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Schizophrenia CA1

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https://www.readbyqxmd.com/read/28302570/hippocampal-endothelin-1-decreases-excitability-of-pyramidal-neurons-and-produces-anxiolytic-effects
#1
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/28214898/early-development-of-parvalbumin-somatostatin-and-cholecystokinin-expressing-neurons-in-rat-brain-following-prenatal-immune-activation-and-maternal-iron-deficiency
#2
Patricia Boksa, Ying Zhang, Dominique Nouel, Alice Wong, Tak Pan Wong
Prenatal maternal infection and maternal iron deficiency during pregnancy are 2 early environmental insults associated with increased risk for schizophrenia in offspring. Substantial evidence suggests that abnormalities in inhibitory γ-aminobutyric acid (GABA) interneuron function, especially in the parvalbumin subtype of GABA interneuron, both developmentally and in adulthood, may contribute mechanistically to cognitive deficits and psychotic symptoms in schizophrenia. This study used a rat model to test whether prenatal immune activation with lipopolysaccharide (LPS; at gestation days, GD, 15 and 16) or maternal iron deficiency (from GD2 to postnatal day P7) or the combination of both insults alters major subtypes of GABAergic interneurons (parvalbumin, somatostatin, cholecystokinin) in brain regions relevant to schizophrenia (medial and dorsolateral prefrontal cortex [PFC], hippocampal CA1 and dentate gyrus, ventral subiculum) in offspring at P14 or P28...
2016: Developmental Neuroscience
https://www.readbyqxmd.com/read/28213444/the-dendrites-of-ca2-and-ca1-pyramidal-neurons-differentially-regulate-information-flow-in-the-cortico-hippocampal-circuit
#3
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/28193301/hippocampal-subregion-volume-changes-associated-with-antipsychotic-treatment-in-first-episode-psychosis
#4
K Rhindress, D G Robinson, J A Gallego, R Wellington, A K Malhotra, P R Szeszko
BACKGROUND: Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis. METHOD: A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial...
February 14, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/28079061/progressive-decline-in-hippocampal-ca1-volume-in-individuals-at-ultra-high-risk-for-psychosis-who-do-not-remit-findings-from-the-longitudinal-youth-at-risk-study
#5
New Fei Ho, Daphne J Holt, Mike Cheung, Juan Eugenio Iglesias, Alex Goh, Mingyuan Wang, Joseph Kw Lim, Joshua de Souza, Joann S Poh, Yuen Mei See, Alison R Adcock, Stephen J Wood, Michael Wl Chee, Jimmy Lee, Juan Zhou
Most individuals identified as ultra-high-risk (UHR) for psychosis do not develop frank psychosis. They continue to exhibit subthreshold symptoms, or go on to fully remit. Prior work has shown that the volume of CA1, a subfield of the hippocampus, is selectively reduced in the early stages of schizophrenia. Here we aimed to determine whether patterns of volume change of CA1 are different in UHR individuals who do or do not achieve symptomatic remission. Structural MRI scans were acquired at baseline and at 1-2 follow-up time points (at 12-month intervals) from 147 UHR and healthy control subjects...
February 1, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28059046/long-term-effects-of-aripiprazole-exposure-on-monoaminergic-and-glutamatergic-receptor-subtypes-comparison-with-cariprazine
#6
Yong Kee Choi, Nika Adham, Béla Kiss, István Gyertyán, Frank I Tarazi
OBJECTIVE: This study examined the chronic effects of aripiprazole and cariprazine on serotonin (5-HT1A and 5-HT2A) and glutamate (NMDA and AMPA) receptor subtypes. In addition, the effects of aripiprazole on D2 and D3 receptors were tested and compared with previously reported cariprazine data. METHODS: Rats received vehicle, aripiprazole (2, 5, or 15 mg/kg), or cariprazine (0.06, 0.2, or 0.6 mg/kg) for 28 days. Receptor levels were quantified using autoradiographic assays on brain sections from the medial prefrontal cortex (MPC), dorsolateral frontal cortex (DFC), nucleus accumbens (NAc), caudate-putamen medial (CPu-M), caudate-putamen lateral (CPu-L), hippocampal CA1 (HIPP-CA1) and CA3 (HIPP-CA3) regions, and the entorhinal cortex (EC)...
