当前位置： SCI文献检索 > Science Translational Medicine期刊下所有文献 > Hedgehog agonist therapy corrects structural and cognitive deficits in a Down syndrome mouse model.

Hedgehog agonist therapy corrects structural and cognitive deficits in a Down syndrome mouse model.

Abstract：

:Down syndrome (DS) is among the most frequent genetic causes of intellectual disability, and ameliorating this deficit is a major goal in support of people with trisomy 21. The Ts65Dn mouse recapitulates some major brain structural and behavioral phenotypes of DS, including reduced size and cellularity of the cerebellum and learning deficits associated with the hippocampus. We show that a single treatment of newborn mice with the Sonic hedgehog pathway agonist SAG 1.1 (SAG) results in normal cerebellar morphology in adults. Further, SAG treatment at birth rescued phenotypes associated with hippocampal deficits that occur in untreated adult Ts65Dn mice. This treatment resulted in behavioral improvements and normalized performance in the Morris water maze task for learning and memory. SAG treatment also produced physiological effects and partially rescued both N-methyl-d-aspartate (NMDA) receptor-dependent synaptic plasticity and NMDA/AMPA receptor ratio, physiological measures associated with memory. These outcomes confirm an important role for the hedgehog pathway in cerebellar development and raise the possibility for its direct influence in hippocampal function. The positive results from this approach suggest a possible direction for therapeutic intervention to improve cognitive function for this population.

journal_name

Sci Transl Med

journal_title

Science translational medicine

authors

Das I,Park JM,Shin JH,Jeon SK,Lorenzi H,Linden DJ,Worley PF,Reeves RH

doi

10.1126/scitranslmed.3005983

subject

Has Abstract

pub_date

2013-09-04 00:00:00

pages

201ra120

issue

201

eissn

1946-6234

issn

1946-6242

pii

5/201/201ra120

journal_volume

5

pub_type

杂志文章

相关文献

Science Translational Medicine文献大全
  • SIV replication in the infected rhesus macaque is limited by the size of the preexisting TH17 cell compartment.

    abstract：:The mechanisms by which some HIV-infected subjects resist disease progression, whereas others progress rapidly, are incompletely understood. Viral and host genetic factors, such as nef deletions and major histocompatibility complex alleles, explain a portion of the observed variability. However, it has been difficult ...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3003941

    authors： Hartigan-O'Connor DJ,Abel K,Van Rompay KK,Kanwar B,McCune JM

    更新日期：2012-05-30 00:00:00

  • Regulation of immune responses to protein therapeutics by transplacental induction of T cell tolerance.

    abstract：:Central tolerance plays a key role in modulating immune responses to self and exogenous antigens. The absence of self-antigen expression, as in patients with genetic deficiencies, prevents the development of antigen-specific immune tolerance. Hence, a substantial number of patients develop neutralizing antibodies to t...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aaa1957

    authors： Gupta N,Culina S,Meslier Y,Dimitrov J,Arnoult C,Delignat S,Gangadharan B,Lecerf M,Justesen S,Gouilleux-Gruart V,Salomon BL,Scott DW,Kaveri SV,Mallone R,Lacroix-Desmazes S

    更新日期：2015-02-18 00:00:00

  • Quality versus quantity: assessing individual research performance.

    abstract：:Evaluating individual research performance is a complex task that ideally examines productivity, scientific impact, and research quality--a task that metrics alone have been unable to achieve. In January 2011, the French Academy of Sciences published a report on current bibliometric (citation metric) methods for evalu...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3002249

    authors： Sahel JA

    更新日期：2011-05-25 00:00:00

  • Endomicroscope sheds light on cervical tissue.

    abstract：:A pilot study of a handheld fluorescence endomicroscope demonstrates both in vivo imaging and differentiation of normal from precancerous cervical tissue. ...

