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Schizophrenia Hippocampus

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https://www.readbyqxmd.com/read/28334860/genetic-regulation-of-gene-expression-in-the-epileptic-human-hippocampus
#1
Nasir Mirza, Richard Appleton, Sasha Burn, Daniel du Plessis, Roderick Duncan, Jibril Osman Farah, Bjarke Feenstra, Anders Hviid, Vivek Josan, Rajiv Mohanraj, Arif Shukralla, Graeme J Sills, Anthony G Marson, Munir Pirmohamed
Epilepsy is a serious and common neurological disorder. Expression quantitative loci (eQTL) analysis is a vital aid for the identification and interpretation of disease-risk loci. Many eQTLs operate in a tissue- and condition-specific manner. We have performed the first genome-wide cis-eQTL analysis of human hippocampal tissue to include not only normal (n = 22) but also epileptic (n = 22) samples. We demonstrate that disease-associated variants from an epilepsy GWAS meta-analysis and a febrile seizures (FS) GWAS are significantly more enriched with epilepsy-eQTLs than with normal hippocampal eQTLs from two larger independent published studies...
March 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28323012/extracellular-matrix-alterations-in-the-ketamine-model-of-schizophrenia
#2
Gabriela Matuszko, Sebastiano Curreli, Rahul Kaushik, Axel Becker, Alexander Dityatev
The neural extracellular matrix (ECM) plays an important role in regulation of perisomatic GABAergic inhibition and synaptic plasticity in the hippocampus and cortex. Decreased labeling of perineuronal nets, a form of ECM predominantly associated with parvalbumin-expressing interneurons in the brain, has been observed in post-mortem studies of schizophrenia patients, specifically, in brain areas such as prefrontal cortex, entorhinal cortex, and amygdala. Moreover, glial ECM in the form of dandelion clock-like structures was reported to be altered in schizophrenia patients...
March 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28302570/hippocampal-endothelin-1-decreases-excitability-of-pyramidal-neurons-and-produces-anxiolytic-effects
#3
Ming Chen, Shu Shu, Huan-Huan Yan, Lei Pei, Ze-Fen Wang, Qi Wan, Lin-Lin Bi
Anxiety disorders contribute to the pathophysiology of psychiatric diseases, including major depression, substance abuse, and schizophrenia. The hippocampus is important for anxiety modulation. However, the mechanisms that control the neuronal activity of the hippocampus in anxiety are still not clear. We found that Endothelin-1 (ET1) mRNA in the hippocampus was down-regulated in high-anxiety mice. Neutralizing endogenous ET1 in the hippocampal CA1 enhanced anxiety-like behaviors. We next revealed that most expression of ET1 and its receptors in the CA1 takes place in pyramidal neurons, and the ET1 signaling pathway directly regulated the excitability of CA1 pyramidal neurons and glutamatergic synaptic neurotransmission...
March 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28295046/transcriptomic-immaturity-of-the-hippocampus-and-prefrontal-cortex-in-patients-with-alcoholism
#4
Tomoyuki Murano, Hisatsugu Koshimizu, Hideo Hagihara, Tsuyoshi Miyakawa
Alcoholism, which is defined as the recurring harmful use of alcohol despite its negative consequences, has a lifetime prevalence of 17.8%. Previous studies have shown that chronic alcohol consumption disrupts various brain functions and behaviours. However, the precise mechanisms that underlie alcoholism are currently unclear. Recently, we discovered "pseudo-immature" brain cell states of the dentate gyrus and prefrontal cortex (PFC) in mouse models of psychotic disorders and epileptic seizure. Similar pseudo-immaturity has been observed in patients with psychotic disorders, such as schizophrenia and bipolar disorder...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28293111/influence-of-cfh-gene-on-symptom-severity-of-schizophrenia
#5
Chen Zhang, Qinyu Lv, Weixing Fan, Wei Tang, Zhenghui Yi
OBJECTIVE: Recent advances have provided compelling evidence for the role of excessive complement activity in the pathophysiology of schizophrenia. In this study, we aimed to detect the association of the gene encoding complement factor H (CFH), a regulator in complement activation, with schizophrenia. MATERIALS AND METHODS: A sample of 1783 individuals with or without schizophrenia was recruited for genetic analysis. Genomic DNA samples were extracted from peripheral blood cells using multiplex polymerase chain reaction and the SNaPshot assay...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28288855/alterations-in-prefrontal-connectivity-in-schizophrenia-assessed-using-diffusion-magnetic-resonance-imaging
#6
Vicente Molina, Alba Lubeiro, Oscar Soto, Margarita Rodriguez, Aldara Álvarez, Rebeca Hernández, Rodrigo de Luis-García
BACKGROUND: Spatial and biological characteristics of structural frontal disconnectivity in schizophrenia remain incompletely understood. Simultaneous streamline count (SC) and fractional anisotropy (FA) analyses may yield relevant complementary information to this end. METHODS: Using 3T diffusion magnetic resonance imaging both SC and FA were calculated for the tracts linking lateral and medial subregions of prefrontal cortex (PFC) to cingulate, hippocampus, caudate and thalamus in 27 schizophrenia patients (14 first-episodes) and 27 controls...
