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https://www.readbyqxmd.com/read/29237242/enhanced-cognition-and-dysregulated-hippocampal-synaptic-physiology-in-mice-with-a-heterozygous-deletion-of-psd-95
#1
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
#2
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
https://www.readbyqxmd.com/read/29229294/impact-of-dha-intake-in-a-mouse-model-of-synucleinopathy
#3
Katherine Coulombe, Olivier Kerdiles, Cyntia Tremblay, Vincent Emond, Manon Lebel, Anne-Sophie Boulianne, Mélanie Plourde, Francesca Cicchetti, Frédéric Calon
Polyunsaturated fatty acids omega-3 (n-3 PUFA), such as docosahexaenoic acid (DHA), have been shown to prevent, and partially reverse, neurotoxin-induced nigrostriatal denervation in animal models of Parkinson's disease (PD). However, the accumulation of α-synuclein (αSyn) in cerebral tissues is equally important to the pathophysiology. To determine whether DHA intake improves various aspects related to synucleinopathy, ninety male mice overexpressing human αSyn under the Thy-1 promoter (Thy1-αSyn) were fed one of three diets (specially formulated control, low n-3 PUFA or high DHA) and compared to non-transgenic C57/BL6 littermate mice exposed to a control diet...
December 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29225110/assessment-of-the-cerebellar-neurotoxic-effects-of-nicotine-in-prenatal-alcohol-exposure-in-rats
#4
Dwipayan Bhattacharya, Mohammed Majrashi, Sindhu Ramesh, Manoj Govindarajulu, Jenna Bloemer, Ayaka Fujihashi, Bailee-Ryan Crump, Harrison Hightower, Subhrajit Bhattacharya, Timothy Moore, Vishnu Suppiramaniam, Muralikrishnan Dhanasekaran
The adverse effects of prenatal nicotine and alcohol exposure on human reproductive outcomes are a major scientific and public health concern. In the United States, substantial percentage of women (20-25%) of childbearing age currently smoke cigarettes and consume alcohol, and only a small percentage of these individuals quit after learning of their pregnancy. However, there are very few scientific reports on the effect of nicotine in prenatal alcohol exposure on the cerebellum of the offspring. Therefore, this study was conducted to investigate the cerebellar neurotoxic effects of nicotine in a rodent model of Fetal Alcohol Spectrum Disorder (FASD)...
December 7, 2017: Life Sciences
https://www.readbyqxmd.com/read/29214369/ginkgolide-k-promotes-the-clearance-of-a53t-mutation-alpha-synuclein-in-sh-sy5y-cells
#5
Wenbo Yu, Sheng Chen, Liang Cao, Jie Tang, Wei Xiao, Baoguo Xiao
Alpha-synuclein (α-syn) is associated to Parkinson's disease (PD). The aggregated form of α-syn has potential neurotoxicity. Thus, the clearance of α-syn aggregation is a plausible strategy to delay disease progression of PD. In our study, we found that the treatment of Ginkgolide B (GB) and Ginkgolide K (GK) reduced cell death, and enhanced cell proliferation in SH-SY5Y cells, which overexpressed A53T mutant α-syn. Surprisingly, GK, but not GB, promoted the clearance of A53T α-syn, which can be abolished by autophagy inhibitor 3-methyladenine, indicating that GK-induced autophagy intervened in the clearance of A53T α-syn...
