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neurogenesis psychiatry

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https://www.readbyqxmd.com/read/28948974/a-upf3b-mutant-mouse-model-with-behavioral-and-neurogenesis-defects
#1
L Huang, E Y Shum, S H Jones, C-H Lou, J Dumdie, H Kim, A J Roberts, L A Jolly, J L Espinoza, D M Skarbrevik, M H Phan, H Cook-Andersen, N R Swerdlow, J Gecz, M F Wilkinson
Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA degradation pathway that acts on RNAs terminating their reading frames in specific contexts. NMD is regulated in a tissue-specific and developmentally controlled manner, raising the possibility that it influences developmental events. Indeed, loss or depletion of NMD factors have been shown to disrupt developmental events in organisms spanning the phylogenetic scale. In humans, mutations in the NMD factor gene, UPF3B, cause intellectual disability (ID) and are strongly associated with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia (SCZ)...
September 26, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28941093/staging-in-bipolar-disorder-from-theoretical-framework-to-clinical-utility
#2
Michael Berk, Robert Post, Aswin Ratheesh, Emma Gliddon, Ajeet Singh, Eduard Vieta, Andre F Carvalho, Melanie M Ashton, Lesley Berk, Susan M Cotton, Patrick D McGorry, Brisa S Fernandes, Lakshmi N Yatham, Seetal Dodd
Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at-risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end-stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures...
October 2017: World Psychiatry: Official Journal of the World Psychiatric Association (WPA)
https://www.readbyqxmd.com/read/28924182/an-in-vitro-model-of-lissencephaly-expanding-the-role-of-dcx-during-neurogenesis
#3
M Shahsavani, R J Pronk, R Falk, M Lam, M Moslem, S B Linker, J Salma, K Day, J Schuster, B-M Anderlid, N Dahl, F H Gage, A Falk
Lissencephaly comprises a spectrum of brain malformations due to impaired neuronal migration in the developing cerebral cortex. Classical lissencephaly is characterized by smooth cerebral surface and cortical thickening that result in seizures, severe neurological impairment and developmental delay. Mutations in the X-chromosomal gene DCX, encoding doublecortin, is the main cause of classical lissencephaly. Much of our knowledge about DCX-associated lissencephaly comes from post-mortem analyses of patient's brains, mainly since animal models with DCX mutations do not mimic the disease...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28827761/copy-number-elevation-of-22q11-2-genes-arrests-the-developmental-maturation-of-working-memory-capacity-and-adult-hippocampal-neurogenesis
#4
S Boku, T Izumi, S Abe, T Takahashi, A Nishi, H Nomaru, Y Naka, G Kang, M Nagashima, A Hishimoto, S Enomoto, G Duran-Torres, K Tanigaki, J Zhang, K Ye, S Kato, P T Männistö, K Kobayashi, N Hiroi
Working memory capacity, a critical component of executive function, expands developmentally from childhood through adulthood. Anomalies in this developmental process are seen in individuals with autism spectrum disorder (ASD), schizophrenia and intellectual disabilities (ID), implicating this atypical process in the trajectory of developmental neuropsychiatric disorders. However, the cellular and neuronal substrates underlying this process are not understood. Duplication and triplication of copy number variants of 22q11...
August 22, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28809400/prenatal-one-carbon-metabolism-dysregulation-programs-schizophrenia-like-deficits
#5
A Alachkar, L Wang, R Yoshimura, A R Hamzeh, Z Wang, N Sanathara, S M Lee, X Xu, G W Abbott, O Civelli
The methionine-folate cycle-dependent one-carbon metabolism is implicated in the pathophysiology of schizophrenia. Since schizophrenia is a developmental disorder, we examined the effects that perturbation of the one-carbon metabolism during gestation has on mice progeny. Pregnant mice were administered methionine equivalent to double their daily intake during the last week of gestation. Their progeny (MET mice) exhibited schizophrenia-like social deficits, cognitive impairments and elevated stereotypy, decreased neurogenesis and synaptic plasticity, and abnormally reduced local excitatory synaptic connections in CA1 neurons...
