: BBR ameliorates ribosylation-induced Aβ pathology via inhibiting mTOR/p70S6K signaling, and improves spatial learning and memory of the APP/PS1 mice.

scholarly journals The Effects of Intraoperative Hypothermia on Postoperative Cognitive Function in the Rat Hippocampus and Its Possible Mechanisms

2022 ◽  
Vol 12 (1) ◽  
pp. 96
Author(s):  
Guangyan Xu ◽  
Tianjia Li ◽  
Yuguang Huang
Keyword(s):  
Working Memory ◽  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurons ◽  
Spatial Working Memory ◽  
Postoperative Cognitive Dysfunction ◽  
Spatial Learning And Memory ◽  
Intraoperative Hypothermia

Intraoperative hypothermia is a common complication during operations and is associated with several adverse events. Postoperative cognitive dysfunction (POCD) and its adverse consequences have drawn increasing attention in recent years. There are currently no relevant studies investigating the correlation between intraoperative hypothermia and POCD. The aim of this study was to assess the effects of intraoperative hypothermia on postoperative cognitive function in rats undergoing exploratory laparotomies and to investigate the possible related mechanisms. We used the Y-maze and Morris Water Maze (MWM) tests to assess the rats’ postoperative spatial working memory, spatial learning, and memory. The morphological changes in hippocampal neurons were examined by haematoxylin-eosin (HE) staining and hippocampal synaptic plasticity-related protein expression. Activity-regulated cytoskeletal-associated protein (Arc), cyclic adenosine monophosphate-response element-binding protein (CREB), S133-phosphorylated CREB (p-CREB [S133]), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor 1 (AMPAR1), and S831-phosphorylated AMPAR1 (p-AMPAR1 [S831]) were evaluated by Western blotting. Our results suggest a correlation between intraoperative hypothermia and POCD in rats and that intraoperative hypothermia may lead to POCD regarding impairments in spatial working memory, spatial learning, and memory. POCD induced by intraoperative hypothermia might be due to hippocampal neurons damage and decreased expression of synaptic plasticity-related proteins Arc, p-CREB (S133), and p-AMPAR1 (S831).

scholarly journals Spatial learning and memory of young and aging rats following injection with human Wharton’s jelly‐mesenchymal stem cells

2021 ◽  
Vol 26 (2) ◽  
pp. 91
Author(s):  
Berry Juliandi ◽  
Wildan Mubarok ◽  
Dian Anggraini ◽  
Arief Boediono ◽  
Mawar Subangkit ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Neuronal Apoptosis ◽  
Spatial Learning And Memory ◽  
Post Injection ◽  
Aging Rats ◽  
Wharton's Jelly ◽  
Young Rats

Human Wharton’s jelly‐mesenchymal stem cells (hWJ‐MSC) are an emerging potential source of stem cells derived from the umbilical cord. Previous studies have shown their potential as treatment for traumatic brain injury and Parkinson’s disease. However, no study has yet investigated the effect of hWJ‐MSC injections in countering spatial learning and memory impairment in aging rats. The effect of hWJ‐MSC injection on young rats is also unknown. The objective of this research was to analyze the effect of an hWJ‐MSC injection on spatial learning, memory, density of putative neural progenitor cells (pNPC), and neuronal apoptosis in the dentate gyrus (DG) of young and aging rats. Injection of hWJ‐MSC did not change spatial learning and memory in young rats until two months post‐injection. This might be due to retained pNPC density and neuronal apoptosis in the DG of young rats after injection of hWJ‐MSC. In contrast, injection of hWJ‐MSC promoted both spatial learning and memory in aging rats, a finding that might be attributable to the increased pNPC density and attenuated neuronal apoptosis in DG of aging rats during the two months post‐injection. Our study suggests that a single injection of hWJ‐MSC might be sufficient to promote improvement in long‐term learning and memory in aging rats.

scholarly journals Early-life Psychological Stress Leads to Impaired Spatial Learning and Memory and Alters Hippocampal Proteome in Adult Rats