March 10, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28283559/a-rare-variant-identified-within-the-glun2b-c-terminus-in-a-patient-with-autism-affects-nmda-receptor-surface-expression-and-spine-density
#7
Shuxi Liu, Liang Zhou, Hongjie Yuan, Marta Vieira, Antonio Sanz-Clemente, John D Badger, Wei Lu, Stephen F Traynelis, Katherine W Roche
NMDA receptors (NMDARs) are ionotropic glutamate receptors that are crucial for neuronal development and higher cognitive processes. NMDAR dysfunction is involved in a variety of neurological and psychiatric diseases; however, the mechanistic link between the human pathology and NMDAR dysfunction is poorly understood. Rare missense variants within NMDAR subunits have been identified in numerous patients with mental or neurological disorders. We specifically focused on the GluN2B NMDAR subunit, which is highly expressed in the hippocampus and cortex throughout development...
March 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28281921/lateralization-of-neurobiological-response-in-adolescents-with-post-traumatic-stress-disorder-related-to-severe-childhood-sexual-abuse-the-tri-modal-reaction-t-mr-model-of-protection
#8
Tuba Mutluer, Vedat Şar, Çiğdem Kose-Demiray, Harun Arslan, Sibel Tamer, Serap Inal, Anıl Ş Kaçar
This study inquires into neurobiological response to stress and its clinical correlates among adolescents with post-traumatic stress disorder (PTSD). Structural magnetic resonance imaging (MRI) measures of cerebral anatomy were carried out on 23 female adolescents with PTSD related to severe childhood sexual abuse and 21 matched healthy controls. Clinician Administered PTSD Scale for Children and Adolescents, Adolescent Dissociative Experiences Scale, Childhood Trauma Questionnaire, Schedule for Affective Disorders and Schizophrenia for School Age Children, Beck Depression Scale and a set of neuro-cognitive tests were administered to all participants...
March 10, 2017: Journal of Trauma & Dissociation
https://www.readbyqxmd.com/read/28280881/tryptophan-depletion-affects-compulsive-behaviour-in-rats-strain-dependent-effects-and-associated-neuromechanisms
#9
A Merchán, S V Navarro, A B Klein, S Aznar, L Campa, C Suñol, M Moreno, P Flores
RATIONALE: Compulsive behaviour, present in different psychiatric disorders, such as obsessive-compulsive disorder, schizophrenia and drug abuse, is associated with altered levels of monoamines, particularly serotonin (5-hydroxytryptamine) and its receptor system. OBJECTIVES: The present study investigated whether 5-HT manipulation, through a tryptophan (TRP) depletion by diet in Wistar and Lister Hooded rats, modulates compulsive drinking in schedule-induced polydipsia (SIP) and locomotor activity in the open-field test...
