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 Reelin Improves Cognition and Extends the Lifespan of Mutant Ndel1 Mice with Postnatal CA1 Hippocampus Deterioration

2020 ◽  
Vol 30 (9) ◽  
pp. 4964-4978 ◽  
Author(s):  
Ivana Kiroski ◽  
Yulan Jiang ◽  
Cezar Gavrilovici ◽  
Fan Gao ◽  
Sukyoung Lee ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Pyramidal Neurons ◽  
Neurological Diseases ◽  
Memory Function ◽  
Neuronal Cell ◽  
Adult Brain ◽  
Conditional Knockout ◽  
Spatial Learning And Memory ◽  
Ca1 Pyramidal Neurons

Abstract The glycoprotein Reelin maintains neuronal positioning and regulates neuronal plasticity in the adult brain. Reelin deficiency has been associated with neurological diseases. We recently showed that Reelin is depleted in mice with a targeted disruption of the Ndel1 gene in forebrain postnatal excitatory neurons (Ndel1 conditional knockout (CKO)). Ndel1 CKO mice exhibit fragmented microtubules in CA1 pyramidal neurons, profound deterioration of the CA1 hippocampus and a shortened lifespan (~10 weeks). Here we report that Ndel1 CKO mice (of both sexes) experience spatial learning and memory deficits that are associated with deregulation of neuronal cell adhesion, plasticity and neurotransmission genes, as assessed by genome-wide transcriptome analysis of the hippocampus. Importantly, a single injection of Reelin protein in the hippocampus of Ndel1 CKO mice improves spatial learning and memory function and this is correlated with reduced intrinsic hyperexcitability of CA1 pyramidal neurons, and normalized gene deregulation in the hippocampus. Strikingly, when treated with Reelin, Ndel1 CKO animals that die from an epileptic phenotype, live twice as long as nontreated, or vehicle-treated CKO animals. Thus, Reelin confers striking beneficial effects in the CA1 hippocampus, and at both behavioral and organismal levels.

Spatial learning and memory function-related gene expression in the hippocampus of mouse exposed to nanoparticle-rich diesel exhaust

2008 ◽  
Vol 29 (6) ◽  
pp. 940-947 ◽  
Author(s):  
Tin-Tin Win-Shwe ◽  
Shoji Yamamoto ◽  
Yuji Fujitani ◽  
Seishiro Hirano ◽  
Hidekazu Fujimaki
Keyword(s):  
Gene Expression ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Diesel Exhaust ◽  
Memory Function ◽  
Spatial Learning And Memory ◽  
Related Gene

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.

Maternal and postweaning high-fat diets disturb hippocampal gene expression, learning, and memory function

2014 ◽  
Vol 306 (8) ◽  
pp. R527-R537 ◽  
Author(s):  
Kathleen C. Page ◽  
Elizabeth K. Jones ◽  
Endla K. Anday
Keyword(s):  
Gene Expression ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Memory Function ◽  
Saturated Fat ◽  
Spatial Learning And Memory ◽  
Adult Males ◽  
High Fat ◽  
High Fat Diets ◽  
Fat Diets

We tested the hypothesis that excess saturated fat consumption during pregnancy, lactation, and/or postweaning alters the expression of genes mediating hippocampal synaptic efficacy and impairs spatial learning and memory in adulthood. Dams were fed control chow or a diet high in saturated fat before mating, during pregnancy, and into lactation. Offspring were weaned to either standard chow or a diet high in saturated fat. The Morris Water Maze was used to evaluate spatial learning and memory. Open field testing was used to evaluate motor activity. Hippocampal gene expression in adult males was measured using RT-PCR and ELISA. Offspring from high fat-fed dams took longer, swam farther, and faster to try and find the hidden platform during the 5-day learning period. Control offspring consuming standard chow spent the most time in memory quadrant during the probe test. Offspring from high fat-fed dams consuming excess saturated fat spent the least. The levels of mRNA and protein for brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein were significantly decreased by maternal diet effects. Nerve growth factor mRNA and protein levels were significantly reduced in response to both maternal and postweaning high-fat diets. Expression levels for the N-methyl-d-aspartate receptor (NMDA) receptor subunit NR2B as well as synaptophysin were significantly decreased in response to both maternal and postweaning diets. Synaptotagmin was significantly increased in offspring from high fat-fed dams. These data support the hypothesis that exposure to excess saturated fat during hippocampal development is associated with complex patterns of gene expression and deficits in learning and memory.

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 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.

scholarly journals Germacrone alleviates neurological deficits following traumatic brain injury by modulating neuroinflammation and oxidative stress

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sujing Zhuang ◽  
Baogui Liu ◽  
Shifeng Guo ◽  
Yanzhong Xue ◽  
Lin Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Neuronal Apoptosis ◽  
Spatial Learning And Memory ◽  
Dependent Manner ◽  
Dose Dependent ◽  
And Oxidative Stress

Abstract Background Germacrone (GM) is a terpenoid compound which is reported to have anti-inflammatory and anti-oxidative effects. However, its role in treating traumatic brain injury (TBI) remains largely unknown. Methods Male C57BL/6 mice were divided into the following groups: control group, TBI group [controlled cortical impact (CCI) model], CCI + 5 mg/kg GM group, CCI + 10 mg/kg GM group and CCI + 20 mg/kg GM group. GM was administered via intraperitoneal injection. The neurological functions (including motor coordination, spatial learning and memory abilities) and brain edema were measured. Nissl staining was used to detect the neuronal apoptosis. Colorimetric assays and enzyme linked immunosorbent assay (ELISA) kits were used to determine the expression levels of oxidative stress markers including myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of inflammatory markers, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Additionally, protein levels of Nrf2 and p-p65 were detected by Western blot assay. Results GM significantly ameliorated motor dysfunction, spatial learning and memory deficits of the mice induced by TBI and it also reduced neuronal apoptosis and microglial activation in a dose-dependent manner. Besides, GM treatment reduced neuroinflammation and oxidative stress compared to those in the CCI group in a dose-dependent manner. Furthermore, GM up-regulated the expression of antioxidant protein Nrf2 and inhibited the expression of inflammatory response protein p-p65. Conclusions GM is a promising drug to improve the functional recovery after TBI via repressing neuroinflammation and oxidative stress.

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