Abstract:
:Cannabis abuse during adolescence confers an increased risk for developing later in life cognitive deficits reminiscent of those observed in schizophrenia, suggesting common pathological mechanisms that remain poorly characterized. In line with previous findings that revealed a role of 5-HT6 receptor-operated mTOR activation in cognitive deficits of rodent developmental models of schizophrenia, we show that chronic administration of ∆9-tetrahydrocannabinol (THC) to mice during adolescence induces a long-lasting activation of mTOR in prefrontal cortex (PFC), alterations of excitatory/inhibitory balance, intrinsic properties of layer V pyramidal neurons, and long-term depression, as well as cognitive deficits in adulthood. All are prevented by administrating a 5-HT6 receptor antagonist or rapamycin, during adolescence. In contrast, they are still present 2 weeks after the same treatments delivered at the adult stage. Collectively, these findings suggest a role of 5-HT6 receptor-operated mTOR signaling in abnormalities of cortical network wiring elicited by THC at a critical period of PFC maturation and highlight the potential of 5-HT6 receptor antagonists as early therapy to prevent cognitive symptom onset in adolescent cannabis abusers.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Berthoux C,Hamieh AM,Rogliardo A,Doucet EL,Coudert C,Ango F,Grychowska K,Chaumont-Dubel S,Zajdel P,Maldonado R,Bockaert J,Marin P,Bécamel Cdoi
10.15252/emmm.201910605subject
Has Abstractpub_date
2020-05-08 00:00:00pages
e10605issue
5eissn
1757-4676issn
1757-4684journal_volume
12pub_type
杂志文章abstract::A homozygous mutation in the gene for sigma 1 receptor (Sig1R) is a cause of inherited juvenile amyotrophic lateral sclerosis (ALS16). Sig1R localizes to the mitochondria-associated membrane (MAM), which is an interface of mitochondria and endoplasmic reticulum. However, the role of the MAM in ALS is not fully elucida...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201606403
更新日期:2016-12-01 00:00:00
abstract::Trop-2, a cell surface glycoprotein, contains both extracellular epidermal growth factor-like and thyroglobulin type-1 repeat domains. Low TROP2 expression was observed in lung adenocarcinoma tissues as compared with their normal counterparts. The lack of expression could be due to either the loss of heterozygosity (L...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201200222
更新日期:2012-06-01 00:00:00
abstract::The Plasmodium-infected hepatocyte has been considered necessary to prime the immune responses leading to sterile protection after vaccination with attenuated sporozoites. However, it has recently been demonstrated that priming also occurs in the skin. We wished to establish if sterile protection could be obtained in ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201201677
更新日期:2013-02-01 00:00:00
abstract::Vascular endothelial growth factor C (VEGF-C) binding to its tyrosine kinase receptor VEGFR-3 drives lymphatic vessel growth during development and in pathological processes. Although the VEGF-C/VEGFR-3 pathway provides a target for treatment of cancer and lymphedema, the physiological functions of VEGF-C in adult vas...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201505731
更新日期:2015-11-01 00:00:00
abstract::Endothelial dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) and that exogenously administered microRNA may be of therapeutic benefit. Lower levels of miR-483 were found in serum from patients with idiopathic pulmonary arterial hypertension (IPAH), particularly those with...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201911303
更新日期:2020-05-08 00:00:00
abstract::Familial Mediterranean fever (FMF) is the most frequent hereditary systemic autoinflammatory syndrome. FMF is usually caused by biallelic mutations in the MEFV gene, encoding Pyrin. Conclusive genetic evidence lacks for about 30% of patients diagnosed with clinical FMF. Pyrin is an inflammasome sensor maintained inact...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201910547
更新日期:2019-11-07 00:00:00
abstract::Resistance to tamoxifen is a clinically major challenge in breast cancer treatment. Although downregulation of estrogen receptor-alpha (ERα) is the dominant mechanism of tamoxifen resistance, the reason for ERα decrease during tamoxifen therapy remains elusive. Herein, we reported that Spalt-like transcription factor ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201910638
更新日期:2019-12-01 00:00:00
abstract::Progression to severe disease is a difficult problem in treating coronavirus disease 2019 (COVID-19). The purpose of this study is to explore changes in markers of severe disease in COVID-19 patients. Sixty-nine severe COVID-19 patients were included. Patients with severe disease showed significant lymphocytopenia. El...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012421
更新日期:2020-07-07 00:00:00
