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https://www.readbyqxmd.com/read/29452226/quantitative-proteomic-analysis-reveals-synaptic-dysfunction-in-the-amygdala-of-rats-susceptible-to-chronic-mild-stress
#1
Mi Zhou, Zhao Liu, Jia Yu, Shuiming Li, Min Tang, Li Zeng, Haiyang Wang, Hong Xie, Li Peng, Haojun Huang, Chanjuan Zhou, Peng Xie, Jian Zhou
The amygdala plays a key role in the pathophysiology of depression, but the molecular mechanisms underlying amygdalar hyperactivity in depression remain unclear. In this study, we used a chronic mild stress (CMS) protocol to separate susceptible and insusceptible rat subgroups. Proteomes in the amygdalae were analyzed differentially across subgroups based on labeling with isobaric tags for relative and absolute quantitation (iTRAQ) combined with mass spectrometry. Of 2,562 quantified proteins, 102 were differentially expressed...
February 13, 2018: Neuroscience
https://www.readbyqxmd.com/read/29439327/stabilized-low-n-amyloid-%C3%AE-oligomers-induce-robust-novel-object-recognition-deficits-associated-with-inflammatory-synaptic-and-gabaergic-dysfunction-in-the-rat
#2
William Watremez, Joshua Jackson, Bushra Almari, Samantha L McLean, Ben Grayson, Joanna C Neill, Nicolas Fischer, Ahmad Allouche, Violette Koziel, Thierry Pillot, Michael K Harte
BACKGROUND: With current treatments for Alzheimer's disease (AD) only providing temporary symptomatic benefits, disease modifying drugs are urgently required. This approach relies on improved understanding of the early pathophysiology of AD. A new hypothesis has emerged, in which early memory loss is considered a synapse failure caused by soluble amyloid-β oligomers (Aβo). These small soluble Aβo, which precede the formation of larger fibrillar assemblies, may be the main cause of early AD pathologies...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29429936/%C3%AE-actinin-anchors-psd-95-at-postsynaptic-sites
#3
Lucas Matt, Karam Kim, Anne E Hergarden, Tommaso Patriarchi, Zulfiqar A Malik, Deborah K Park, Dhrubajyoti Chowdhury, Olivia R Buonarati, Peter B Henderson, Çiğdem Gökçek Saraç, Yonghong Zhang, Durga Mohapatra, Mary C Horne, James B Ames, Johannes W Hell
Despite the central role PSD-95 plays in anchoring postsynaptic AMPARs, how PSD-95 itself is tethered to postsynaptic sites is not well understood. Here we show that the F-actin binding protein α-actinin binds to the very N terminus of PSD-95. Knockdown (KD) of α-actinin phenocopies KD of PSD-95. Mutating lysine at position 10 or lysine at position 11 of PSD-95 to glutamate, or glutamate at position 53 or glutamate and aspartate at positions 213 and 217 of α-actinin, respectively, to lysine impairs, in parallel, PSD-95 binding to α-actinin and postsynaptic localization of PSD-95 and AMPARs...
February 7, 2018: Neuron
https://www.readbyqxmd.com/read/29427282/neonatal-exposure-to-low-dose-1-2-sevoflurane-increases-rats-hippocampal-neurogenesis-and-synaptic-plasticity-in-later-life
#4
Xi Chen, Xue Zhou, Lu Yang, Xu Miao, Di-Han Lu, Xiao-Yu Yang, Zhi-Bin Zhou, Wen-Bin Kang, Ke-Yu Chen, Li-Hua Zhou, Xia Feng
The increasing usage of general anesthetics on young children and infants has drawn extensive attention to the effects of these drugs on cognitive function later in life. Recent animal studies have revealed improvement in hippocampus-dependent performance after lower concentrations of sevoflurane exposure. However, the long-term effects of low-dose sevoflurane on the developing brain remain elusive. On postnatal day (P) 7, rats were treated with 1.2% sevoflurane (1.2% sevo group), 2.4% sevoflurane (2.4% sevo group), and air control (C group) for 6 h...
February 9, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29385704/discovery-of-cryoprotective-activity-in-human-genome-derived-intrinsically-disordered-proteins
#5
Naoki Matsuo, Natsuko Goda, Kana Shimizu, Satoshi Fukuchi, Motonori Ota, Hidekazu Hiroaki
Intrinsically disordered proteins (IDPs) are an emerging phenomenon. They may have a high degree of flexibility in their polypeptide chains, which lack a stable 3D structure. Although several biological functions of IDPs have been proposed, their general function is not known. The only finding related to their function is the genetically conserved YSK₂ motif present in plant dehydrins. These proteins were shown to be IDPs with the YSK₂ motif serving as a core region for the dehydrins' cryoprotective activity...
