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Schizophrenia Hippocampus

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https://www.readbyqxmd.com/read/28539393/phencyclidine-pcp-administration-during-neurodevelopment-alters-network-activity-in-prefrontal-cortex-and-hippocampus-in-adult-rats
#1
Celia Kjaerby, Nanna Hovelsø, Nils Ole Dalby, Florence Sotty
Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim of this study was to determine how administration with the NMDA receptor antagonist, phencyclidine (PCP), during neurodevelopment affects functional network changes within the hippocampus and medial prefrontal cortex (mPFC). We recorded field potentials in vivo following electrical brainstem stimulation and observed a suppression of evoked theta power in ventral hippocampus, while evoked gamma power in mPFC was enhanced in rats administered neonatally with PCP...
May 24, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28536974/neonatal-immune-challenge-with-lipopolysaccharide-triggers-long-lasting-sex-and-age-related-behavioral-and-immune-neurotrophic-alterations-in-mice-relevance-to-autism-spectrum-disorders
#2
Charllyany Sabino Custódio, Bruna Stefânia Ferreira Mello, Adriano José Maia Chaves Filho, Camila Nayane de Carvalho Lima, Rafaela Carneiro Cordeiro, Fábio Miyajima, Gislaine Z Réus, Silvânia Maria Mendes Vasconcelos, Tatiana Barichello, João Quevedo, Antônio Carlos de Oliveira, David Freitas de Lucena, Danielle S Macedo
Early-life challenges, particularly infections and stress, are related to neuropsychiatric disorders such as autism and schizophrenia. Here, we conducted a wide range of behavioral tests in periadolescent (postnatal day (PN) 35) and adult (PN70) Swiss mice neonatally challenged with LPS on PN5 and -7, to unveil behavioral alterations triggered by LPS exposure. Immune and neurotrophic (brain-derived neurotrophic factor-BDNF) alterations were determined in the prefrontal cortex (PFC), hippocampus (HC), and hypothalamus (HT)...
May 23, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28536274/mapping-22q11-2-gene-dosage-effects-on-brain-morphometry
#3
Amy Lin, Christopher R K Ching, Ariana Vajdi, Daqiang Sun, Rachel K Jonas, Maria Jalbrzikowski, Leila Kushan-Wells, Laura Pacheco Hansen, Emma Krikorian, Boris Gutman, Deepika Dokoru, Gerhard Helleman, Paul M Thompson, Carrie E Bearden
Reciprocal chromosomal rearrangements at the 22q11.2 locus are associated with elevated risk of neurodevelopmental disorders. The 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Here we conducted the first study of 22q11.2 gene dosage effects on brain structure in a sample of 143 human subjects: 66 with 22q11.2 deletions (22q-del; 32 males), 21 with 22q11...
May 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28534294/brain-derived-neurotrophic-factor-expression-in-individuals-with-schizophrenia-and-healthy-aging-testing-the-accelerated-aging-hypothesis-of-schizophrenia
#4
REVIEW
Farhana Islam, Benoit H Mulsant, Aristotle N Voineskos, Tarek K Rajji
PURPOSE OF REVIEW: Schizophrenia has been hypothesized to be a syndrome of accelerated aging. Brain plasticity is vulnerable to the normal aging process and affected in schizophrenia: brain-derived neurotrophic factor (BDNF) is an important neuroplasticity molecule. The present review explores the accelerated aging hypothesis of schizophrenia by comparing changes in BDNF expression in schizophrenia with aging-associated changes. RECENT FINDINGS: Individuals with schizophrenia show patterns of increased overall mortality, metabolic abnormalities, and cognitive decline normally observed later in life in the healthy population...