    journal_title：Science translational medicine

    pub_type： 评论,杂志文章

    doi：10.1126/scitranslmed.aal4989

    authors： Evans CL

    更新日期：2017-01-11 00:00:00

  • Osteoclast-mediated bone resorption is controlled by a compensatory network of secreted and membrane-tethered metalloproteinases.

    abstract：:Osteoclasts actively remodel both the mineral and proteinaceous components of bone during normal growth and development as well as pathologic states ranging from osteoporosis to bone metastasis. The cysteine proteinase cathepsin K confers osteoclasts with potent type I collagenolytic activity; however, cathepsin K-nul...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aaw6143

    authors： Zhu L,Tang Y,Li XY,Keller ET,Yang J,Cho JS,Feinberg TY,Weiss SJ

    更新日期：2020-02-05 00:00:00

  • Gga3 deletion and a GGA3 rare variant associated with late onset Alzheimer's disease trigger BACE1 accumulation in axonal swellings.

    abstract：:Axonal dystrophy, indicative of perturbed axonal transport, occurs early during Alzheimer's disease (AD) pathogenesis. Little is known about the mechanisms underlying this initial sign of the pathology. This study proves that Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) loss of function, due to Gga3 g...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aba1871

    authors： Lomoio S,Willen R,Kim W,Ho KZ,Robinson EK,Prokopenko D,Kennedy ME,Tanzi RE,Tesco G

    更新日期：2020-11-18 00:00:00

  • Immunoglobulin class-switched B cells form an active immune axis between CNS and periphery in multiple sclerosis.

    abstract：:In multiple sclerosis (MS), lymphocyte--in particular B cell--transit between the central nervous system (CNS) and periphery may contribute to the maintenance of active disease. Clonally related B cells exist in the cerebrospinal fluid (CSF) and peripheral blood (PB) of MS patients; however, it remains unclear which s...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3008930

    authors： Palanichamy A,Apeltsin L,Kuo TC,Sirota M,Wang S,Pitts SJ,Sundar PD,Telman D,Zhao LZ,Derstine M,Abounasr A,Hauser SL,von Büdingen HC

    更新日期：2014-08-06 00:00:00

  • Tissue-specific regulation of p53 by PKM2 is redox dependent and provides a therapeutic target for anthracycline-induced cardiotoxicity.

    abstract：:Chemotherapy-induced cardiotoxicity (CIC) is a common clinical problem that compromises effective anticancer therapies. Many chemotherapeutics (including anthracyclines, such as doxorubicin) induce the proapoptotic transcription factor p53 in the tumor and nonspecifically in the heart, promoting heart failure. Althoug...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aau8866

    authors： Saleme B,Gurtu V,Zhang Y,Kinnaird A,Boukouris AE,Gopal K,Ussher JR,Sutendra G

    更新日期：2019-02-06 00:00:00

  • Brief suppression of Abcc8 prevents autodestruction of spinal cord after trauma.

    abstract：:Spinal cord injury (SCI) is typically complicated by progressive hemorrhagic necrosis, an autodestructive process of secondary injury characterized by progressive enlargement of a hemorrhagic contusion during the first several hours after trauma. We assessed the role of Abcc8, which encodes sulfonylurea receptor 1 (SU...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3000522

    authors： Simard JM,Woo SK,Norenberg MD,Tosun C,Chen Z,Ivanova S,Tsymbalyuk O,Bryan J,Landsman D,Gerzanich V

    更新日期：2010-04-21 00:00:00

  • miRNA processing and human cancer: DICER1 cuts the mustard.

    abstract：:Numerous studies have implicated microRNAs (miRNAs) in cancer initiation and progression. In contrast, only recently has attention been focused on the pathway that generates these regulatory molecules. The identification of neoplasia-associated germline mutations in DICER1 has focused translational research on compone...

    journal_title：Science translational medicine

    pub_type： 杂志文章,评审

    doi：10.1126/scitranslmed.3002493

    authors： Bahubeshi A,Tischkowitz M,Foulkes WD

    更新日期：2011-11-30 00:00:00

  • Self-tanning cells, the new SPF.