January 30, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29384407/effect-of-aucubin-on-neural-precursor-cell-survival-during-neuronal-differentiation
#6
Miyeoun Song, Maeum Han, Yunhee Kim Kwon
Aucubin (ACB) is an iridoid glycoside with various biological activities. Previously it is reported that ACB reduces cell survival and proliferation in many human tumors, whereas it facilitates cell survival and neuroprotection in damaged neuronal cells and disease models. However, its effects on cell survival in the non-proliferating or differentiated neurons are not known. We examined whether ACB facilitated cell survival in differentiating neural precursor cells, HiB5, compared with the proliferating HiB5 cells at various concentrations...
January 31, 2018: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29369181/revealing-the-action-mechanisms-of-dexamethasone-on-the-birth-weight-of-infant-using-rna-sequencing-data-of-trophoblast-cells
#7
Hongkai Shang, Liping Sun, Thorsten Braun, Qi Si, Jinyi Tong
Dexamethasone (DEX) could induce low birth weight of infant, and low birth weight has close associations with glucocorticoid levels, insulin resistance, hypertension, and metabolic syndrome in adulthood. This study was designed to reveal the action mechanisms of DEX on the birth weight of infant.Using quantitative real-time polymerase chain reaction (qRT-PCR), trophoblast cells of human placenta were identified and the optimum treatment time of DEX were determined. Trophoblast cells were treated by DEX (DEX group) or ethanol (control group) (each group had 3 samples), and then were performed with RNA-sequencing...
January 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29367010/chronic-minocycline-treatment-improves-hippocampal-neuronal-structure-nmda-receptor-function-and-memory-processing-in-fmr1-knockout-mice
#8
S Y Yau, Luis Bettio, M Vetrici, A Truesdell, C Chiu, J Chiu, E Truesdell, B R Christie
Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability, and is the leading known single-gene cause of autism spectrum disorder. FXS patients display varied behavioural deficits that include mild to severe cognitive impairments in addition to mood disorders. Currently there is no cure for this condition, however minocycline is becoming commonly prescribed as a treatment for FXS patients. Minocycline has been reported to alleviate social behavioural deficits, and improve verbal functioning in patients with FXS; however, its mode of action is not well understood...
January 20, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29339557/chronic-dietary-creatine-enhances-hippocampal-dependent-spatial-memory-bioenergetics-and-levels-of-plasticity-related-proteins-associated-with-nf-%C3%AE%C2%BAb
#9
Wanda M Snow, Chris Cadonic, Claudia Cortes-Perez, Subir K Roy Chowdhury, Jelena Djordjevic, Ella Thomson, Michael J Bernstein, Miyoung Suh, Paul Fernyhough, Benedict C Albensi
The brain has a high demand for energy, of which creatine (Cr) is an important regulator. Studies document neurocognitive benefits of oral Cr in mammals, yet little is known regarding their physiological basis. This study investigated the effects of Cr supplementation (3%, w/w) on hippocampal function in male C57BL/6 mice, including spatial learning and memory in the Morris water maze and oxygen consumption rates from isolated mitochondria in real time. Levels of transcription factors and related proteins (CREB, Egr1, and IκB to indicate NF-κB activity), proteins implicated in cognition (CaMKII, PSD-95, and Egr2), and mitochondrial proteins (electron transport chain Complex I, mitochondrial fission protein Drp1) were probed with Western blotting...
February 2018: Learning & Memory
https://www.readbyqxmd.com/read/29335844/the-adiponectin-homolog-osmotin-enhances-neurite-outgrowth-and-synaptic-complexity-via-adipor1-ngr1-signaling-in-alzheimer-s-disease
#10
Gwangho Yoon, Shahid Ali Shah, Tahir Ali, Myeong Ok Kim
Alzheimer's disease is a major neurodegenerative disease characterized by memory loss and cognitive deficits. Recently, we reported that osmotin, which is a homolog of adiponectin, improved long-term potentiation and cognitive functions in Alzheimer's disease mice. Several lines of evidence have suggested that Nogo-A and the Nogo-66 receptor 1 (NgR1), which form a complex that inhibits long-term potentiation and cognitive function, might be associated with the adiponectin receptor 1 (AdipoR1), which is a receptor for osmotin...