August 15, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28809398/precision-medicine-for-suicidality-from-universality-to-subtypes-and-personalization
#6
A B Niculescu, H Le-Niculescu, D F Levey, P L Phalen, H L Dainton, K Roseberry, E M Niculescu, J O Niezer, A Williams, D L Graham, T J Jones, V Venugopal, A Ballew, M Yard, T Gelbart, S M Kurian, A Shekhar, N J Schork, G E Sandusky, D R Salomon
Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies...
September 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28555078/tau-dependent-suppression-of-adult-neurogenesis-in-the-stressed-hippocampus
#7
C Dioli, P Patrício, R Trindade, L G Pinto, J M Silva, M Morais, E Ferreiro, S Borges, A Mateus-Pinheiro, A J Rodrigues, N Sousa, J M Bessa, L Pinto, I Sotiropoulos
Stress, a well-known sculptor of brain plasticity, is shown to suppress hippocampal neurogenesis in the adult brain; yet, the underlying cellular mechanisms are poorly investigated. Previous studies have shown that chronic stress triggers hyperphosphorylation and accumulation of the cytoskeletal protein Tau, a process that may impair the cytoskeleton-regulating role(s) of this protein with impact on neuronal function. Here, we analyzed the role of Tau on stress-driven suppression of neurogenesis in the adult dentate gyrus (DG) using animals lacking Tau (Tau-knockout; Tau-KO) and wild-type (WT) littermates...
August 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28485407/lipocalin-2-regulates-adult-neurogenesis-and-contextual-discriminative-behaviours
#8
A C Ferreira, T Santos, B Sampaio-Marques, A Novais, S D Mesquita, P Ludovico, L Bernardino, M Correia-Neves, N Sousa, J A Palha, J C Sousa, F Marques
In the adult mammalian brain, newborn granule cells are continuously integrated into hippocampal circuits, and the fine-tuning of this process is important for hippocampal function. Thus, the identification of factors that control adult neural stem cells (NSCs) maintenance, differentiation and integration is essential. Here we show that the deletion of the iron trafficking protein lipocalin-2 (LCN2) induces deficits in NSCs proliferation and commitment, with impact on the hippocampal-dependent contextual fear discriminative task...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28485406/inducing-a-long-term-potentiation-in-the-dentate-gyrus-is-sufficient-to-produce-rapid-antidepressant-like-effects
#9
A Kanzari, C Bourcier-Lucas, A Freyssin, D N Abrous, N Haddjeri, G Lucas
Recent hypotheses propose that one prerequisite to obtain a rapid antidepressant (AD) effect would reside in processes of synaptic reinforcement occurring within the dentate gyrus (DG) of the hippocampus independently from neurogenesis. However, to date no relationship has been established between an increased DG synaptic plasticity, and rapid AD-like action. To the best of our knowledge, this study shows for the first time that inducing a long-term potentiation (LTP) within the DG by stimulating the perforant pathway (PP) is sufficient to induce such effects...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28439104/a-novel-5ht3-receptor-igf1-mechanism-distinct-from-ssri-induced-antidepressant-effects
#10
M Kondo, Y Koyama, Y Nakamura, S Shimada
Depression is a common mental disorder affecting around 350 million people worldwide. Although selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, a significant proportion of depressed patients do not achieve remission with SSRIs. In this study, we show that a serotonin type 3 receptor (5HT3R) agonist induces antidepressant effects as well as hippocampal neurogenesis independent of fluoxetine (a commonly used SSRI). Notably, our histological analysis reveals that 5HT3R and insulin-like growth factor 1 (IGF1) are expressed in the same neurons in the subgranular zone of the hippocampal dentate gyrus...
April 25, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28439102/mecp2-regulated-mirnas-control-early-human-neurogenesis-through-differential-effects-on-erk-and-akt-signaling
#11
N Mellios, D A Feldman, S D Sheridan, J P K Ip, S Kwok, S K Amoah, B Rosen, B A Rodriguez, B Crawford, R Swaminathan, S Chou, Y Li, M Ziats, C Ernst, R Jaenisch, S J Haggarty, M Sur
Rett syndrome (RTT) is an X-linked, neurodevelopmental disorder caused primarily by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, which encodes a multifunctional epigenetic regulator with known links to a wide spectrum of neuropsychiatric disorders. Although postnatal functions of MeCP2 have been thoroughly investigated, its role in prenatal brain development remains poorly understood. Given the well-established importance of microRNAs (miRNAs) in neurogenesis, we employed isogenic human RTT patient-derived induced pluripotent stem cell (iPSC) and MeCP2 short hairpin RNA knockdown approaches to identify novel MeCP2-regulated miRNAs enriched during early human neuronal development...