July 2017: Current Psychiatry Reports
https://www.readbyqxmd.com/read/28533418/hdac1-links-early-life-stress-to-schizophrenia-like-phenotypes
#5
Sanaz Bahari-Javan, Hristo Varbanov, Rashi Halder, Eva Benito, Lalit Kaurani, Susanne Burkhardt, Heike Anderson-Schmidt, Ion Anghelescu, Monika Budde, Roman M Stilling, Joan Costa, Juan Medina, Detlef E Dietrich, Christian Figge, Here Folkerts, Katrin Gade, Urs Heilbronner, Manfred Koller, Carsten Konrad, Sara Y Nussbeck, Harald Scherk, Carsten Spitzer, Sebastian Stierl, Judith Stöckel, Andreas Thiel, Martin von Hagen, Jörg Zimmermann, Antje Zitzelsberger, Sybille Schulz, Andrea Schmitt, Ivana Delalle, Peter Falkai, Thomas G Schulze, Alexander Dityatev, Farahnaz Sananbenesi, André Fischer
Schizophrenia is a devastating disease that arises on the background of genetic predisposition and environmental risk factors, such as early life stress (ELS). In this study, we show that ELS-induced schizophrenia-like phenotypes in mice correlate with a widespread increase of histone-deacetylase 1 (Hdac1) expression that is linked to altered DNA methylation. Hdac1 overexpression in neurons of the medial prefrontal cortex, but not in the dorsal or ventral hippocampus, mimics schizophrenia-like phenotypes induced by ELS...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28526281/effects-of-maternal-immune-activation-on-brain-arginine-metabolism-of-postnatal-day-2-rat-offspring
#6
Jiaxian Zhang, Yu Jing, Hu Zhang, David K Bilkey, Ping Liu
l-Arginine is a versatile semi-essential amino acid with a number of bioactive metabolites, and altered arginine metabolism has been implicated in the pathogenesis of schizophrenia. Earlier research has demonstrated that maternal immune activation (MIA; a risk factor for schizophrenia) alters arginine metabolism in the prefrontal cortex and hippocampus of the adult offspring. The present study investigated how MIA affected the levels of l-arginine and its downstream metabolites in the whole forebrain, frontal cortex, hippocampus and cerebellum of male and female rat offspring at the age of postnatal day 2...
May 16, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28521048/altered-coupling-between-resting-state-cerebral-blood-flow-and-functional-connectivity-in-schizophrenia
#7
Jiajia Zhu, Chuanjun Zhuo, Lixue Xu, Feng Liu, Wen Qin, Chunshui Yu
Background: Respective changes in resting-state cerebral blood flow (CBF) and functional connectivity in schizophrenia have been reported. However, their coupling alterations in schizophrenia remain largely unknown. Methods: 89 schizophrenia patients and 90 sex- and age-matched healthy controls underwent resting-state functional MRI to calculate functional connectivity strength (FCS) and arterial spin labeling imaging to compute CBF. The CBF-FCS coupling of the whole gray matter and the CBF/FCS ratio (the amount of blood supply per unit of connectivity strength) of each voxel were compared between the 2 groups...
May 17, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28509906/therapeutic-efficacy-of-atypical-antipsychotic-drugs-by-targeting-multiple-stress-related-metabolic-pathways
#8
H L Cai, P Jiang, Q Y Tan, R L Dang, M M Tang, Y Xue, Y Deng, B K Zhang, P F Fang, P Xu, D X Xiang, H D Li, J K Yao
Schizophrenia (SZ) is considered to be a multifactorial brain disorder with defects involving many biochemical pathways. Patients with SZ show variable responses to current pharmacological treatments of SZ because of the heterogeneity of this disorder. Stress has a significant role in the pathophysiological pathways and therapeutic responses of SZ. Atypical antipsychotic drugs (AAPDs) can modulate the stress response of the hypothalamic-pituitary-adrenal (HPA) axis and exert therapeutic effects on stress by targeting the prefrontal cortex (PFC) and hippocampus...
May 16, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28507318/cerebellar-volume-and-cerebellocerebral-structural-covariance-in-schizophrenia-a-multisite-mega-analysis-of-983-patients-and-1349-healthy-controls
#9
T Moberget, N T Doan, D Alnæs, T Kaufmann, A Córdova-Palomera, T V Lagerberg, J Diedrichsen, E Schwarz, M Zink, S Eisenacher, P Kirsch, E G Jönsson, H Fatouros-Bergman, L Flyckt, G Pergola, T Quarto, A Bertolino, D Barch, A Meyer-Lindenberg, I Agartz, O A Andreassen, L T Westlye
Although cerebellar involvement across a wide range of cognitive and neuropsychiatric phenotypes is increasingly being recognized, previous large-scale studies in schizophrenia (SZ) have primarily focused on supratentorial structures. Hence, the across-sample reproducibility, regional distribution, associations with cerebrocortical morphology and effect sizes of cerebellar relative to cerebral morphological differences in SZ are unknown. We addressed these questions in 983 patients with SZ spectrum disorders and 1349 healthy controls (HCs) from 14 international samples, using state-of-the-art image analysis pipelines optimized for both the cerebellum and the cerebrum...
