当前位置： SCI文献检索 > NATURE期刊下所有文献 > Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function.

Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function.

Abstract：

:Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.

journal_name

Nature

journal_title

Nature

authors

Won H,Lee HR,Gee HY,Mah W,Kim JI,Lee J,Ha S,Chung C,Jung ES,Cho YS,Park SG,Lee JS,Lee K,Kim D,Bae YC,Kaang BK,Lee MG,Kim E

doi

10.1038/nature11208

subject

Has Abstract

pub_date

2012-06-13 00:00:00

pages

261-5

issue

7402

eissn

0028-0836

issn

1476-4687

pii

nature11208

journal_volume

486

pub_type

杂志文章

相关文献

NATURE文献大全
  • Genome sequence of Yersinia pestis, the causative agent of plague.

    abstract：:The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/35097083

    authors： Parkhill J,Wren BW,Thomson NR,Titball RW,Holden MT,Prentice MB,Sebaihia M,James KD,Churcher C,Mungall KL,Baker S,Basham D,Bentley SD,Brooks K,Cerdeño-Tárraga AM,Chillingworth T,Cronin A,Davies RM,Davis P,Dougan G,

    更新日期：2001-10-04 00:00:00

  • Gut intraepithelial T cells calibrate metabolism and accelerate cardiovascular disease.

    abstract：:The biochemical response to food intake must be precisely regulated. Because ingested sugars and fats can feed into many anabolic and catabolic pathways1, how our bodies handle nutrients depends on strategically positioned metabolic sensors that link the intrinsic nutritional value of a meal with intermediary metaboli...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/s41586-018-0849-9

    authors： He S,Kahles F,Rattik S,Nairz M,McAlpine CS,Anzai A,Selgrade D,Fenn AM,Chan CT,Mindur JE,Valet C,Poller WC,Halle L,Rotllan N,Iwamoto Y,Wojtkiewicz GR,Weissleder R,Libby P,Fernández-Hernando C,Drucker DJ,Nahrendorf

    更新日期：2019-02-01 00:00:00

  • A test of reciprocal X-Y interactions as a cause of hybrid sterility in Drosophila.

    abstract：:Elucidation of the nature of the gene interactions that underly the sterility of interspecific hybrids is important in evolutionary biology. The interactions between the heterospecific X and Y (or Z and W) chromosomes are often used as an explanation for two reasons. First, the fertility of the hybrids of the heteroga...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/358751a0

    authors： Johnson NA,Perez DE,Cabot EL,Hollocher H,Wu CI

    更新日期：1992-08-27 00:00:00

  • Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP.

    abstract：:The innate immune defence of multicellular organisms against microbial pathogens requires cellular collaboration. Information exchange allowing immune cells to collaborate is generally attributed to soluble protein factors secreted by pathogen-sensing cells. Cytokines, such as type I interferons (IFNs), serve to alert...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature12640

    authors： Ablasser A,Schmid-Burgk JL,Hemmerling I,Horvath GL,Schmidt T,Latz E,Hornung V

    更新日期：2013-11-28 00:00:00

  • Trace element signature of subduction-zone fluids, melts and supercritical liquids at 120-180 km depth.

    abstract：:Fluids and melts liberated from subducting oceanic crust recycle lithophile elements back into the mantle wedge, facilitate melting and ultimately lead to prolific subduction-zone arc volcanism. The nature and composition of the mobile phases generated in the subducting slab at high pressures have, however, remained l...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature03971

    authors： Kessel R,Schmidt MW,Ulmer P,Pettke T

    更新日期：2005-09-29 00:00:00

  • Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis.

    abstract：:During endocytosis, clathrin and the clathrin adaptor protein AP-2, assisted by a variety of accessory factors, help to generate an invaginated bud at the cell membrane. One of these factors is Eps15, a clathrin-coat-associated protein that binds the alpha-adaptin subunit of AP-2. Here we investigate the function of E...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/29555

    authors： Chen H,Fre S,Slepnev VI,Capua MR,Takei K,Butler MH,Di Fiore PP,De Camilli P

    更新日期：1998-08-20 00:00:00

  • Crystal structure of opsin in its G-protein-interacting conformation.

