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 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 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.

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 Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Zhao Li ◽  
Shuang Zhao ◽  
Hai-Lin Zhang ◽  
Peng Liu ◽  
Fei-Fei Liu ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Neuronal Apoptosis ◽  
Memory Function ◽  
Interleukin 1 ◽  
Spatial Learning And Memory ◽  
Synthesis Inhibitor ◽  
Expression Levels ◽  
Proinflammatory Factor ◽  
Paclitaxel Treatment

The chemotherapeutic agent paclitaxel is widely used for cancer treatment. Paclitaxel treatment impairs learning and memory function, a side effect that reduces the quality of life of cancer survivors. However, the neural mechanisms underlying paclitaxel-induced impairment of learning and memory remain unclear. Paclitaxel treatment leads to proinflammatory factor release and neuronal apoptosis. Thus, we hypothesized that paclitaxel impairs learning and memory function through proinflammatory factor-induced neuronal apoptosis. Neuronal apoptosis was assessed by TUNEL assay in the hippocampus. Protein expression levels of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in the hippocampus tissue were analyzed by Western blot assay. Spatial learning and memory function were determined by using the Morris water maze (MWM) test. Paclitaxel treatment significantly increased the escape latencies and decreased the number of crossing in the MWM test. Furthermore, paclitaxel significantly increased the number of TUNEL-positive neurons in the hippocampus. Also, paclitaxel treatment increased the expression levels of TNF-αand IL-1βin the hippocampus tissue. In addition, the TNF-αsynthesis inhibitor thalidomide significantly attenuated the number of paclitaxel-induced TUNEL-positive neurons in the hippocampus and restored the impaired spatial learning and memory function in paclitaxel-treated rats. These data suggest that TNF-αis critically involved in the paclitaxel-induced impairment of learning and memory function.

scholarly journals Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory

2016 ◽  
Vol 36 (18) ◽  
pp. 4940-4958 ◽  
Author(s):  
Cortney C. Winkle ◽  
Reid H. J. Olsen ◽  
Hyojin Kim ◽  
Sheryl S. Moy ◽  
Juan Song ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurons ◽  
Spatial Learning And Memory

scholarly journals Adulthood Deficiency of the Insulin-like Growth Factor-1 Receptor in Hippocampal Neurons Impairs Cell Structure and Spatial Learning and Memory in Male and Not Female Mice

2021 ◽  
Author(s):  
Cellas A Hayes ◽  
Erik L Hodges ◽  
Jessica P Marshall ◽  
Sreemathi Logan ◽  
Julie A Farley ◽  
...  
Keyword(s):  
Growth Factor ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurons ◽  
Spatial Learning And Memory ◽  
Insulin Like Growth Factor ◽  
Male Mice ◽  
Female Mice ◽  
Learning Impairments ◽  
Increased Risk

Reductions in insulin-like growth factor-1 (IGF-1) are associated with cognitive impairment and increased risk of neurodegenerative disease in advanced age. In mouse models, reduced IGF-1 early-in-life leads to memory impairments and synaptic dysfunction; however, these models are limited by systemic reductions in IGF-1. We hypothesized that IGF-1 continues to promote hippocampal neuron structure and function after development, and as such, the loss of IGF-1 signaling in adult neurons would lead to impaired spatial learning and memory. To test this, the IGF-1 receptor (IGF-1R) was genetically targeted in hippocampal neurons of adult male and female mice. Male mice deficient in neuronal IGF-1R exhibited spatial learning impairments as evidenced by increased pathlength and errors in the radial arm water maze. No differences in learning and memory were observed in female mice. Golgi-Cox staining revealed a reduced number of dendritic boutons of neurons the CA1 region of the hippocampus in male mice. Decreased MAPK and increased ROCK activity were also observed in these tissues. In vitro studies revealed that impaired neurite outgrowth due to inhibited IGF-1R signaling could be rescued by pharmacological inhibitors of ROCK. However, ROCK inhibition in neuronal IGF-1R deficient mice did not fully rescue learning impairments or bouton numbers. Together, our study highlights that IGF-1 continues to support spatial learning and memory and neuronal structure in adulthood.

scholarly journals Deficiency of Intellectual Disability-Related Gene Brpf1 Attenuated Hippocampal Excitatory Synaptic Transmission and Impaired Spatial Learning and Memory Ability