December 6, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/29180720/snx27-links-dgk%C3%AE-to-the-control-of-transcriptional-and-metabolic-programs-in-t-lymphocytes
#6
M Tello-Lafoz, C Rodríguez-Rodríguez, G Kinna, L S Loo, W Hong, B M Collins, R D Teasdale, I Mérida
Sorting nexin 27 (SNX27) recycles PSD-95, Dlg1, ZO-1 (PDZ) domain-interacting membrane proteins and is essential to sustain adequate brain functions. Here we define a fundamental SNX27 function in T lymphocytes controlling antigen-induced transcriptional activation and metabolic reprogramming. SNX27 limits the activation of diacylglycerol (DAG)-based signals through its high affinity PDZ-interacting cargo DAG kinase ζ (DGKζ). SNX27 silencing in human T cells enhanced T cell receptor (TCR)-stimulated activator protein 1 (AP-1)- and nuclear factor κB (NF-κB)-mediated transcription...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29180226/microwave-radiation-leading-to-shrinkage-of-dendritic-spines-in-hippocampal-neurons-mediated-by-snk-spar-pathway
#7
Wei-Jia Zhi, Rui-Yun Peng, Hai-Juan Li, Yong Zou, Bin-Wei Yao, Chang-Zhen Wang, Zong-Huan Liu, Xiao-Hui Gao, Xin-Ping Xu, Ji Dong, Zhao Li, Hong-Mei Zhou, Li-Feng Wang, Xiang-Jun Hu
The popularization of microwave raised concerns about its influence on health including cognitive function which is associated greatly with dendritic spines plasticity. SNK-SPAR is a molecular pathway for neuronal homeostatic plasticity during chronically elevated activity. In this study, Wistar rats were exposed to microwaves (30 mW/cm2 for 6 min, 3 times/week for 6 weeks). Spatial learning and memory function, distribution of dendritic spines, ultrastructure of the neurons and their dendritic spines in hippocampus as well as the related critical molecules of SNK-SPAR pathway in rats hippocampus were examined at different time points after microwave exposure...
November 24, 2017: Brain Research
https://www.readbyqxmd.com/read/29169997/psd95-a-synaptic-protein-implicated-in-schizophrenia-or-autism
#8
REVIEW
Austin A Coley, Wen-Jun Gao
The molecular components of the postsynaptic density (PSD) in excitatory synapses of the brain are currently being investigated as one of the major etiologies of neurodevelopmental disorders such as schizophrenia (SCZ) and autism. Postsynaptic density protein-95 (PSD-95) is a major regulator of synaptic maturation by interacting, stabilizing and trafficking N-methyl-d-aspartic acid receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isox-azoleproprionic acid receptors (AMPARs) to the postsynaptic membrane...
November 20, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29168728/interference-of-htlv-1-tax-protein-with-cell-polarity-regulators-defining-the-subcellular-localization-of-the-tax-dlg1-interaction
#9
Federico Marziali, Marina Bugnon Valdano, Clarisse Brunet Avalos, Lucía Moriena, Ana Laura Cavatorta, Daniela Gardiol
Human T cell leukemia virus (HTLV)-1 Tax (Tax) protein is very important in viral replication and cell transformation. Tax localizes in the nucleus and cytoplasm in association with organelles. Some activities of Tax depend on interactions with PDZ (PSD-95/Discs Large/Z0-1) domain-containing proteins such as Discs large protein 1 (DLG1) which is involved in cell polarity and proliferation. The DLG1 interaction results in a cytoplasmic co-localization pattern resembling vesicular aggregates, the nature of which is still unknown...
November 23, 2017: Viruses
https://www.readbyqxmd.com/read/29167635/physical-exercise-promotes-novel-object-recognition-memory-in-spontaneously-hypertensive-rats-after-ischemic-stroke-by-promoting-neural-plasticity-in-the-entorhinal-cortex
#10
Xiaona Pan, Ting Jiang, Liying Zhang, Haiqing Zheng, Jing Luo, Xiquan Hu
Cerebral ischemia leads to memory impairment, and several studies have indicated that physical exercise (PE) has memory-improving effects after ischemia. This study was designed to further explore the specific role of PE in novel object recognition (NOR) memory after stroke and the exact cortical regions in which memory is restored by PE. Spontaneously hypertensive rats (SHR) were subjected to transient middle cerebral artery occlusion (tMCAO) or sham surgery, followed by 26 days of PE starting on day 3 post-tMCAO...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29166700/dlp1-dependent-mitochondrial-fragmentation-and-redistribution-mediate-prion-associated-mitochondrial-dysfunction-and-neuronal-death
#11
Chaosi Li, Di Wang, Wei Wu, Wei Yang, Syed Zahid Ali Shah, Ying Zhao, Yuhan Duan, Lu Wang, Xiangmei Zhou, Deming Zhao, Lifeng Yang
Mitochondrial malfunction is a universal and critical step in the pathogenesis of many neurodegenerative diseases including prion diseases. Dynamin-like protein 1 (DLP1) is one of the key regulators of mitochondrial fission. In this study, we investigated the role of DLP1 in mitochondrial fragmentation and dysfunction in neurons using in vitro and in vivo prion disease models. Mitochondria became fragmented and redistributed from axons to soma, correlated with increased mitochondrial DLP1 expression in murine primary neurons (N2a cells) treated with the prion peptide PrP(106-126) in vitro as well as in prion strain-infected hamster brain in vivo...
