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neurogenesis psychiatry

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https://www.readbyqxmd.com/read/28555078/tau-dependent-suppression-of-adult-neurogenesis-in-the-stressed-hippocampus
#1
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...
May 30, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28485407/lipocalin-2-regulates-adult-neurogenesis-and-contextual-discriminative-behaviours
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
November 29, 2016: 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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/27200462/combining-psychodynamic-psychotherapy-and-pharmacotherapy
#15
Jack M Gorman
Many patients with depression, anxiety disorders, and other psychiatric disorders are treated with combinations of psychodynamic psychotherapy and medication. Whether this is better than monotherapy is an empirical question that requires much more extensive research than is currently available. When medications were first introduced to treat psychiatric illnesses, some psychopharmacologists insisted that it heralded a new area of "biological psychiatry" that would ultimately render psychotherapy obsolete. Psychodynamic theorists and practitioners, on the other hand, argued that psychopharmacology offered only a superficial approach to treatment...
December 0: Psychodynamic Psychiatry
https://www.readbyqxmd.com/read/26995153/the-role-of-gsk-3-in-treatment-resistant-depression-and-links-with-the-pharmacological-effects-of-lithium-and-ketamine-a-review-of-the-literature
#16
REVIEW
J F Costemale-Lacoste, J P Guilloux, R Gaillard
BACKGROUND: Since the discovery of antidepressants, new treatments have emerged with fewer side effects but no greater efficacy. Glycogen synthase kinase 3 β (GSK-3β), a kinase known for its activity on glycogen synthesis, has in the last few years raised growing interest in biological psychiatry. Several efficient treatments in major depression have an inhibitory effect on this kinase, which could be targeted in new mood disorder treatments. METHODS: The aim of this review is to summarize findings concerning the intracellular pharmacologic effects of GSK-3β inhibitors on mood...
April 2016: L'Encéphale
https://www.readbyqxmd.com/read/26922521/the-effect-of-lithium-on-hematopoietic-mesenchymal-and-neural-stem-cells
#17
REVIEW
Ewa Ferensztajn-Rochowiak, Janusz K Rybakowski
Lithium has been used in modern psychiatry for more than 65 years, constituting a cornerstone for the long-term treatment of bipolar disorder. A number of biological properties of lithium have been discovered, including its hematological, antiviral and neuroprotective effects. In this article, a systematic review of the effect of lithium on hematopoietic, mesenchymal and neural stem cells is presented. The beneficial effects of lithium on the level of hematopoietic stem cells (HSC) and growth factors have been reported since 1970s...
April 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/26809838/revisiting-adult-neurogenesis-and-the-role-of-erythropoietin-for-neuronal-and-oligodendroglial-differentiation-in-the-hippocampus
#18
I Hassouna, C Ott, L Wüstefeld, N Offen, R A Neher, M Mitkovski, D Winkler, S Sperling, L Fries, S Goebbels, I C Vreja, N Hagemeyer, M Dittrich, M F Rossetti, K Kröhnert, K Hannke, S Boretius, A Zeug, C Höschen, T Dandekar, E Dere, E Neher, S O Rizzoli, K-A Nave, A-L Sirén, H Ehrenreich
Recombinant human erythropoietin (EPO) improves cognitive performance in neuropsychiatric diseases ranging from schizophrenia and multiple sclerosis to major depression and bipolar disease. This consistent EPO effect on cognition is independent of its role in hematopoiesis. The cellular mechanisms of action in brain, however, have remained unclear. Here we studied healthy young mice and observed that 3-week EPO administration was associated with an increased number of pyramidal neurons and oligodendrocytes in the hippocampus of ~20%...
December 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/26645631/fluoxetine-effects-on-molecular-cellular-and-behavioral-endophenotypes-of-depression-are-driven-by-the-living-environment
#19
S Alboni, R M van Dijk, S Poggini, G Milior, M Perrotta, T Drenth, N Brunello, D P Wolfer, C Limatola, I Amrein, F Cirulli, L Maggi, I Branchi
Selective serotonin reuptake inhibitors (SSRIs) represent the most common treatment for major depression. However, their efficacy is variable and incomplete. In order to elucidate the cause of such incomplete efficacy, we explored the hypothesis positing that SSRIs may not affect mood per se but, by enhancing neural plasticity, render the individual more susceptible to the influence of the environment. Consequently, SSRI administration in a favorable environment promotes a reduction of symptoms, whereas in a stressful environment leads to a worse prognosis...
April 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/26552589/molecular-systems-evaluation-of-oligomerogenic-app-e693q-and-fibrillogenic-app-km670-671nl-psen1-%C3%AE-exon9-mouse-models-identifies-shared-features-with-human-alzheimer-s-brain-molecular-pathology
#20
B Readhead, J-V Haure-Mirande, B Zhang, V Haroutunian, S Gandy, E E Schadt, J T Dudley, M E Ehrlich
Identification and characterization of molecular mechanisms that connect genetic risk factors to initiation and evolution of disease pathophysiology represent major goals and opportunities for improving therapeutic and diagnostic outcomes in Alzheimer's disease (AD). Integrative genomic analysis of the human AD brain transcriptome holds potential for revealing novel mechanisms of dysfunction that underlie the onset and/or progression of the disease. We performed an integrative genomic analysis of brain tissue-derived transcriptomes measured from two lines of mice expressing distinct mutant AD-related proteins...
August 2016: Molecular Psychiatry
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