January 6, 2017: CNS Spectrums
https://www.readbyqxmd.com/read/27911756/activation-of-group-ii-metabotropic-glutamate-receptors-promotes-ltp-induction-at-schaffer-collateral-ca1-pyramidal-cell-synapses-by-priming-nmda-receptors
#7
Nadia Rosenberg, Urs Gerber, Jeanne Ster
It is well established that selective activation of group I metabotropic glutamate (mGlu) receptors induces LTD of synaptic transmission at Schaffer collateral-CA1 synapses. In contrast, application of 1S,3R-ACPD, a mixed agonist at group I and group II mGlu receptors, induces LTP. Using whole-cell recordings from CA1 pyramidal cells and field recordings in the hippocampal CA1 region, we investigated the specific contribution of group II mGlu receptors to synaptic plasticity at Schaffer collateral-CA1 synapses in acute slices of adult mice...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27897969/satb2-determines-mirna-expression-and-long-term-memory-in-the-adult-central-nervous-system
#8
Clemens Jaitner, Chethan Reddy, Andreas Abentung, Nigel Whittle, Dietmar Rieder, Andrea Delekate, Martin Korte, Gaurav Jain, Andre Fischer, Farahnaz Sananbenesi, Isabella Cera, Nicolas Singewald, Georg Dechant, Galina Apostolova
SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory...
November 29, 2016: ELife
https://www.readbyqxmd.com/read/27866902/the-atypical-antipsychotic-olanzapine-disturbs-depotentiation-by-modulating-machrs-and-impairs-reversal-learning
#9
Woo Seok Song, Jin Hee Cha, Sang Ho Yoon, Young Seon Cho, Kyeong-Yeol Park, Myoung-Hwan Kim
Antipsychotic medication is an essential component for treating schizophrenia, which is a serious mental disorder that affects approximately 1% of the global population. Olanzapine (Olz), one of the most frequently prescribed atypical antipsychotics, is generally considered a first-line drug for treating schizophrenia. In contrast to psychotic symptoms, the effects of Olz on cognitive symptoms of schizophrenia are still unclear. In addition, the mechanisms by which Olz affects the neural circuits associated with cognitive function are unknown...
March 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27833555/ginkgolic-acid-protects-against-a%C3%AE-induced-synaptic-dysfunction-in-the-hippocampus
#10
Dalila Mango, Filippo Weisz, Robert Nisticò
Ginkgo leaf is the most used form of supplement for cognitive ailments. The standardized extract formulation EGb 761 is a dietary supplement with proven benefit in several neurological and psychiatric conditions including memory decline in Alzheimer's disease, schizophrenia and dementia. Ginkgolic acid (GA) is a component of this extract which shows pleiotropic effects including antitumoral and anti-HIV action; however, its effect on memory is still unknown. Here, we carried out an electrophysiological analysis to investigate the effects of GA on long term potentiation and synaptic transmission at CA1 hippocampal synapses...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27824119/intake-of-7-8-dihydroxyflavone-during-juvenile-and-adolescent-stages-prevents-onset-of-psychosis-in-adult-offspring-after-maternal-immune-activation
#11
Mei Han, Ji-Chun Zhang, Wei Yao, Chun Yang, Tamaki Ishima, Qian Ren, Min Ma, Chao Dong, Xu-Feng Huang, Kenji Hashimoto
Prenatal infection and subsequent abnormal neurodevelopment of offspring is involved in the etiology of schizophrenia. Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, tropomyosin receptor kinase B (TrkB) signaling plays a key role in the neurodevelopment. Pregnant mice exposed to polyriboinosinic-polyribocytidylic acid [poly(I:C)] causes schizophrenia-like behavioral abnormalities in their offspring at adulthood. Here we found that the juvenile offspring of poly(I:C)-treated mice showed cognitive deficits, as well as reduced BDNF-TrkB signaling in the prefrontal cortex (PFC)...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27806441/acute-systemic-mk-801-induced-functional-uncoupling-between-hippocampal-areas-ca3-and-ca1-with-distant-effect-in-the-retrosplenial-cortex
#12
Helena Buchtová, Iveta Fajnerová, Aleš Stuchlík, Štěpán Kubík
The hippocampus and retrosplenial cortex are integrated within a higher-order cognitive circuit supporting relational (spatial, contextual, episodic) forms of learning and memory. Hippocampal place cells can coordinate multiple parallel representations in the same physical environment. Novel environment exploration triggers expression of immediate-early genes (IEGs) Arc and Homer1a in spatial context-specific ensembles of CA1 and CA3 neurons. Less is know about ensemble coding in the retrosplenial cortex (RSC), a region directly connected and functionally coupled to CA1...