November 22, 2017: Aging Cell
https://www.readbyqxmd.com/read/29149481/neuroprotective-effects-of-melatonin-on-amphetamine-induced-dopaminergic-fiber-degeneration-in-the-hippocampus-of-postnatal-rats
#12
Tanawan Leeboonngam, Ratchadaporn Pramong, Kwankanit Sae-Ung, Piyarat Govitrapong, Pansiri Phansuwan-Pujito
Chronic amphetamine (AMPH) abuse leads to damage of the hippocampus, the brain area associated with learning and memory process. Previous results have shown that AMPH-induced dopamine neurotransmitter release, reactive oxygen species formation and degenerative protein aggregation lead to neuronal death. Melatonin, a powerful antioxidant, plays a role as a neuroprotective agent. The objective of this study was to investigate whether the protective effect of melatonin on AMPH-induced hippocampal damage in the postnatal rat acts through the dopaminergic pathway...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29146293/andrographolide-a-promising-therapeutic-agent-negatively-regulates-glial-cell-derived-neurodegeneration-of-prefrontal-cortex-hippocampus-and-working-memory-impairment
#13
Sudeshna Das, K P Mishra, Lilly Ganju, S B Singh
Over activation of glial cell derived innate immune factors induces neuro-inflammation that results in neurodegenerative disease, like working memory impairment. In this study, we have investigated the role of andrographolide, a major constituent of Andrographis paniculata plant, in reduction of reactive glial cell derived working memory impairment. Real time PCR, Western bloting, flow cytometric and immunofluorescence studies demonstrated that andrographolide inhibited lipopolysaccharide (LPS)-induced overexpression of HMGB1, TLR4, NFκB, COX-2, iNOS, and release of inflammatory mediators in primary mix glial culture, adult mice prefrontal cortex and hippocampus region...
November 8, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29142062/the-serine-protease-inhibitor-neuroserpin-is-required-for-normal-synaptic-plasticity-and-regulates-learning-and-social-behavior
#14
Rebecca Reumann, Ricardo Vierk, Lepu Zhou, Frederice Gries, Vanessa Kraus, Julia Mienert, Eva Romswinkel, Fabio Morellini, Isidre Ferrer, Chiara Nicolini, Margaret Fahnestock, Gabriele Rune, Markus Glatzel, Giovanna Galliciotti
The serine protease inhibitor neuroserpin regulates the activity of tissue-type plasminogen activator (tPA) in the nervous system. Neuroserpin expression is particularly prominent at late stages of neuronal development in most regions of the central nervous system (CNS), whereas it is restricted to regions related to learning and memory in the adult brain. The physiological expression pattern of neuroserpin, its high degree of colocalization with tPA within the CNS, together with its dysregulation in neuropsychiatric disorders, suggest a role in formation and refinement of synapses...
December 2017: Learning & Memory
https://www.readbyqxmd.com/read/29138001/pdz-ligand-binding-induced-conformational-coupling-of-the-pdz-sh3-gk-tandems-in-psd-95-family-maguks
#15
Menglong Zeng, Fei Ye, Jia Xu, Mingjie Zhang
DLG MAGUKs are abundantly expressed in glutamatergic synapses, crucial for synaptic transmission and plasticity by anchoring various postsynaptic components including glutamate receptors, downstream scaffold proteins and signaling enzymes. Different DLG members have shared structures and functions, but also contain unique features. How DLG family proteins function individually and cooperatively are largely unknown. Here, we report that PSD-95 PDZ3 directly couples with SH3-GK tandem in a PDZ ligand binding-dependent manner, and the coupling can promote PSD-95 dimerization and multimerization...