2021 ◽  
Author(s):  
Lin Han ◽  
Xiaofan Xiong ◽  
Meiyang Fan ◽  
Lingyu Zhang ◽  
Liying Liu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Learning And Memory ◽  
Psychological Stress ◽  
Spatial Learning ◽  
Early Life ◽  
Adult Stage ◽  
Early Stage ◽  
The Other ◽  
Spatial Learning And Memory ◽  
Adult Rats

Abstract Early-life psychological stress (ELPS) can cause anxiety, pessimism, and a decrease of cognitive ability in adult individuals. In this study, a psychological stress model (a terrified sound stress) was applied to new-born Sprague-Dawley rats for 21 days. And then, we separately evaluated the impact of ELPS on their spatial learning and memory abilities and hippocampal proteome from early-stage to the adult-stage. The Morris Water Maze (MWM) test was employed to evaluate their spatial learning and memory abilities after ELPS till to the adult-stage. Two-dimensional gel electrophoresis (2DE) as well as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were used to uncover the protein expression profile of the hippocampus from both ELPS-young and ELPS-adult as well as their control groups. We found that the rats had a dysfunction of spatial learning and memory after the ELPS till to the adult-stage. The proteomic analysis revealed that 51 proteins were significant differentially expression, and 25 of them were down-regulated, while the other 26 proteins were up-regulated in the hippocampus of the ELPS-young rats compared with the controls. In the ELPS-adult rats, there were 56 significant differentially expression proteins, and 42 of them were down-regulated, the other 14 proteins were up-regulated in the hippocampus compared with their controls. Thirteen of the most significant differentially expressed proteins in ELPS-adult hippocampus were identified as SPTAN1, MYH4, HSPA8, HS90A, DYN1, DLDH, ARP3, GLNA, SAHH, HBB1, ACLY, TBB2A and GBB1, that demonstrated the greatest stress-induced changes. Furthermore, western blotting analyses consistently showed that the reduced expression of SPTAN1 and MYH4 whereas the expression of HSPA8 was up-regulated in the hippocampus after ELPS till to the adult-stage. The current study showed the impaired spatial learning and memory and changed hippocampal gene expressions induced by ELPS from early-stage to adult-stage in rats. This study shows that ELPS plays an important role in behavioral cognition and hippocampal protein expression in adult rats.

scholarly journals Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice

2017 ◽  
Vol 114 (4) ◽  
pp. E619-E628 ◽  
Author(s):  
Chih-Ming Chen ◽  
Lauren L. Orefice ◽  
Shu-Ling Chiu ◽  
Tara A. LeGates ◽  
Samer Hattar ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Neuronal Morphology ◽  
Adult Brain ◽  
Receptor Expression ◽  
Spatial Learning And Memory ◽  
Brain Functions ◽  
Wnt5a Expression

Stability of neuronal connectivity is critical for brain functions, and morphological perturbations are associated with neurodegenerative disorders. However, how neuronal morphology is maintained in the adult brain remains poorly understood. Here, we identify Wnt5a, a member of the Wnt family of secreted morphogens, as an essential factor in maintaining dendritic architecture in the adult hippocampus and for related cognitive functions in mice. Wnt5a expression in hippocampal neurons begins postnatally, and its deletion attenuated CaMKII and Rac1 activity, reduced GluN1 glutamate receptor expression, and impaired synaptic plasticity and spatial learning and memory in 3-mo-old mice. With increased age, Wnt5a loss caused progressive attrition of dendrite arbors and spines in Cornu Ammonis (CA)1 pyramidal neurons and exacerbated behavioral defects. Wnt5a functions cell-autonomously to maintain CA1 dendrites, and exogenous Wnt5a expression corrected structural anomalies even at late-adult stages. These findings reveal a maintenance factor in the adult brain, and highlight a trophic pathway that can be targeted to ameliorate dendrite loss in pathological conditions.

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