abstract::Mitochondrial (mt) diseases are multisystem disorders due to mutations in nuclear or mtDNA genes. Among the latter, more than 50% are located in transfer RNA (tRNA) genes and are responsible for a wide range of syndromes, for which no effective treatment is available at present. We show that three human mt aminoacyl-t...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201303198
更新日期:2014-02-01 00:00:00
abstract::Telomerase is expressed in the neonatal brain, in distinct regions of adult brain, and was shown to protect developing neurons from apoptosis. Telomerase reactivation by gene manipulation reverses neurodegeneration in aged telomerase-deficient mice. Hence, we and others hypothesized that increasing telomerase expressi...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201200212
更新日期:2012-04-01 00:00:00
abstract::The current management of colorectal cancer (CRC) would greatly benefit from non-invasive prognostic biomarkers indicative of clinicopathological tumor characteristics. Here, we employed targeted proteomic profiling of 80 glycoprotein biomarker candidates across plasma samples of a well-annotated patient cohort with c...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404874
更新日期:2015-09-01 00:00:00
abstract::Gene targeting constitutes a new step in the development of gene therapy for inherited diseases. Although previous studies have shown the feasibility of editing fibroblasts from Fanconi anemia (FA) patients, here we aimed at conducting therapeutic gene editing in clinically relevant cells, such as hematopoietic stem c...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201707540
更新日期:2017-11-01 00:00:00
abstract::Mutations in POLG disrupt mtDNA replication and cause devastating diseases often with neurological phenotypes. Defining disease mechanisms has been hampered by limited access to human tissues, particularly neurons. Using patient cells carrying POLG mutations, we generated iPSCs and then neural stem cells. These neural...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012146
更新日期:2020-10-07 00:00:00
abstract::Various disorders including pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI), which are caused by inactivating mutations in ABCC6 and ENPP1, respectively, present with extensive tissue calcification due to reduced plasma pyrophosphate (PPi). However, it has always been assumed th...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201707532
更新日期:2017-11-01 00:00:00
abstract::Synaptic inhibition is essential for shaping the dynamics of neuronal networks, and aberrant inhibition plays an important role in neurological disorders. Gephyrin is a central player at inhibitory postsynapses, directly binds and organizes GABAA and glycine receptors (GABAARs and GlyRs), and is thereby indispensable ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201505323
更新日期:2015-12-01 00:00:00
abstract::The nucleoside adenosine is a potent regulator of vascular homeostasis, but it remains unclear how expression or function of the adenosine-metabolizing enzyme adenosine kinase (ADK) and the intracellular adenosine levels influence angiogenesis. We show here that hypoxia lowered the expression of ADK and increased the ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201607066
更新日期:2017-09-01 00:00:00
abstract::Genomic data sharing is becoming more important as scientists join forces across borders in biomedical research for the benefit of patients and society. The EU's General Data Protection Regulation (GDPR) helps simplify sharing of such data at the European and international level. However, initial optimism has dried up...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201911421
更新日期:2020-03-06 00:00:00
abstract::Both the incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally; in the industrialized world up to 0.5% of the population are affected and around 4.2 million individuals suffer from IBD in Europe and North America combined. Successful engraftment in experimental colitis models suggests tha...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.15252/emmm.201607260
更新日期:2017-05-01 00:00:00
abstract::Formation of pathogenic antibodies is a major problem in replacement therapies for inherited protein deficiencies. For example, antibodies to coagulation factors ('inhibitors') seriously complicate treatment of haemophilia. While immune tolerance induction (ITI) protocols have been developed, inhibitors against factor...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201302859
更新日期:2013-11-01 00:00:00
abstract::The lack of actionable mutations in patients with non-small cell lung cancer (NSCLC) presents a significant hurdle in the design of targeted therapies for this disease. Here, we identify somatically mutated ABL1 as a genetic dependency that is required to maintain NSCLC cell survival. We demonstrate that NSCLC cells w...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201505456
更新日期:2016-02-01 00:00:00
abstract::Patients affected by mitochondrial OXPHOS disorders are still faced with a grim lack of therapeutic options. In this Closeup, Carlos Moraes revisits the recent data by Giovanni Manfredi on PKA's functions in the mitochondria and now its modulation can improve respiration and ATP production in COX-defective cells. ...