April 25, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28348387/a-synthetic-small-molecule-isoxazole-9-protects-against-methamphetamine-relapse
#12
M H Galinato, J W Lockner, M J Fannon-Pavlich, J C Sobieraj, M C Staples, S S Somkuwar, A Ghofranian, S Chaing, A I Navarro, A Joea, B W Luikart, K D Janda, C Heyser, G F Koob, C D Mandyam
Adult neurogenesis in the dentate gyrus (DG) is strongly influenced by drug-taking behavior and may have a role in the etiology of drug-seeking behavior. However, mechanistic studies on the relationship of neurogenesis on drug seeking are limited. Outbred Wistar rats experienced extended access methamphetamine self-administration and individual differences in drug taking defined animals with higher preferred and lower preferred levels of drug intake. Forced abstinence from higher preferred levels of drug taking enhanced neurogenesis and neuronal activation of granule cell neurons (GCNs) in the DG and produced compulsive-like drug reinstatement...
March 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/27895323/elevated-cyp2c19-expression-is-associated-with-depressive-symptoms-and-hippocampal-homeostasis-impairment
#13
M M Jukić, N Opel, J Ström, T Carrillo-Roa, S Miksys, M Novalen, A Renblom, S C Sim, E M Peñas-Lledó, P Courtet, A Llerena, B T Baune, D J de Quervain, A Papassotiropoulos, R F Tyndale, E B Binder, U Dannlowski, M Ingelman-Sundberg
The polymorphic CYP2C19 enzyme metabolizes psychoactive compounds and is expressed in the adult liver and fetal brain. Previously, we demonstrated that the absence of CYP2C19 is associated with lower levels of depressive symptoms in 1472 Swedes. Conversely, transgenic mice carrying the human CYP2C19 gene (2C19TG) have shown an anxious phenotype and decrease in hippocampal volume and adult neurogenesis. The aims of this study were to: (1) examine whether the 2C19TG findings could be translated to humans, (2) evaluate the usefulness of the 2C19TG strain as a tool for preclinical screening of new antidepressants and (3) provide an insight into the molecular underpinnings of the 2C19TG phenotype...
August 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/27843149/jnk1-controls-adult-hippocampal-neurogenesis-and-imposes-cell-autonomous-control-of-anxiety-behaviour-from-the-neurogenic-niche
#14
H Mohammad, F Marchisella, S Ortega-Martinez, P Hollos, K Eerola, E Komulainen, N Kulesskaya, E Freemantle, V Fagerholm, E Savontous, H Rauvala, B D Peterson, H van Praag, E T Coffey
Promoting adult hippocampal neurogenesis is expected to induce neuroplastic changes that improve mood and alleviate anxiety. However, the underlying mechanisms remain largely unknown and the hypothesis itself is controversial. Here we show that mice lacking Jnk1, or c-Jun N-terminal kinase (JNK) inhibitor-treated mice, display increased neurogenesis in adult hippocampus characterized by enhanced cell proliferation and survival, and increased maturation in the ventral region. Correspondingly, anxiety behaviour is reduced in a battery of tests, except when neurogenesis is prevented by AraC treatment...
November 15, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27777416/ap2%C3%AE-controls-adult-hippocampal-neurogenesis-and-modulates-cognitive-but-not-anxiety-or-depressive-like-behavior
#15
A Mateus-Pinheiro, N D Alves, P Patrício, A R Machado-Santos, E Loureiro-Campos, J M Silva, V M Sardinha, J Reis, H Schorle, J F Oliveira, J Ninkovic, N Sousa, L Pinto
Hippocampal neurogenesis has been proposed to participate in a myriad of behavioral responses, both in basal states and in the context of neuropsychiatric disorders. Here, we identify activating protein 2γ (AP2γ, also known as Tcfap2c), originally described to regulate the generation of neurons in the developing cortex, as a modulator of adult hippocampal glutamatergic neurogenesis in mice. Specifically, AP2γ is present in a sub-population of hippocampal transient amplifying progenitors. There, it is found to act as a positive regulator of the cell fate determinants Tbr2 and NeuroD, promoting proliferation and differentiation of new glutamatergic granular neurons...