    abstract：:A skin-penetrant small molecule activates melanin production to protect cells from cancer-inducing ultraviolet damage. ...

    journal_title：Science translational medicine

    pub_type： 评论,杂志文章

    doi：10.1126/scitranslmed.aan8202

    authors： Venere M

    更新日期：2017-07-05 00:00:00

  • Impact of guidance documents on translational large animal studies of cartilage repair.

    abstract：:Promising therapies for cartilage repair are translated through large animal models toward human application. To guide this work, regulatory agencies publish recommendations ("guidance documents") to direct pivotal large animal studies. These are meant to aid in study design, outline metrics for judging efficacy, and ...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aac7019

    authors： Pfeifer CG,Fisher MB,Carey JL,Mauck RL

    更新日期：2015-10-21 00:00:00

  • Oxidation increases mucin polymer cross-links to stiffen airway mucus gels.

    abstract：:Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we foun...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3010525

    authors： Yuan S,Hollinger M,Lachowicz-Scroggins ME,Kerr SC,Dunican EM,Daniel BM,Ghosh S,Erzurum SC,Willard B,Hazen SL,Huang X,Carrington SD,Oscarson S,Fahy JV

    更新日期：2015-02-25 00:00:00

  • Evolution-informed forecasting of seasonal influenza A (H3N2).

    abstract：:Interpandemic or seasonal influenza A, currently subtypes H3N2 and H1N1, exacts an enormous annual burden both in terms of human health and economic impact. Incidence prediction ahead of season remains a challenge largely because of the virus' antigenic evolution. We propose a forecasting approach that incorporates ev...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aan5325

    authors： Du X,King AA,Woods RJ,Pascual M

    更新日期：2017-10-25 00:00:00

  • Key elements for nourishing the translational research environment.

    abstract：:Translation in an academic environment requires a support system--people, goals, models, partnerships, and infrastructures--that will push promising basic science and technology projects forward into the clinic. ...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aaa2049

    authors： Volk HD,Stevens MM,Mooney DJ,Grainger DW,Duda GN

    更新日期：2015-04-08 00:00:00

  • Ectopic calcification in pseudoxanthoma elasticum responds to inhibition of tissue-nonspecific alkaline phosphatase.

    abstract：:Biallelic mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a disease characterized by calcification in the skin, eyes, and blood vessels. The function of ATP-binding cassette C6 (ABCC6) and the pathogenesis of PXE remain unclear. We used mouse models and patient fibroblasts to demonstrate genetic interaction a...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aal1669

    authors： Ziegler SG,Ferreira CR,MacFarlane EG,Riddle RC,Tomlinson RE,Chew EY,Martin L,Ma CT,Sergienko E,Pinkerton AB,Millán JL,Gahl WA,Dietz HC

    更新日期：2017-06-07 00:00:00

  • Therapy with CTLA4-Ig and an antiviral monoclonal antibody controls chikungunya virus arthritis.

    abstract：:In 2013, chikungunya virus (CHIKV) transmission was documented in the Western Hemisphere, and the virus has since spread throughout the Americas with more than 1.8 million people infected in more than 40 countries. CHIKV targets the joints, resulting in symmetric polyarthritis that clinically mimics rheumatoid arthrit...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aah3438

    authors： Miner JJ,Cook LE,Hong JP,Smith AM,Richner JM,Shimak RM,Young AR,Monte K,Poddar S,Crowe JE Jr,Lenschow DJ,Diamond MS

    更新日期：2017-02-01 00:00:00

  • Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells.

    abstract：:Tumor escape from immune-mediated destruction has been associated with immunosuppressive mechanisms that inhibit T cell activation. Although evidence for an active immune response, including infiltration with CD8(+) T cells, can be found in a subset of patients, those tumors are nonetheless not immunologically rejecte...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3006504

    authors： Spranger S,Spaapen RM,Zha Y,Williams J,Meng Y,Ha TT,Gajewski TF

    更新日期：2013-08-28 00:00:00

  • Long-term follow-up after gene therapy for canavan disease.