January 15, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29321508/thrombospondin-1-secreted-by-human-umbilical-cord-blood-derived-mesenchymal-stem-cells-rescues-neurons-from-synaptic-dysfunction-in-alzheimer-s-disease-model
#11
Dong Hyun Kim, Hoon Lim, Dahm Lee, Soo Jin Choi, Wonil Oh, Yoon Sun Yang, Jeong Su Oh, Hyun Ho Hwang, Hong Bae Jeon
Alzheimer's disease (AD) is an incurable neurodegenerative disease characterised clinically by learning and memory impairments. Amyloid beta (Aβ) peptide-induced synaptic dysfunction is a pathological process associated with early-stage AD. Here, we show that paracrine action of human umbilical cord blood-derived-mesenchymal stem cells (hUCB-MSCs) protects the hippocampus from synaptic-density loss in in vitro and in vivo AD models. To identify paracrine factors underlying this rescue effect, we analysed hUCB-MSCs' secretome co-cultured with Aβ42-treated mouse hippocampal neurons...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29284046/irsp53-accumulates-at-the-postsynaptic-density-under-excitatory-conditions
#12
Ayse Dosemeci, Amelia Burch, Hannah Loo, Dana Toy, Jung-Hwa Tao-Cheng
IRSp53 (BAIAP2) is an abundant protein at the postsynaptic density (PSD) that binds to major PSD scaffolds, PSD-95 and Shanks, as well as to F-actin. The distribution of IRSp53 at the PSD in cultured hippocampal neurons was examined under basal and excitatory conditions by immuno-electron microscopy. Under basal conditions, label for IRSp53 is concentrated at the PSD. Upon depolarization by application of a medium containing 90 mM K+, the intensity of IRSp53 label at the PSD increased by 36±7%. Application of NMDA (50 μM) yielded 53±1% increase in the intensity of IRSp53 label at the PSD compared to controls treated with APV, an NMDA antagonist...
2017: PloS One
https://www.readbyqxmd.com/read/29281827/synaptic-targeting-and-function-of-sapaps-mediated-by-phosphorylation-dependent-binding-to-psd-95-maguks
#13
Jinwei Zhu, Qingqing Zhou, Yuan Shang, Hao Li, Mengjuan Peng, Xiao Ke, Zhuangfeng Weng, Rongguang Zhang, Xuhui Huang, Shawn S C Li, Guoping Feng, Youming Lu, Mingjie Zhang
The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating the formation and plasticity of the post-synaptic densities (PSDs). We previously demonstrated that the exquisitely specific SAPAP/Shank interaction is critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here, we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in complex with a phosphor-SAPAP repeat peptide, together with biochemical studies, reveals the molecular mechanism underlying the phosphorylation-dependent PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95 mutation found in patients with intellectual disabilities...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29277119/brain-derived-neurotropic-factor-bdnf-heterozygous-mice-are-more-susceptible-to-synaptic-protein-loss-in-cerebral-cortex-during-high-fat-diet
#14
İsmail Abidin, Selcen Aydin-Abidin, Akin Bodur, İmran İnce, Ahmet Alver
In this study we aimed to investigate whether reduced BDNF levels aggravate the susceptibility of the brain to hazardous effects of high fat diet. For this purpose, we fed BDNF heterozygous mice and wild type littermates with normal and high fat diet for 16 weeks. Concentrations of two synaptic proteins (SNAP-25 and PSD-95) and oxidative stress parameters (MDA, SOD, CAT) were evaluated in the cortex after diet period. Interestingly, body weights of BDNF heterozygous groups fed with control diet were higher than their littermates and heterozygous mice fed with HFD were the heaviest in all experimental groups...