May 16, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28505127/variability-of-dna-methylation-within-schizophrenia-risk-loci-across-subregions-of-human-hippocampus
#10
W Brad Ruzicka, Sivan Subburaju, Francine M Benes
Identification of 108 genomic regions significantly associated with schizophrenia risk by the Psychiatric Genomics Consortium was a milestone for the field, and much work is now focused on determining the mechanism of risk associated with each locus. Within these regions, we investigated variability of DNA methylation, a low-level cellular phenotype closely linked to genotype, in two highly similar cellular populations sampled from the human hippocampus, to draw inferences about the elaboration of genotype to phenotype within these loci enriched for schizophrenia risk...
May 15, 2017: Genes
https://www.readbyqxmd.com/read/28502262/effects-of-combined-iugr-and-prenatal-stress-on-the-development-of-the-hippocampus-in-a-fetal-guinea-pig-model
#11
A L Cumberland, H K Palliser, P Rani, D W Walker, J J Hirst
Intrauterine growth restriction (IUGR) and maternal stress during pregnancy are two compromises that negatively impact neurodevelopment and increase the risk of developing later life neuropsychiatric disorders such as schizophrenia, depression and behavioural disorders. Neurosteroids, particularly allopregnanolone, are important in protecting the developing brain and promoting many essential neurodevelopmental processes. Individually, IUGR and prenatal stress (PS) reduce myelination and neurogenesis within affected fetal brains, however less information is available on the combined effects of these two disorders on the term fetal brain...
May 15, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/28499489/neuronal-pas-domain-proteins-1-and-3-are-master-regulators-of-neuropsychiatric-risk-genes
#12
Jacob J Michaelson, Min-Kyoo Shin, Jin-Young Koh, Leo Brueggeman, Angela Zhang, Aaron Katzman, Latisha McDaniel, Mimi Fang, Miles Pufall, Andrew A Pieper
BACKGROUND: NPAS3 has been established as a robust genetic risk factor in major mental illness. In mice, loss of neuronal PAS domain protein 3 (NPAS3) impairs postnatal hippocampal neurogenesis, while loss of the related protein NPAS1 promotes it. These and other findings suggest a critical role for NPAS proteins in neuropsychiatric functioning, prompting interest in the molecular pathways under their control. METHODS: We used RNA sequencing coupled with chromatin immunoprecipitation sequencing to identify genes directly regulated by NPAS1 and NPAS3 in the hippocampus of wild-type, Npas1(-/-), and Npas3(-/-) mice...
April 6, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28498274/fornix-structural-connectivity-and-allostatic-load-empirical-evidence-from-schizophrenia-patients-and-healthy-controls
#13
Anya Savransky, Joshua Chiappelli, Laura M Rowland, Krista Wisner, Dinesh K Shukla, Peter Kochunov, L Elliot Hong
OBJECTIVE: The fornix is a white matter tract carrying the fibers connecting the hippocampus and the hypothalamus, two essential stress-regulatory structures of the brain. We tested the hypothesis that allostatic load (AL), derived from a battery of peripheral biomarkers indexing the cumulative effects of stress, is associated with abnormalities in brain white matter microstructure, especially the fornix; and that higher AL may help explain the white matter abnormalities in schizophrenia...
May 12, 2017: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28485732/pdxdc1-modulates-prepulse-inhibition-of-acoustic-startle-in-the-mouse
#14
L A Feldcamp, P C Boutros, R Raymond, P J Fletcher, J N Nobrega, A H C Wong
Current antipsychotic medications used to treat schizophrenia all target the dopamine D2 receptor. Although these drugs have serious side effects and limited efficacy, no novel molecular targets for schizophrenia treatment have been successfully translated into new medications. To identify novel potential treatment targets for schizophrenia, we searched for previously unknown molecular modulators of acoustic prepulse inhibition (PPI), a schizophrenia endophenotype, in the mouse. We examined six inbred mouse strains that have a range of PPI, and used microarrays to determine which mRNA levels correlated with PPI across these mouse strains...