    abstract：:Canavan disease is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to loss of enzyme activity and increased concentrations of the substrate N-acetyl-aspartate (NAA) in the brain. Accumulation of NAA results in spongiform degeneration of white matter and severe impairment of p...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3003454

    authors： Leone P,Shera D,McPhee SW,Francis JS,Kolodny EH,Bilaniuk LT,Wang DJ,Assadi M,Goldfarb O,Goldman HW,Freese A,Young D,During MJ,Samulski RJ,Janson CG

    更新日期：2012-12-19 00:00:00

  • The fate and toxicity of Raman-active silica-gold nanoparticles in mice.

    abstract：:Raman spectroscopy is an optical imaging method that is based on the Raman effect, the inelastic scattering of a photon when energy is absorbed from light by a surface. Although Raman spectroscopy is widely used for chemical and molecular analysis, its clinical application has been hindered by the inherently weak natu...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3001963

    authors： Thakor AS,Luong R,Paulmurugan R,Lin FI,Kempen P,Zavaleta C,Chu P,Massoud TF,Sinclair R,Gambhir SS

    更新日期：2011-04-20 00:00:00

  • Stem cells, dot-com.

    abstract：:Direct-to-consumer (DTC) advertising of suspect goods and services has burgeoned because of the Internet. Despite very limited approval for use, DTC stem cell-marketed "treatments" have emerged for an array of conditions, creating global public health and safety risks. However, it remains unclear whether such use of s...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3004030

    authors： Liang BA,Mackey TK

    更新日期：2012-09-12 00:00:00

  • Impaired prenatal motor axon development necessitates early therapeutic intervention in severe SMA.

    abstract：:Gene replacement and pre-mRNA splicing modifier therapies represent breakthrough gene targeting treatments for the neuromuscular disease spinal muscular atrophy (SMA), but mechanisms underlying variable efficacy of treatment are incompletely understood. Our examination of severe infantile onset human SMA tissues obtai...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.abb6871

    authors： Kong L,Valdivia DO,Simon CM,Hassinan CW,Delestrée N,Ramos DM,Park JH,Pilato CM,Xu X,Crowder M,Grzyb CC,King ZA,Petrillo M,Swoboda KJ,Davis C,Lutz CM,Stephan AH,Zhao X,Weetall M,Naryshkin NA,Crawford TO,Mentis GZ

    更新日期：2021-01-27 00:00:00

  • Neutrophils cause obstruction of eyelid sebaceous glands in inflammatory eye disease in mice.

    abstract：:Meibomian glands (MGs) are sebaceous glands of the eyelid margin that secrete lipids needed to avert tear evaporation and to help maintain ocular surface homeostasis. Obstruction of MGs or other forms of MG dysfunction can promote chronic diseases of the ocular surface. Although chronic eyelid inflammation, such as al...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aas9164

    authors： Reyes NJ,Yu C,Mathew R,Kunnen CM,Kalnitsky J,Redfern RL,Leonardi A,Perez VL,MacLeod AS,Gupta PK,Saban DR

    更新日期：2018-07-25 00:00:00

  • A combination of buprenorphine and naltrexone blocks compulsive cocaine intake in rodents without producing dependence.

    abstract：:Buprenorphine, a synthetic opioid that acts at both μ and κ opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at μ opioid receptors raises its potential for creating opioid dependence in non-opioid-dependent cocaine abusers. Here, we te...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3003948

    authors： Wee S,Vendruscolo LF,Misra KK,Schlosburg JE,Koob GF

    更新日期：2012-08-08 00:00:00

  • Continuous intravesical lidocaine treatment for interstitial cystitis/bladder pain syndrome: safety and efficacy of a new drug delivery device.