November 2, 2016: Hippocampus
https://www.readbyqxmd.com/read/27784625/nicotine-induced-neuroplasticity-counteracts-the-effect-of-schizophrenia-linked-neuregulin-1-signaling-on-nmdar-function-in-the-rat-hippocampus
#13
Yoshihiko Yamazaki, Katumi Sumikawa
A high rate of heavy tobacco smoking among people with schizophrenia has been suggested to reflect self-medication and amelioration of cognitive dysfunction, a core feature of schizophrenia. NMDAR hypofunction is hypothesized to be a mechanism of cognitive dysfunction, and excessive schizophrenia-linked neuregulin 1 (NRG1) signaling through its receptor ErbB4 can suppress NMDAR function by preventing Src-mediated enhancement of NMDAR responses. Here we investigated whether chronic nicotine exposure in rats by subcutaneous injection of nicotine (0...
February 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27729083/disrupted-in-schizophrenia1-disc1-l100p-mutation-alters-synaptic-transmission-and-plasticity-in-the-hippocampus-and-causes-recognition-memory-deficits
#14
Lin Cui, Wei Sun, Ming Yu, Nan Li, Li Guo, Huating Gu, Yu Zhou
Disrupted-in-schizophrenia 1(DISC1) is a promising candidate susceptibility gene for a spectrum of psychiatric illnesses that share cognitive impairments in common, including schizophrenia, bipolar disorder and major depression. Here we report that DISC1 L100P homozygous mutant shows normal anxiety- and depression-like behavior, but impaired object recognition which is prevented by administration of atypical antipsychotic drug clozapine. Ca(2+) image analysis reveals suppression of glutamate-evoked elevation of cytoplasmic [Ca(2+)] in L100P hippocampal slices...
October 12, 2016: Molecular Brain
https://www.readbyqxmd.com/read/27562725/bacopa-monnieri-brahmi-improved-novel-object-recognition-task-and-increased-cerebral-vesicular-glutamate-transporter-type-3-in-sub-chronic-phencyclidine-rat-model-of-schizophrenia
#15
Pritsana Piyabhan, Supaporn Wannasiri, Jarinyaporn Naowaboot
Reduced vesicular glutamate transporter 1 (VGLUT1) and 2 (VGLUT2) indicate glutamatergic hypofunction leading to cognitive impairment in schizophrenia. However, VGLUT3 involvement in cognitive dysfunction has not been reported in schizophrenia. Brahmi (Bacopa monnieri) might be a new treatment and prevention for cognitive deficits in schizophrenia by acting on cerebral VGLUT3 density. We aimed to study cognitive enhancement- and neuroprotective-effects of Brahmi on novel object recognition and cerebral VGLUT3 immunodensity in sub-chronic (2 mg/kg, Bid, ip) phencyclidine (PCP) rat model of schizophrenia...