March 9, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28275713/axonal-type-iii-nrg1-controls-glutamate-synapse-formation-and-glua2-trafficking-in-hippocampal-accumbens-connections
#10
Chongbo Zhong, Wendy Akmentin, Chuang Du, Lorna W Role, David A Talmage
Altered neuregulin 1 (Nrg1)/ErbB signaling and glutamatergic hypofunction have been implicated in the pathophysiology of schizophrenia. Here, we employed gene chimeric ventral hippocampus (vHipp)-nucleus accumbens (nAcc) coculture from mouse, electrophysiology, immunocytochemistry, FM1-43 vesicle fusion, and electron microscopy techniques to examine the pre- and postsynaptic mechanisms of genetic deficits in Nrg1/ErbB signaling-induced glutamatergic dysfunctions. Reduced presynaptic type III Nrg1 expression along vHipp axons decreases the number of glutamate synapses and impairs GluA2 trafficking in the postsynaptic nAcc neurons, resulting in decreased frequency and amplitude of miniature EPSCs (mEPSCs)...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28274820/histamine-induces-kcnq-channel-dependent-gamma-oscillations-in-rat-hippocampus-via-activation-of-the-h1-receptor
#11
Richard Andersson, Dagmar Galter, Daniela Papadia, André Fisahn
Histamine is an aminergic neurotransmitter, which regulates wakefulness, arousal and attention in the central nervous system. Histamine receptors have been the target of efforts to develop pro-cognitive drugs to treat disorders such as Alzheimer's disease and schizophrenia. Cognitive functions including attention are closely associated with gamma oscillations, a rhythmical electrical activity pattern in the 30-80 Hz range, which depends on the synchronized activity of excitatory pyramidal cells and inhibitory fast-spiking interneurons...
March 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28245176/familial-and-environmental-influences-on-brain-volumes-in-twins-with-schizophrenia
#12
Marco M Picchioni, Fruhling Rijsdijk, Timothea Toulopoulou, Christopher Chaddock, James H Cole, Ulrich Ettinger, Ana Oses, Hugo Metcalfe, Robin M Murray, Philip McGuire
BACKGROUND: Reductions in whole brain and grey matter volumes are robust features of schizophrenia, yet their etiological influences are unclear. METHODS: We investigated the association between the genetic and environmental risk for schizophrenia and brain volumes. Whole brain, grey matter and white matter volumes were established from structural MRIs from twins varying in their zygosity and concordance for schizophrenia. Hippocampal volumes were measured manually...
March 2017: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/28242871/attenuation-of-ketamine-induced-impairment-in-verbal-learning-and-memory-in-healthy-volunteers-by-the-ampa-receptor-potentiator-pf-04958242
#13
M Ranganathan, N DeMartinis, B Huguenel, F Gaudreault, M M Bednar, C L Shaffer, S Gupta, J Cahill, M A Sherif, J Mancuso, L Zumpano, D C D'Souza
There is a need to develop treatments for cognitive impairment associated with schizophrenia (CIAS). The significant role played by N-methyl-d-aspartate receptors (NMDARs) in both the pathophysiology of schizophrenia and in neuronal plasticity suggests that facilitation of NMDAR function might ameliorate CIAS. One strategy to correct NMDAR hypofunction is to stimulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as AMPAR and NMDAR functioning are coupled and interdependent. In rats and nonhuman primates (NHP), AMPAR potentiators reduce spatial working memory deficits caused by the nonselective NMDAR antagonist ketamine...
February 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28241130/nardostachys-jatamansi-targets-bdnf-trkb-to-alleviate-ketamine-induced-schizophrenia-like-symptoms-in-rats
#14
Anjali Janardhanan, Anjana Sadanand, Arambakkam Janardhanam Vanisree
OBJECTIVE: Schizophrenia, a common neurological disorder appearing in the late teens or early adulthood, is characterized by disorganized thinking, behaviour, and perception of emotions. Aberrant N-methyl-D-aspartate (NMDA) receptor-mediated synaptic plasticity is a major pathological event here due to dysfunction of dopamine and glutamate transmission at NMDA receptors. De-regulated brain-derived neurotrophic factor (BDNF), i.e., its signalling through the tropomyosin receptor kinase B (TrkB) receptor, is a major feature of schizophrenia...
February 28, 2017: Neuropsychobiology
https://www.readbyqxmd.com/read/28224285/abnormal-effective-connectivity-in-the-brain-is-involved-in-auditory-verbal-hallucinations-in-schizophrenia
#15
Baojuan Li, Long-Biao Cui, Yi-Bin Xi, Karl J Friston, Fan Guo, Hua-Ning Wang, Lin-Chuan Zhang, Yuan-Han Bai, Qing-Rong Tan, Hong Yin, Hongbing Lu
Information flow among auditory and language processing-related regions implicated in the pathophysiology of auditory verbal hallucinations (AVHs) in schizophrenia (SZ) remains unclear. In this study, we used stochastic dynamic causal modeling (sDCM) to quantify connections among the left dorsolateral prefrontal cortex (inner speech monitoring), auditory cortex (auditory processing), hippocampus (memory retrieval), thalamus (information filtering), and Broca's area (language production) in 17 first-episode drug-naïve SZ patients with AVHs, 15 without AVHs, and 19 healthy controls using resting-state functional magnetic resonance imaging...