    abstract：:Opsin, the ligand-free form of the G-protein-coupled receptor rhodopsin, at low pH adopts a conformationally distinct, active G-protein-binding state known as Ops*. A synthetic peptide derived from the main binding site of the heterotrimeric G protein-the carboxy terminus of the alpha-subunit (GalphaCT)-stabilizes Ops...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature07330

    authors： Scheerer P,Park JH,Hildebrand PW,Kim YJ,Krauss N,Choe HW,Hofmann KP,Ernst OP

    更新日期：2008-09-25 00:00:00

  • Massive star formation within the Leo 'primordial' ring.

    abstract：:Few intergalactic, plausibly primordial clouds of neutral atomic hydrogen (H(i)) have been found in the local Universe, suggesting that such structures have either dispersed, become ionized or produced a stellar population on gigayear timescales. The Leo ring, a massive (M(H(i)) approximately 1.8 x 10(9)M[symbol: see ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature07780

    authors： Thilker DA,Donovan J,Schiminovich D,Bianchi L,Boissier S,de Paz AG,Madore BF,Martin DC,Seibert M

    更新日期：2009-02-19 00:00:00

  • Detection of metastable electronic states by Penning trap mass spectrometry.

    abstract：:State-of-the-art optical clocks1 achieve precisions of 10-18 or better using ensembles of atoms in optical lattices2,3 or individual ions in radio-frequency traps4,5. Promising candidates for use in atomic clocks are highly charged ions6 (HCIs) and nuclear transitions7, which are largely insensitive to external pertur...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/s41586-020-2221-0

    authors： Schüssler RX,Bekker H,Braß M,Cakir H,Crespo López-Urrutia JR,Door M,Filianin P,Harman Z,Haverkort MW,Huang WJ,Indelicato P,Keitel CH,König CM,Kromer K,Müller M,Novikov YN,Rischka A,Schweiger C,Sturm S,Ulmer S,Elis

    更新日期：2020-05-01 00:00:00

  • Exciton-polariton topological insulator.

    abstract：:Topological insulators-materials that are insulating in the bulk but allow electrons to flow on their surface-are striking examples of materials in which topological invariants are manifested in robustness against perturbations such as defects and disorder1. Their most prominent feature is the emergence of edge states...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/s41586-018-0601-5

    authors： Klembt S,Harder TH,Egorov OA,Winkler K,Ge R,Bandres MA,Emmerling M,Worschech L,Liew TCH,Segev M,Schneider C,Höfling S

    更新日期：2018-10-01 00:00:00

  • Loss of plant species after chronic low-level nitrogen deposition to prairie grasslands.

    abstract：:Rates of atmospheric deposition of biologically active nitrogen (N) are two to seven times the pre-industrial rates in many developed nations because of combustion of fossil fuels and agricultural fertilization. They are expected to increase similarly over the next 50 years in industrializing nations of Asia and South...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature06503

    authors： Clark CM,Tilman D

    更新日期：2008-02-07 00:00:00

  • Retinal pigmented epithelial cells induced to transdifferentiate to neurons by laminin.

    abstract：:Although the regeneration of nervous tissue in the vertebrate is very limited, there are a few remarkable examples of this process. Understanding the factors that regulate CNS regeneration in those areas of the nervous system where it occurs, will doubtless provide generally applicable, essential information about the...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/330068a0

    authors： Reh TA,Nagy T,Gretton H

    更新日期：1987-11-05 00:00:00

  • A glimmer of light for neuropsychiatric disorders.

    abstract：:Understanding the pathogenesis of neuropsychiatric disorders is a substantial challenge for neurobiologists. It has long been hoped that identifying alleles that confer increased risk of such disorders would provide clues for neurobiological investigation. But this quest has been stymied by a lack of validated biologi...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature07454

    authors： Hyman SE

    更新日期：2008-10-16 00:00:00

  • The zootype and the phylotypic stage.

    abstract：:What is it that defines an animal? The definition provided here, made on the basis of developmental biology, suggests methods for resolving phylogenetic problems. ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/361490a0

    authors： Slack JM,Holland PW,Graham CF

    更新日期：1993-02-11 00:00:00

  • How B and T cells talk to each other.