    abstract：:Limited treatment options exist for patients who suffer from a painful bladder condition known as interstitial cystitis/bladder pain syndrome (IC/BPS). Whether given systemically (orally) or by short-duration (1 to 2 hours) exposure via intravesical instillation, therapeutic agents have exhibited poor efficacy because...

    journal_title：Science translational medicine

    pub_type： 杂志文章,随机对照试验

    doi：10.1126/scitranslmed.3003804

    authors： Nickel JC,Jain P,Shore N,Anderson J,Giesing D,Lee H,Kim G,Daniel K,White S,Larrivee-Elkins C,Lekstrom-Himes J,Cima M

    更新日期：2012-07-18 00:00:00

  • Photoactivation of endogenous latent transforming growth factor-β1 directs dental stem cell differentiation for regeneration.

    abstract：:Rapid advancements in the field of stem cell biology have led to many current efforts to exploit stem cells as therapeutic agents in regenerative medicine. However, current ex vivo cell manipulations common to most regenerative approaches create a variety of technical and regulatory hurdles to their clinical translati...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3008234

    authors： Arany PR,Cho A,Hunt TD,Sidhu G,Shin K,Hahm E,Huang GX,Weaver J,Chen AC,Padwa BL,Hamblin MR,Barcellos-Hoff MH,Kulkarni AB,J Mooney D

    更新日期：2014-05-28 00:00:00

  • Beyond disease, how biomedical engineering can improve global health.

    abstract：:Biomedical engineering tools can be harnessed to address some of the world's most challenging nondisease-focused problems. ...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3009067

    authors： LeDuc P,Agaba M,Cheng CM,Gracio J,Guzman A,Middelberg A

    更新日期：2014-12-10 00:00:00

  • Immune-mediated pathology in Duchenne muscular dystrophy.

    abstract：:Immunological and inflammatory processes downstream of dystrophin deficiency as well as metabolic abnormalities, defective autophagy, and loss of regenerative capacity all contribute to muscle pathology in Duchenne muscular dystrophy (DMD). These downstream cascades offer potential avenues for pharmacological interven...

    journal_title：Science translational medicine

    pub_type： 杂志文章,评审

    doi：10.1126/scitranslmed.aaa7322

    authors： Rosenberg AS,Puig M,Nagaraju K,Hoffman EP,Villalta SA,Rao VA,Wakefield LM,Woodcock J

    更新日期：2015-08-05 00:00:00

  • Hypercapnia increases airway smooth muscle contractility via caspase-7-mediated miR-133a-RhoA signaling.

    abstract：:The elevation of carbon dioxide (CO2) in tissues and the bloodstream (hypercapnia) occurs in patients with severe lung diseases, including chronic obstructive pulmonary disease (COPD). Whereas hypercapnia has been recognized as a marker of COPD severity, a role for hypercapnia in disease pathogenesis remains unclear. ...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.aat1662

    authors： Shigemura M,Lecuona E,Angulo M,Homma T,Rodríguez DA,Gonzalez-Gonzalez FJ,Welch LC,Amarelle L,Kim SJ,Kaminski N,Budinger GRS,Solway J,Sznajder JI

    更新日期：2018-09-05 00:00:00

  • Carbamylation of serum albumin as a risk factor for mortality in patients with kidney failure.

    abstract：:Urea, the toxic end product of protein catabolism, is elevated in end-stage renal disease (ESRD), although it is unclear whether or how it contributes to disease. Urea can promote the carbamylation of proteins on multiple lysine side chains, including human albumin, which has a predominant carbamylation site on Lys(54...

    journal_title：Science translational medicine

    pub_type： 杂志文章

    doi：10.1126/scitranslmed.3005218

    authors： Berg AH,Drechsler C,Wenger J,Buccafusca R,Hod T,Kalim S,Ramma W,Parikh SM,Steen H,Friedman DJ,Danziger J,Wanner C,Thadhani R,Karumanchi SA

    更新日期：2013-03-06 00:00:00