February 21, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28223982/mouse-model-of-neurological-complications-resulting-from-encephalitic-alphavirus-infection
#16
Shannon E Ronca, Jeanon Smith, Takaaki Koma, Magda M Miller, Nadezhda Yun, Kelly T Dineley, Slobodan Paessler
Long-term neurological complications, termed sequelae, can result from viral encephalitis, which are not well understood. In human survivors, alphavirus encephalitis can cause severe neurobehavioral changes, in the most extreme cases, a schizophrenic-like syndrome. In the present study, we aimed to adapt an animal model of alphavirus infection survival to study the development of these long-term neurological complications. Upon low-dose infection of wild-type C57B/6 mice, asymptomatic and symptomatic groups were established and compared to mock-infected mice to measure general health and baseline neurological function, including the acoustic startle response and prepulse inhibition paradigm...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28220356/overexpression-of-line-1-retrotransposons-in-autism-brain
#17
Svitlana Shpyleva, Stepan Melnyk, Oleksandra Pavliv, Igor Pogribny, S Jill James
Long interspersed nuclear elements-1 (LINE-1 or L1) are mobile DNA sequences that are capable of duplication and insertion (retrotransposition) within the genome. Recently, retrotransposition of L1 was shown to occur within human brain leading to somatic mosaicism in hippocampus and cerebellum. Because unregulated L1 activity can promote genomic instability and mutagenesis, multiple mechanisms including epigenetic chromatin condensation have evolved to effectively repress L1 expression. Nonetheless, L1 expression has been shown to be increased in patients with Rett syndrome and schizophrenia...
February 20, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28220103/hippocampal-damage-and-atrophy-secondary-to-status-epilepticus-in-a-patient-with-schizophrenia
#18
Elaine Keiko Fujisao, Nathalia Raquel Cristaldo, Aline Marques da Silva Braga, Paulina Rodrigues Cunha, Seizo Yamashita, Luiz Eduardo Betting
A 59-year-old man was admitted with respiratory tract infection, compromised conscience and generalized tonic-clonic seizures. His medical history included schizophrenia diagnosis, for which he had been being treated since he was 27 years old. EEG disclosed non-convulsive status epilepticus. A magnetic resonance image (MRI) acquired 3 days later showed increased left hippocampal volume with hyperintensity on T2-weighted and FLAIR sequences. After being treated with antibiotics and antiepileptic medications, the patient's condition improved...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28213444/the-dendrites-of-ca2-and-ca1-pyramidal-neurons-differentially-regulate-information-flow-in-the-cortico-hippocampal-circuit
#19
Kalyan V Srinivas, Eric W Buss, Qian Sun, Bina Santoro, Hiroto Takahashi, Daniel A Nicholson, Steven A Siegelbaum
The impact of a given neuronal pathway depends on the number of synapses it makes with its postsynaptic target, the strength of each individual synapse and the integrative properties of the postsynaptic dendrites. Here we explore the cellular and synaptic mechanisms responsible for the differential excitatory drive from the entorhinal cortical pathway onto mouse CA2 compared to CA1 pyramidal neurons (PNs). Although both types of neurons receive direct input from entorhinal cortex onto their distal dendrites, these inputs produce a 5-6 fold larger excitatory postsynaptic potential (EPSP) at the soma of CA2 compared to CA1 PNs, which is sufficient to drive action potential output from CA2 but not CA1...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28213441/secreted-metalloproteinase-adamts-3-inactivates-reelin
#20
Himari Ogino, Arisa Hisanaga, Takao Kohno, Yuta Kondo, Kyoko Okumura, Takana Kamei, Tempei Sato, Hiroshi Asahara, Hitomi Tsuiji, Masaki Fukata, Mitsuharu Hattori
The secreted glycoprotein Reelin regulates embryonic brain development and adult brain functions. It has been suggested that reduced Reelin activity contributes to the pathogenesis of several neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer's disease; however, non-invasive methods that can upregulate Reelin activity in vivo have yet to be developed. We previously found that the proteolytic cleavage of Reelin within Reelin repeat 3 (N-t site) abolishes Reelin activity in vitro, but it remains controversial as to whether this effect occurs in vivo Here we partially purified the enzyme that mediates the N-t cleavage of Reelin from the culture supernatant of cerebral cortical neurons...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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