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.

FTY720 (Fingolimod) Attenuates Beta-amyloid Peptide (Aβ42)-Induced Impairment of Spatial Learning and Memory in Rats

2013 ◽  
Vol 50 (3) ◽  
pp. 524-532 ◽  
Author(s):  
Masoumeh Asle-Rousta ◽  
Zeynab Kolahdooz ◽  
Shahrbanoo Oryan ◽  
Abolhassan Ahmadiani ◽  
Leila Dargahi
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Beta Amyloid ◽  
Amyloid Peptide ◽  
Spatial Learning And Memory ◽  
Beta Amyloid Peptide

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 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 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 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 Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity- and neurotransmission-related proteins in young recipients

Microbiome ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Alfonsina D’Amato ◽  
Lorenzo Di Cesare Mannelli ◽  
Elena Lucarini ◽  
Angela L. Man ◽  
Gwenaelle Le Gall ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Young Adult ◽  
Protein Expression ◽  
Learning And Memory ◽  
Intestinal Microbiota ◽  
Spatial Learning ◽  
Cognitive Functions ◽  
Spatial Learning And Memory ◽  
Faecal Microbiota ◽  
Aged Donor

Abstract Background The gut-brain axis and the intestinal microbiota are emerging as key players in health and disease. Shifts in intestinal microbiota composition affect a variety of systems; however, evidence of their direct impact on cognitive functions is still lacking. We tested whether faecal microbiota transplant (FMT) from aged donor mice into young adult recipients altered the hippocampus, an area of the central nervous system (CNS) known to be affected by the ageing process and related functions. Results Young adult mice were transplanted with the microbiota from either aged or age-matched donor mice. Following transplantation, characterization of the microbiotas and metabolomics profiles along with a battery of cognitive and behavioural tests were performed. Label-free quantitative proteomics was employed to monitor protein expression in the hippocampus of the recipients. We report that FMT from aged donors led to impaired spatial learning and memory in young adult recipients, whereas anxiety, explorative behaviour and locomotor activity remained unaffected. This was paralleled by altered expression of proteins involved in synaptic plasticity and neurotransmission in the hippocampus. Also, a strong reduction of bacteria associated with short-chain fatty acids (SCFAs) production (Lachnospiraceae, Faecalibaculum, and Ruminococcaceae) and disorders of the CNS (Prevotellaceae and Ruminococcaceae) was observed. Finally, the detrimental effect of FMT from aged donors on the CNS was confirmed by the observation that microglia cells of the hippocampus fimbria, acquired an ageing-like phenotype; on the contrary, gut permeability and levels of systemic and local (hippocampus) cytokines were not affected. Conclusion These results demonstrate that age-associated shifts of the microbiota have an impact on protein expression and key functions of the CNS. Furthermore, these results highlight the paramount importance of the gut-brain axis in ageing and provide a strong rationale to devise therapies aiming to restore a young-like microbiota to improve cognitive functions and the declining quality of life in the elderly.

scholarly journals Synaptic Loss in a Mouse Model of Euthyroid Hashimoto’s Thyroiditis: Possible Involvement of the Microglia

2021 ◽  
Author(s):  
Fen Wang ◽  
Yao-Jun Cai ◽  
Xiao Ma ◽  
Nan Wang ◽  
Zhang-Bi Wu ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Morris Water Maze ◽  
Spatial Learning ◽  
Hashimoto’S Thyroiditis ◽  
Water Maze ◽  
Hashimoto's Thyroiditis ◽  
Spatial Learning And Memory ◽  
Synaptic Loss ◽  
Activated Microglia ◽  
Euthyroid State

Abstract Background: Hashimoto’s thyroiditis (HT) is an autoimmune illness that renders individuals vulnerable to neuropsychopathology even in the euthyroid state, the mechanisms involved remain unclear. We hypothesized that activated microglia might disrupt synapses, resulting in cognitive disturbance in the context of euthyroid HT, and designed the present study to test this hypothesis. Methods: Experimental HT model was induced by immunizing NOD mice with thyroglobulin and adjuvant twice. Morris Water Maze was measured to determine mice spatial learning and memory. The synaptic parameters such as the synaptic density, synaptic ultrastructure and synaptic-markers (SYN and PSD95) as well as the interactions of microglia with synapses were also determined. Results: HT mice had poorer performance in Morris Water Maze than controls. Concurrently, HT resulted in a significant reduction in synapse density and ultrastructure damage, along with decreased synaptic puncta visualized by immunostaining with synaptophysin and PSD-95. In parallel, frontal activated microglia in euthyroid HT mice showed increased engulfment of PSD95 and EM revealed that the synaptic structures were visible within the microglia. These functional alterations in microglia corresponded to structural increases in their attachment to neuronal perikarya and a reduction in presynaptic terminals covering the neurons.Conclusion: Our results provide initial evidence that HT can induce synaptic loss in the euthyroid state with deficits might be attributable to activated microglia, which may underlie the deleterious effects of HT on spatial learning and memory.

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