December 25, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29259324/revisiting-medial-preoptic-area-plasticity-induced-in-male-mice-by-sexual-experience
#15
Arnaud Jean, Pauline Bonnet, Philippe Liere, Sakina Mhaouty-Kodja, Helene Hardin-Pouzet
Sexual experience in male rodents, induced by a first exposure to a receptive female, improves efficiency of following copulations. In mice, the mechanisms supporting this improvement are poorly understood. We characterized molecular modifications of the mouse hypothalamic medial preoptic area (mPOA), the main integrative structure for male sexual behaviour, after a single mating event. This paradigm induced long-lasting behavioural improvements and mPOA morphological changes, evidenced by dendritic spine maturation and an increase in the acetylated and tri-methylated forms of histone H3...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29250591/shank-proteins-differentially-regulate-synaptic-transmission
#16
Rebecca Shi, Patrick Redman, Dipanwita Ghose, Yan Liu, Xiaobai Ren, Lei J Ding, Mingna Liu, Kendrick J Jones, Weifeng Xu
Shank proteins, one of the principal scaffolds in the postsynaptic density (PSD) of the glutamatergic synapses, have been associated with autism spectrum disorders and neuropsychiatric diseases. However, it is not known whether different Shank family proteins have distinct functions in regulating synaptic transmission, and how they differ from other scaffold proteins in this aspect. Here, we investigate the role of Shanks in regulating glutamatergic synaptic transmission at rat hippocampal SC-CA1 synapses, using lentivirus-mediated knockdown and molecular replacement combined with dual whole-cell patch clamp in hippocampal slice culture...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29248482/targeted-inhibition-of-rage-reduces-amyloid-%C3%AE-influx-across-the-blood-brain-barrier-and-improves-cognitive-deficits-in-db-db-mice
#17
Hao Wang, Fang Chen, Yi-Feng Du, Yan Long, Miranda N Reed, Mei Hu, Vishnu Suppiramaniam, Hao Hong, Su-Su Tang
AIMS: To investigate restorative effects of the receptor for advanced glycation end products (RAGE)-specific inhibitor FPS-ZM1 on abnormal amyloid (Aβ) influx across the blood brain-barrier (BBB) and cognitive deficits in db/db mice. METHODS: Aβ influx across the BBB was determined by intra-arterial infusion of 125I-Aβ1-40. Receptor for advanced glycation end products (RAGE), Aβ, NF-κB p65, caspase-3, Bax, Bcl-2, PSD-95 and synaptophysin were assayed by Western blot, immunohistochemistry or RT-PCR...
December 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29247260/adolescent-cocaine-exposure-induces-prolonged-synaptic-modifications-in-medial-prefrontal-cortex-of-adult-rats
#18
Wei Zhu, Xuhui Ge, Peng Gao, Min Li, Yun Guan, Xiaowei Guan
Substance used during adolescent period increases the risk of psychiatric disorders in later life, but the underlying neural mechanisms remain unclear. We hypothesize that synaptic remodeling and changes of homeostasis in the medial prefrontal cortex (mPFC) following adolescent cocaine exposure may last for a long time, and these modifications may contribute to behavioral deficiencies in adulthood. To address this hypothesis, rats were exposed to cocaine hydrochloride from postnatal day 28 (P28) to P42. When reared to adulthood, rats were subjected to behavioral tests...
December 15, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29237242/enhanced-cognition-and-dysregulated-hippocampal-synaptic-physiology-in-mice-with-a-heterozygous-deletion-of-psd-95
#19
Alexa E Horner, Catherine L McLaughlin, Nurudeen O Afinowi, Timothy J Bussey, Lisa M Saksida, Noboru H Komiyama, Seth G N Grant, Maksym V Kopanitsa
PSD-95 is one of the most abundant proteins of the postsynaptic density of excitatory synapses. It functions as the backbone of protein supercomplexes that mediate signalling between membrane glutamate receptors and intracellular pathways. Homozygous deletion of the Dlg4 gene encoding PSD-95 was previously found to cause a profound impairment in operant and Pavlovian conditioning in Dlg4-/- mice studied in touchscreen chambers that precluded evaluation of PSD-95's role in shaping more subtle forms of learning and memory...
December 13, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29234273/indirubin-derivative-7-bromoindirubin-3-oxime-7bio-attenuates-a%C3%AE-oligomer-induced-cognitive-impairments-in-mice
#20
Liping Chen, Chunhui Huang, Jieyi Shentu, Minjun Wang, Sicheng Yan, Fei Zhou, Zaijun Zhang, Chuang Wang, Yifan Han, Qinwen Wang, Wei Cui
Indirubins are natural occurring alkaloids extracted from indigo dye-containing plants. Indirubins could inhibit various kinases, and might be used to treat chronic myelocytic leukemia, cancer and neurodegenerative disorders. 7-bromoindirubin-3-oxime (7Bio), an indirubin derivative derived from indirubin-3-oxime, possesses inhibitory effects against cyclin-dependent kinase-5 (CDK5) and glycogen synthase kinase-3β (GSK3β), two pharmacological targets of Alzheimer's disease (AD). In this study, we have discovered that 2...
2017: Frontiers in Molecular Neuroscience
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