November 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29136779/juglanin-ameliorates-lps-induced-neuroinflammation-in-animal-models-of-parkinson-s-disease-and-cell-culture-via-inactivating-tlr4-nf-%C3%AE%C2%BAb-pathway
#16
Fang-Xue Zhang, Ren-Shi Xu
Parkinson's disease (PD) is a common neuro-degenerative disorder, and novel therapeutic targets are required for the treatment of PD. Juglanin is a natural compound extracted from the crude Polygonum aviculare, exhibiting anti-inflammatory, anti-oxidant and anti-cancer activities. In our study, PD in mice was induced by systemic LPS treatment as evidenced by enhanced α-synuclein and reduced tyrosine hydroxylase (TH), which were reversed by juglanin treatment. Moreover, juglanin administration attenuated LPS-caused behavioral and memory impairments and reduced LPS-induced enhancement of neuro-degenerative markers, including amyloid β (Aβ) and p-Tau...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29134655/protein-components-of-postsynaptic-density-lattice-a-backbone-structure-for-type-i-excitatory-synapses
#17
Tatsuo Suzuki, Kiyokazu Kametani, Weiheng Guo, Weidong Li
It is essential to study the molecular architecture of postsynaptic density (PSD) to understand the molecular mechanism underlying the dynamic nature of PSD, one of the bases of synaptic plasticity. A well-known model for the architecture of PSD of type I excitatory synapses basically comprises of several scaffolding proteins (scaffold protein model). On the contrary, "PSD lattice" observed through electron microscopy has been considered a basic backbone of type I PSDs. However, major constituents of the PSD lattice and the relationship between the PSD lattice and the scaffold protein model, are unknown...
November 14, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29121065/proteomic-analysis-reveals-novel-ligands-and-substrates-for-lnx1-e3-ubiquitin-ligase
#18
Joan A Lenihan, Orthis Saha, Paul W Young
Ligand of Numb protein X1 (LNX1) is an E3 ubiquitin ligase that contains a catalytic RING (Really Interesting New Gene) domain and four PDZ (PSD-95, DlgA, ZO-1) domains. LNX1 can ubiquitinate Numb, as well as a number of other ligands. However, the physiological relevance of these interactions in vivo remain unclear. To gain functional insights into the LNX family, we have characterised the LNX1 interactome using affinity purification and mass spectrometry. This approach identified a large number of novel LNX1-interacting proteins, as well as confirming known interactions with NUMB and ERC2...
2017: PloS One
https://www.readbyqxmd.com/read/29118000/ca-2-calmodulin-binding-to-psd-95-mediates-homeostatic-synaptic-scaling-down
#19
Dhrubajyoti Chowdhury, Matthew Turner, Tommaso Patriarchi, Anne C Hergarden, David Anderson, Yonghong Zhang, Junqing Sun, Chao-Yin Chen, James B Ames, Johannes W Hell
Postsynaptic density protein-95 (PSD-95) localizes AMPA-type glutamate receptors (AMPARs) to postsynaptic sites of glutamatergic synapses. Its postsynaptic displacement is necessary for loss of AMPARs during homeostatic scaling down of synapses. Here, we demonstrate that upon Ca(2+) influx, Ca(2+)/calmodulin (Ca(2+)/CaM) binding to the N-terminus of PSD-95 mediates postsynaptic loss of PSD-95 and AMPARs during homeostatic scaling down. Our NMR structural analysis identified E17 within the PSD-95 N-terminus as important for binding to Ca(2+)/CaM by interacting with R126 on CaM...
November 8, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29112734/memantine-prevents-acute-radiation-induced-toxicities-at-hippocampal-excitatory-synapses
#20
Joseph G Duman, Jeffrey Dinh, Wei Zhou, Henry Cham, Vasilis C Mavratsas, Matea Paveškovic, Shalaka Mulherkar, Susan L McGovern, Kimberley F Tolias, David R Grosshans
Background: Memantine has shown clinical utility in preventing radiation-induced cognitive impairment, but the mechanisms underlying its protective effects remain unknown. We hypothesized that abnormal glutamate signaling causes radiation-induced abnormalities in neuronal structure and that memantine prevents synaptic toxicity. Methods: Hippocampal cultures expressing eGFP were irradiated or sham-treated and their dendritic spine morphology assessed at acute (minutes) and later (days) times using high-resolution confocal microscopy...
November 2, 2017: Neuro-oncology
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