December 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27535377/developmental-restoration-of-ltp-deficits-in-heterozygous-camkii%C3%AE-ko-mice
#16
Dayton J Goodell, Tim A Benke, K Ulrich Bayer
The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory and cognition. The heterozygous CaMKIIα isoform KO (CaMKIIα(+/-)) mice have a schizophrenia-related phenotype, including impaired working memory. Here, we examined synaptic strength and plasticity in two brain areas implicated in working memory, hippocampus CA1 and medial prefrontal cortex (mPFC). Young CaMKIIα(+/-) mice (postnatal days 12-16; corresponding to a developmental stage well before schizophrenia manifestation in humans) showed impaired hippocampal CA1 LTP...
November 1, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27507650/long-term-potentiation-modulates-synaptic-phosphorylation-networks-and-reshapes-the-structure-of-the-postsynaptic-interactome
#17
Jing Li, Brent Wilkinson, Veronica A Clementel, Junjie Hou, Thomas J O'Dell, Marcelo P Coba
The postsynaptic site of neurons is composed of more than 1500 proteins arranged in protein-protein interaction complexes, the composition of which is modulated by protein phosphorylation through the actions of complex signaling networks. Components of these networks function as key regulators of synaptic plasticity, in particular hippocampal long-term potentiation (LTP). The postsynaptic density (PSD) is a complex multicomponent structure that includes receptors, enzymes, scaffold proteins, and structural proteins...
2016: Science Signaling
https://www.readbyqxmd.com/read/27476436/acute-phencyclidine-administration-induces-c-fos-immunoreactivity-in-interneurons-in-cortical-and-subcortical-regions
#18
Mona E Hervig, Morten S Thomsen, Imre Kalló, Jens D Mikkelsen
Dysfunction of N-Methyl-d-aspartate receptors (NMDARs) is believed to underlie some of the symptoms in schizophrenia, and non-competitive NMDAR antagonists (including phencyclidine (PCP)) are widely used as pharmacological schizophrenia models. Furthermore, mounting evidence suggests that impaired γ-aminobutyric acid (GABA) neurotransmission contributes to the cognitive deficits in schizophrenia. Thus alterations in GABAergic interneurons have been observed in schizophrenia patients and animal models. Acute systemic administration of PCP increases levels of c-Fos in several cortical and subcortical areas, but whether such induction occurs in specific populations of GABAergic interneuron subtypes still remains to be established...
July 29, 2016: Neuroscience
https://www.readbyqxmd.com/read/27430010/molecular-evidence-of-synaptic-pathology-in-the-ca1-region-in-schizophrenia
#19
Natalie Matosin, Francesca Fernandez-Enright, Jeremy S Lum, Martin Engel, Jessica L Andrews, Nils C Gassen, Klaus V Wagner, Mathias V Schmidt, Kelly A Newell
Alterations of postsynaptic density (PSD)95-complex proteins in schizophrenia ostensibly induce deficits in synaptic plasticity, the molecular process underlying cognitive functions. Although some PSD95-complex proteins have been previously examined in the hippocampus in schizophrenia, the status of other equally important molecules is unclear. This is especially true in the cornu ammonis (CA)1 hippocampal subfield, a region that is critically involved in the pathophysiology of the illness. We thus performed a quantitative immunoblot experiment to examine PSD95 and several of its associated proteins in the CA1 region, using post mortem brain samples derived from schizophrenia subjects with age-, sex-, and post mortem interval-matched controls (n=20/group)...
2016: NPJ Schizophrenia
https://www.readbyqxmd.com/read/27421225/the-pathogenic-mechanism-of-dysbindin-1b-toxic-aggregation-bloc-1-and-intercellular-vesicle-trafficking
#20
Wei Yang, Chunyan Zhu, Yan Shen, Qi Xu
DTNBP1, which encodes dysbindin-1, is associated with cognitive impairment. Genetic evidence indicates that the C allele of rs117610176 leads to an increase in DTNBP-1b mRNA splicing in patients with paranoid schizophrenia. In addition, dysbindin-1B, rather than dysbindin-1A/C, exhibits a tendency toward toxic aggregation. In postmortem brains, dysbindin-1B not only aggregates with itself, it also co-aggregates with proteins that interact with it. However, the pathogenic mechanism underlying dysbindin-1B toxic aggregation remains unknown...
October 1, 2016: Neuroscience
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