October 25, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27752076/peripheral-administration-of-lactate-produces-antidepressant-like-effects
#16
A Carrard, M Elsayed, M Margineanu, B Boury-Jamot, L Fragnière, E M Meylan, J-M Petit, H Fiumelli, P J Magistretti, J-L Martin
In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment...
October 18, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27698430/hippocampal-bone-morphogenetic-protein-signaling-mediates-behavioral-effects-of-antidepressant-treatment
#17
S M Brooker, K T Gobeske, J Chen, C-Y Peng, J A Kessler
Many antidepressants stimulate adult hippocampal neurogenesis, but the mechanisms by which they increase neurogenesis and modulate behavior are incompletely understood. Here we show that hippocampal bone morphogenetic protein (BMP) signaling is modulated by antidepressant treatment, and that the changes in BMP signaling mediate effects of antidepressant treatment on neural progenitor cell proliferation and behavior. Treatment with the selective serotonin reuptake inhibitor fluoxetine suppressed BMP signaling in the adult mouse hippocampus both by decreasing levels of BMP4 ligand and increasing production of the BMP inhibitor noggin...
June 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/27457812/exome-sequencing-of-pakistani-consanguineous-families-identifies-30-novel-candidate-genes-for-recessive-intellectual-disability
#18
S Riazuddin, M Hussain, A Razzaq, Z Iqbal, M Shahzad, D L Polla, Y Song, E van Beusekom, A A Khan, L Tomas-Roca, M Rashid, M Y Zahoor, W M Wissink-Lindhout, M A R Basra, M Ansar, Z Agha, K van Heeswijk, F Rasheed, M Van de Vorst, J A Veltman, C Gilissen, J Akram, T Kleefstra, M Z Assir, D Grozeva, K Carss, F L Raymond, T D O'Connor, S A Riazuddin, S N Khan, Z M Ahmed, A P M de Brouwer, H van Bokhoven, S Riazuddin
Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes...
July 26, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27378147/altered-proliferation-and-networks-in-neural-cells-derived-from-idiopathic-autistic-individuals
#19
Maria C Marchetto, Haim Belinson, Yuan Tian, Beatriz C Freitas, Chen Fu, Krishna Vadodaria, Patricia Beltrao-Braga, Cleber A Trujillo, Ana P D Mendes, Krishnan Padmanabhan, Yanelli Nunez, Jing Ou, Himanish Ghosh, Rebecca Wright, Kristen Brennand, Karen Pierce, Lawrence Eichenfield, Tiziano Pramparo, Lisa Eyler, Cynthia C Barnes, Eric Courchesne, Daniel H Geschwind, Fred H Gage, Anthony Wynshaw-Boris, Alysson R Muotri
Autism spectrum disorders (ASD) are common, complex and heterogeneous neurodevelopmental disorders. Cellular and molecular mechanisms responsible for ASD pathogenesis have been proposed based on genetic studies, brain pathology and imaging, but a major impediment to testing ASD hypotheses is the lack of human cell models. Here, we reprogrammed fibroblasts to generate induced pluripotent stem cells, neural progenitor cells (NPCs) and neurons from ASD individuals with early brain overgrowth and non-ASD controls with normal brain size...
June 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/27378146/a-chromosome-16p13-11-microduplication-causes-hyperactivity-through-dysregulation-of-mir-484-protocadherin-19-signaling
#20
M Fujitani, S Zhang, R Fujiki, Y Fujihara, T Yamashita
Chromosome 16p13.11 microduplication is a risk factor associated with various neurodevelopmental disorders such as attention-deficit/hyperactivity disorder, intellectual disabilities, developmental delay and autistic spectrum disorder. The underlying molecular mechanism of this genetic variation remained unknown, but its core genetic locus-conserved across mice and humans-contains seven genes. Here, we generated bacterial artificial chromosome-transgenic mice carrying a human 16p13.11 locus, and these mice showed the behavioral hyperactivity phenotype...
March 2017: Molecular Psychiatry
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