    abstract：:The B cells of the immune system, which secrete antibodies against foreign antigens, are fully specific and effective only after maturation in lymph nodes and other lymphoid tissues. Immunocompetent T cells play a crucial part in this process, but the molecular details of the way in which the two cell types interact h...

    journal_title：Nature

    pub_type： 杂志文章,评审

    doi：10.1038/367425a0

    authors： Clark EA,Ledbetter JA

    更新日期：1994-02-03 00:00:00

  • Discovery central.

    abstract：: ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/d41586-018-07209-z

    authors： Jia H

    更新日期：2018-11-01 00:00:00

  • Regulated degradation of a class V myosin receptor directs movement of the yeast vacuole.

    abstract：:Normal cellular function requires that organelles be positioned in specific locations. The direction in which molecular motors move organelles is based in part on the polarity of microtubules and actin filaments. However, this alone does not determine the intracellular destination of organelles. For example, the yeast...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature01453

    authors： Tang F,Kauffman EJ,Novak JL,Nau JJ,Catlett NL,Weisman LS

    更新日期：2003-03-06 00:00:00

  • Chemical and behavioural characterization of the rabbit mammary pheromone.

    abstract：:Mammals owe part of their evolutionary success to the harmonious exchanges of information, energy and immunity between females and their offspring. This functional reciprocity is vital for the survival and normal development of infants, and for the inclusive fitness of parents. It is best seen in the intense exchanges...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature01739

    authors： Schaal B,Coureaud G,Langlois D,Giniès C,Sémon E,Perrier G

    更新日期：2003-07-03 00:00:00

  • Corrigendum: Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance.

    abstract：:This corrects the article DOI: 10.1038/nature22794. ...

    journal_title：Nature

    pub_type： 杂志文章,已发布勘误

    doi：10.1038/nature25162

    authors： Shaffer SM,Dunagin MC,Torborg SR,Torre EA,Emert B,Krepler C,Beqiri M,Sproesser K,Brafford PA,Xiao M,Eggan E,Anastopoulos IN,Vargas-Garcia CA,Singh A,Nathanson KL,Herlyn M,Raj A

    更新日期：2018-03-08 00:00:00

  • Dichloroacetate prevents restenosis in preclinical animal models of vessel injury.

    abstract：:Despite the introduction of antiproliferative drug-eluting stents, coronary heart disease remains the leading cause of death in the United States. In-stent restenosis and bypass graft failure are characterized by excessive smooth muscle cell (SMC) proliferation and concomitant myointima formation with luminal oblitera...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature13232

    authors： Deuse T,Hua X,Wang D,Maegdefessel L,Heeren J,Scheja L,Bolaños JP,Rakovic A,Spin JM,Stubbendorff M,Ikeno F,Länger F,Zeller T,Schulte-Uentrop L,Stoehr A,Itagaki R,Haddad F,Eschenhagen T,Blankenberg S,Kiefmann R,Reic

    更新日期：2014-05-29 00:00:00

  • An N-terminal peptide from p60src can direct myristylation and plasma membrane localization when fused to heterologous proteins.

    abstract：:The src gene product, p60src, of Rous sarcoma virus (RSV) is a tyrosine-specific protein kinase which is associated with the plasma membrane of infected cells. Myristic acid is bound in an amide linkage to glycine 2 of p60src. Of the N-terminal 30 kilodaltons of p60src, only amino acids 1-14 are required for myristyla...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/314374a0

    authors： Pellman D,Garber EA,Cross FR,Hanafusa H

    更新日期：1985-03-28 00:00:00

  • Mapping of the class II region of the human major histocompatibility complex by pulsed-field gel electrophoresis.

    abstract：:The class II region of the human major histocompatibility complex (MHC) encodes a polymorphic set of cell surface glycoproteins involved in the regulation of the immune response. Each glycoprotein is a heterodimer composed of a alpha-chain of relative molecular mass (Mr) 34,000 (34 K) and a beta-chain of Mr = 28K. The...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/323453a0

    authors： Hardy DA,Bell JI,Long EO,Lindsten T,McDevitt HO

    更新日期：1986-10-02 00:00:00

  • The sodium channel and intracellular H+ blockage in squid axons.