journal_title:EMBO molecular medicine
pub_type: 评论,杂志文章
doi:10.1002/emmm.200900049
更新日期:2009-11-01 00:00:00
abstract::Secreted Semaphorin 3E (Sema3E) promotes cancer cell invasiveness and metastatic spreading. The pro-metastatic activity of Sema3E is due to its proteolytic fragment p61, capable of transactivating the oncogenic tyrosine kinase ErbB2 that associates with the Sema3E receptor PlexinD1 in cancer cells. Here, we show that ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201100205
更新日期:2012-03-01 00:00:00
abstract::Autologous haematopoietic stem cell transplantation is highly efficient for the treatment of systemic autoimmune diseases, but its consequences for the immune system remain poorly understood. Here, we describe an optimized RNA-based technology for unbiased amplification of T cell receptor beta-chain libraries and use ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201100129
更新日期:2011-04-01 00:00:00
abstract::The tumor suppressor gene TP53 is the most frequently mutated gene in cancer. The compound APR-246 (PRIMA-1Met/Eprenetapopt) is converted to methylene quinuclidinone (MQ) that targets mutant p53 protein and perturbs cellular antioxidant balance. APR-246 is currently tested in a phase III clinical trial in myelodysplas...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201910852
更新日期:2020-12-14 00:00:00
abstract::The insulin/insulin-like growth factor-1 signalling (IIS) pathway regulates cellular and organismal metabolism and controls the rate of aging. Gain-of-function mutations in p110α, the principal mammalian IIS-responsive isoform of PI 3-kinase (PI3K), promote cancer. In contrast, loss-of-function mutations in p110α impa...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201201953
更新日期:2013-04-01 00:00:00
abstract::Activation of non-shivering thermogenesis (NST) in brown adipose tissue (BAT) has been proposed as an anti-obesity treatment. Moreover, cold-induced glucose uptake could normalize blood glucose levels in insulin-resistant patients. It is therefore important to identify novel regulators of NST and cold-induced glucose ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201505610
更新日期:2016-03-01 00:00:00
abstract::Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance, other factors such as c-Myc and the E2F family also play a role in later stage disease. HES6 is a transcription co-factor associated with stem cell characteristics in neur...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201303581
更新日期:2014-05-01 00:00:00
abstract::Heart failure entails the inability of the heart to pump blood to vital organs. One of the main risk factors for heart failure is the development of pathological hypertrophy. In this issue of EMBO Molecular Medicine, Li and coworkers show that NCoR1, a co-repressor of transcription factors, inhibits the transcriptiona...
journal_title:EMBO molecular medicine
pub_type: 评论,杂志文章
doi:10.15252/emmm.201911297
更新日期:2019-11-07 00:00:00
abstract::Translational read-through-inducing drugs (TRIDs) promote read-through of nonsense mutations, placing them in the spotlight of current gene-based therapeutic research. Here, we compare for the first time the relative efficacies of new-generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal to...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201201438
更新日期:2012-11-01 00:00:00
abstract::Brain metastasis of breast cancer profoundly affects the cognitive and sensory functions as well as morbidity of patients, and the 1 year survival rate among these patients remains less than 20%. However, the pathological mechanism of brain metastasis is as yet poorly understood. In this report, we found that metastat...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201201623
更新日期:2013-03-01 00:00:00