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28485405/investigating-the-neuroimmunogenic-architecture-of-schizophrenia
#15
R Birnbaum, A E Jaffe, Q Chen, J H Shin, J E Kleinman, T M Hyde, D R Weinberger
The role of the immune system in schizophrenia remains controversial despite numerous studies to date. Most studies have profiled expression of select genes or proteins in peripheral blood, but none have focused on the expression of canonical pathways that mediate overall immune response. The current study used a systematic genetic approach to investigate the role of the immune system in a large sample of post-mortem brain of patients with schizophrenia: RNA sequencing was performed to assess the differential expression of 561 immune genes and 20 immune pathways in dorsolateral prefrontal cortex (DLPFC) (144 schizophrenia and 196 control subjects) and hippocampus (83 schizophrenia and 187 control subjects)...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28485403/gad1-alternative-transcripts-and-dna-methylation-in-human-prefrontal-cortex-and-hippocampus-in-brain-development-schizophrenia
#16
R Tao, K N Davis, C Li, J H Shin, Y Gao, A E Jaffe, M C Gondré-Lewis, D R Weinberger, J E Kleinman, T M Hyde
Genetic variations and adverse environmental events in utero or shortly after birth can lead to abnormal brain development and increased risk of schizophrenia. γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain, plays a vital role in normal brain development. GABA synthesis is controlled by enzymes derived from two glutamic acid decarboxylase (GAD) genes, GAD1 and GAD2, both of which produce transcript isoforms. While the full-length GAD1 transcript (GAD67) has been implicated in the neuropathology of schizophrenia, the transcript structure of GAD1 in the human brain has not been fully characterized...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28483022/expression-of-disrupted-in-schizophrenia-1-in-hippocampus-in-postpartum-depression-animal-models-induced-by-pre-pregnancy-stress
#17
Baomei Xia, Chang Chen, Hailou Zhang, Xin Zhou, Weiwei Tao, Haoxin Wu, Gang Chen
Objective To establish a postpartum depression animal model induced by pre-pregnancy stress,assess abnormal maternal depressive-like behavior,observe the expression of disrupted-in-schizophrenia 1 (DISC1) in the hippocampus,and detect serum estradiol and corticosterone.Methods A total of 32 female Balb/c were assigned to two groups using random number table:the control group and the pre-pregnancy stressed group(model group),and the model group was subjected to 3 weeks of chronic restraint stress. After the last stressor,the control group and the model group were housed with a male...
April 20, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/28480579/longitudinal-epigenetic-predictors-of-amygdala-hippocampus-volume-ratio
#18
Esther Walton, Charlotte A M Cecil, Matthew Suderman, Jingyu Liu, Jessica A Turner, Vince Calhoun, Stefan Ehrlich, Caroline L Relton, Edward D Barker
BACKGROUND: The ratio between amygdala:hippocampal (AH) volume has been associated with multiple psychiatric problems, including anxiety and aggression. Yet, little is known about its biological underpinnings. Here, we used a methylome-wide approach to test (a) whether DNA methylation in early life (birth, age 7) prospectively associates with total AH volume ratio in early adulthood, and (b) whether significant DNA methylation markers are influenced by prenatal risk factors. METHODS: Analyses were based on a subsample (n = 109 males) from the Avon Longitudinal Study of Parents and Children, which included measures of prenatal risk, DNA methylation (Infinium Illumina 450k), T1-weighted brain scans and psychopathology in early adulthood (age 18-21)...
May 8, 2017: Journal of Child Psychology and Psychiatry, and Allied Disciplines
https://www.readbyqxmd.com/read/28479324/theta-oscillations-during-active-sleep-synchronize-the-developing-rubro-hippocampal-sensorimotor-network
#19
Carlos Del Rio-Bermudez, Jangjin Kim, Greta Sokoloff, Mark S Blumberg
Neuronal oscillations comprise a fundamental mechanism by which distant neural structures establish and express functional connectivity. Long-range functional connectivity between the hippocampus and other forebrain structures is enabled by theta oscillations. Here, we show for the first time that the infant rat red nucleus (RN)-a brainstem sensorimotor structure-exhibits theta (4-7 Hz) oscillations restricted primarily to periods of active (REM) sleep. At postnatal day 8 (P8), theta is expressed as brief bursts immediately following myoclonic twitches; by P12, theta oscillations are expressed continuously across bouts of active sleep...
May 22, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28479102/septal-cholinergic-neuromodulation-tunes-the-astrocyte-dependent-gating-of-hippocampal-nmda-receptors-to-wakefulness
#20
Thomas Papouin, Jaclyn M Dunphy, Michaela Tolman, Kelly T Dineley, Philip G Haydon
The activation of the N-methyl D-aspartate receptor (NMDAR) is controlled by a glutamate-binding site and a distinct, independently regulated, co-agonist-binding site. In most brain regions, the NMDAR co-agonist is the astrocyte-derived gliotransmitter D-serine. We found that D-serine levels oscillate in mouse hippocampus as a function of wakefulness, in vitro and in vivo. This causes a full saturation of the NMDAR co-agonist site in the dark (active) phase that dissipates to sub-saturating levels during the light (sleep) phase, and influences learning performance throughout the day...
May 17, 2017: Neuron
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