    abstract：:Sodium channels in plasma membranes can be blocked by a large variety of toxins and local anaesthetics. This property, however, is not confined to relatively large molecules. For instance, extracellularly applied small ions like hydrogen may also prevent the passive transport of permeant cations across open Na+ channe...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/287062a0

    authors： Wanke E,Carbone E,Testa PL

    更新日期：1980-09-04 00:00:00

  • Three-dimensional structure of the 67K N-terminal fragment of E. coli DNA topoisomerase I.

    abstract：:The three-dimensional structure of the 67K amino-terminal fragment of Escherichia coli DNA topoisomerase I has been determined to 2.2 A resolution. The polypeptide folds in an unusual way to give four distinct domains enclosing a hole large enough to accommodate a double-stranded DNA. The active-site tyrosyl residue, ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/367138a0

    authors： Lima CD,Wang JC,Mondragón A

    更新日期：1994-01-13 00:00:00

  • Role of spectral detail in sound-source localization.

    abstract：:Sounds heard over headphones are typically perceived inside the head (internalized), unlike real sound sources which are perceived outside the head (externalized). If the acoustical waveforms from a real sound source are reproduced precisely using headphones, auditory images are appropriately externalized and localize...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/25526

    authors： Kulkarni A,Colburn HS

    更新日期：1998-12-24 00:00:00

  • Hot streaks in artistic, cultural, and scientific careers.

    abstract：:The hot streak-loosely defined as 'winning begets more winnings'-highlights a specific period during which an individual's performance is substantially better than his or her typical performance. Although hot streaks have been widely debated in sports1,2, gambling3-5 and financial markets6,7 over the past several deca...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/s41586-018-0315-8

    authors： Liu L,Wang Y,Sinatra R,Giles CL,Song C,Wang D

    更新日期：2018-07-01 00:00:00

  • Glutamate induces de novo growth of functional spines in developing cortex.

    abstract：:Mature cortical pyramidal neurons receive excitatory inputs onto small protrusions emanating from their dendrites called spines. Spines undergo activity-dependent remodelling, stabilization and pruning during development, and similar structural changes can be triggered by learning and changes in sensory experiences. H...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature09986

    authors： Kwon HB,Sabatini BL

    更新日期：2011-06-02 00:00:00

  • Sequencing the nuclear genome of the extinct woolly mammoth.

    abstract：:In 1994, two independent groups extracted DNA from several Pleistocene epoch mammoths and noted differences among individual specimens. Subsequently, DNA sequences have been published for a number of extinct species. However, such ancient DNA is often fragmented and damaged, and studies to date have typically focused ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature07446

    authors： Miller W,Drautz DI,Ratan A,Pusey B,Qi J,Lesk AM,Tomsho LP,Packard MD,Zhao F,Sher A,Tikhonov A,Raney B,Patterson N,Lindblad-Toh K,Lander ES,Knight JR,Irzyk GP,Fredrikson KM,Harkins TT,Sheridan S,Pringle T,Schuste

    更新日期：2008-11-20 00:00:00

  • H-2 restriction of contact inhibition of epithelial cells.

    abstract：:Medawar has suggested that the major histocompatibility gene complex (MHC) might be involved in the contact inhibition of movement shown by fibroblasts and epithelia. Contact inhibition of movement is that reaction of cells which stops the movement of one cell over another and thus leads to monolayering and other feat...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/281222a0

    authors： Curtis AS,Rooney P

    更新日期：1979-09-20 00:00:00

  • Active transport of Ca2+ by an artificial photosynthetic membrane.

    abstract：:Transport of calcium ions across membranes and against a thermodynamic gradient is essential to many biological processes, including muscle contraction, the citric acid cycle, glycogen metabolism, release of neurotransmitters, vision, biological signal transduction and immune response. Synthetic systems that transport...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature01209

    authors： Bennett IM,Farfano HM,Bogani F,Primak A,Liddell PA,Otero L,Sereno L,Silber JJ,Moore AL,Moore TA,Gust D

    更新日期：2002-11-28 00:00:00