2021 ◽  
Vol 9 ◽  
Author(s):  
Weiwei Xian ◽  
Jingli Cao ◽  
Xiangshan Yuan ◽  
Guoxiang Wang ◽  
Qiuyan Jin ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Synaptic Transmission ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurons ◽  
Dendritic Morphology ◽  
Excitatory Synaptic Transmission ◽  
Spatial Learning And Memory ◽  
Memory Ability ◽  
Cultured Hippocampal Neurons

Patients with monoallelic bromodomain and PHD finger-containing protein 1 (BRPF1) mutations showed intellectual disability. The hippocampus has essential roles in learning and memory. Our previous work indicated that Brpf1 was specifically and strongly expressed in the hippocampus from the perinatal period to adulthood. We hypothesized that mouse Brpf1 plays critical roles in the morphology and function of hippocampal neurons, and its deficiency leads to learning and memory deficits. To test this, we performed immunofluorescence, whole-cell patch clamp, and mRNA-Seq on shBrpf1-infected primary cultured hippocampal neurons to study the effect of Brpf1 knockdown on neuronal morphology, electrophysiological characteristics, and gene regulation. In addition, we performed stereotactic injection into adult mouse hippocampus to knock down Brpf1 in vivo and examined the learning and memory ability by Morris water maze. We found that mild knockdown of Brpf1 reduced mEPSC frequency of cultured hippocampal neurons, before any significant changes of dendritic morphology showed. We also found that Brpf1 mild knockdown in the hippocampus showed a decreasing trend on the spatial learning and memory ability of mice. Finally, mRNA-Seq analyses showed that genes related to learning, memory, and synaptic transmission (such as C1ql1, Gpr17, Htr1d, Glra1, Cxcl10, and Grin2a) were dysregulated upon Brpf1 knockdown. Our results showed that Brpf1 mild knockdown attenuated hippocampal excitatory synaptic transmission and reduced spatial learning and memory ability, which helps explain the symptoms of patients with BRPF1 mutations.

scholarly journals Dendrobium alkaloids prevent Aβ25–35-induced neuronal and synaptic loss via promoting neurotrophic factors expression in mice

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2739 ◽  
Author(s):  
Jing Nie ◽  
Yong Tian ◽  
Yu Zhang ◽  
Yan-Liu Lu ◽  
Li-Sheng Li ◽  
...  
Keyword(s):  
Protein Expression ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Neurotrophic Factors ◽  
Neurotrophic Factor ◽  
Neuronal Apoptosis ◽  
Amyloid Peptide ◽  
Tunel Staining ◽  
Spatial Learning And Memory ◽  
Synaptic Loss

BackgroundNeuronal and synaptic loss is the most important risk factor for cognitive impairment. Inhibiting neuronal apoptosis and preventing synaptic loss are promising therapeutic approaches for Alzheimer’s disease (AD). In this study, we investigate the protective effects of Dendrobium alkaloids (DNLA), a Chinese medicinal herb extract, on β-amyloid peptide segment 25–35 (Aβ25-35)-induced neuron and synaptic loss in mice.MethodAβ25–35(10 µg) was injected into the bilateral ventricles of male mice followed by an oral administration of DNLA (40 mg/kg) for 19 days. The Morris water maze was used for evaluating the ability of spatial learning and memory function of mice. The morphological changes were examined via H&E staining and Nissl staining. TUNEL staining was used to check the neuronal apoptosis. The ultrastructure changes of neurons were observed under electron microscope. Western blot was used to evaluate the protein expression levels of ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF) in the hippocampus and cortex.ResultsDNLA significantly attenuated Aβ25–35-induced spatial learning and memory impairments in mice. DNLA prevented Aβ25–35-induced neuronal loss in the hippocampus and cortex, increased the number of Nissl bodies, improved the ultrastructural injury of neurons and increased the number of synapses in neurons. Furthermore, DNLA increased the protein expression of neurotrophic factors BDNF, CNTF and GDNF in the hippocampus and cortex.ConclusionsDNLA can prevent neuronal apoptosis and synaptic loss. This effect is mediated at least in part via increasing the expression of BDNF, GDNF and CNTF in the hippocampus and cortex; improving Aβ-induced spatial learning and memory impairment in mice.

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