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Schizophrenia CA1

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https://www.readbyqxmd.com/read/29682609/prolonged-cannabidiol-treatment-effects-on-hippocampal-subfield-volumes-in-current-cannabis-users
#1
Camilla Beale, Samantha J Broyd, Yann Chye, Chao Suo, Mark Schira, Peter Galettis, Jennifer H Martin, Murat Yücel, Nadia Solowij
Introduction: Chronic cannabis use is associated with neuroanatomical alterations in the hippocampus. While adverse impacts of cannabis use are generally attributed to Δ9 -tetrahydrocannabinol, emerging naturalistic evidence suggests cannabidiol (CBD) is neuroprotective and may ameliorate brain harms associated with cannabis use, including protection from hippocampal volume loss. This study examined whether prolonged administration of CBD to regular cannabis users within the community could reverse or reduce the characteristic hippocampal harms associated with chronic cannabis use...
2018: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/29566220/neuregulin-1-deficiency-modulates-adolescent-stress-induced-dendritic-spine-loss-in-a-brain-region-specific-manner-and-increases-complement-4-expression-in-the-hippocampus
#2
David J Clarke, Tariq W Chohan, Mustafa S Kassem, Kristie L Smith, Rose Chesworth, Tim Karl, Michael P Kuligowski, Sandra Y Fok, Maxwell R Bennett, Jonathon C Arnold
One neuropathological feature of schizophrenia is a diminished number of dendritic spines in the prefrontal cortex and hippocampus. The neuregulin 1 (Nrg1) system is involved in the plasticity of dendritic spines, and chronic stress decreases dendritic spine densities in the prefrontal cortex and hippocampus. Here, we aimed to assess whether Nrg1 deficiency confers vulnerability to the effects of adolescent stress on dendritic spine plasticity. We also assessed other schizophrenia-relevant neurobiological changes such as microglial cell activation, loss of parvalbumin (PV) interneurons, and induction of complement factor 4 (C4)...
March 16, 2018: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29471549/glutamate-dehydrogenase-deficient-mice-display-schizophrenia-like-behavioral-abnormalities-and-ca1-specific-hippocampal-dysfunction
#3
Sharon S Lander, Usman Khan, Nicole Lewandowski, Darpan Chakraborty, Frank A Provenzano, Susana Mingote, Sergiy Chornyy, Francesca Frigerio, Pierre Maechler, Hanoch Kaphzan, Scott A Small, Stephen Rayport, Inna Gaisler-Salomon
Brain imaging has revealed that the CA1 subregion of the hippocampus is hyperactive in prodromal and diagnosed patients with schizophrenia (SCZ), and that glutamate is a driver of this hyperactivity. Strikingly, mice deficient in the glutamate synthetic enzyme glutaminase have CA1 hypoactivity and a SCZ-resilience profile, implicating glutamate-metabolizing enzymes. To address this further, we examined mice with a brain-wide deficit in the glutamate-metabolizing enzyme glutamate dehydrogenase (GDH), encoded by Glud1, which should lead to glutamate excess due to reduced glutamate metabolism in astrocytes...
February 20, 2018: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29404686/effects-of-haloperidol-and-clozapine-on-synapse-related-gene-expression-in-specific-brain-regions-of-male-rats
#4
Martina von Wilmsdorff, Fabian Manthey, Marie-Luise Bouvier, Oliver Staehlin, Peter Falkai, Eva Meisenzahl-Lechner, Andrea Schmitt, Peter J Gebicke-Haerter
We investigated the effects of clozapine and haloperidol, drugs that are widely used in the treatment of schizophrenia, on gene expression in six cortical and subcortical brain regions of adult rats. Drug treatments started at postnatal day 85 and continued over a 12-week period. Ten animals received haloperidol (1 mg/kg bodyweight) and ten received clozapine (20 mg/kg bodyweight) orally each day. Ten control rats received no drugs. The ten genes selected for this study did not belong to the dopaminergic or serotoninergic systems, which are typically targeted by the two substances, but coded for proteins of the cytoskeleton and proteins belonging to the synaptic transmitter release machinery...
February 5, 2018: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/29359413/effects-of-chronic-ketamine-on-hippocampal-cross-frequency-coupling-implications-for-schizophrenia-pathophysiology
#5
Timothy I Michaels, Lauren L Long, Ian H Stevenson, James J Chrobak, Chi-Ming A Chen
Disrupted neuronal oscillations have been identified as a potentially important biomarker for the perceptual and cognitive symptoms of schizophrenia. Emerging evidences suggest that interactions between different frequency bands, cross-frequency coupling (CFC), serve an important role in integrating sensory and cognitive information and may contribute to disease pathophysiology. In this study, we investigated the effects of 14-day consecutive administration of ketamine (30 mg/kg i.p.) vs. saline on alterations in amplitude and changes in the coupling of low-frequency (0-30 Hz) phase and high-frequency (30-115 Hz) amplitude in the CA1 hippocampus of Long Evans rats...
January 23, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29311665/hippocampal-dysfunction-in-the-pathophysiology-of-schizophrenia-a-selective-review-and-hypothesis-for-early-detection-and-intervention
#6
J A Lieberman, R R Girgis, G Brucato, H Moore, F Provenzano, L Kegeles, D Javitt, J Kantrowitz, M M Wall, C M Corcoran, S A Schobel, S A Small
Scientists have long sought to characterize the pathophysiologic basis of schizophrenia and develop biomarkers that could identify the illness. Extensive postmortem and in vivo neuroimaging research has described the early involvement of the hippocampus in the pathophysiology of schizophrenia. In this context, we have developed a hypothesis that describes the evolution of schizophrenia-from the premorbid through the prodromal stages to syndromal psychosis-and posits dysregulation of glutamate neurotransmission beginning in the CA1 region of the hippocampus as inducing attenuated psychotic symptoms and initiating the transition to syndromal psychosis...
January 9, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29214513/hyper-response-to-novelty-increases-c-fos-expression-in-the-hippocampus-and-prefrontal-cortex-in-a-rat-model-of-schizophrenia
#7
Tomas Monfil, Rubén Antonio Vázquez Roque, Israel Camacho-Abrego, Hiram Tendilla-Beltran, Tommaso Iannitti, Ivan Meneses-Morales, Patricia Aguilar-Alonso, Gonzalo Flores, Julio Cesar Morales-Medina
Schizophrenia is a debilitating disorder that may have a neurodevelopmental origin. For this reason, animal models based on neonatal insults or manipulations have been extensively used to demonstrate schizophrenia-related behaviors. Among those, the neonatal ventral hippocampus lesion (nVHL) is largely used as a model of schizophrenia-related behavior as it mimics behavioral and neurochemical abnormalities often seen in schizophrenic patients including hyperlocomotion in a novel environment. To investigate the neuroanatomical basis of coding novelty in the nVHL rat, we assessed the behavioral locomotor activity paradigm in a novel environment and measured expression of c-Fos, a marker of neural activation, in brain regions involved in the process of coding novelty or locomotion...
February 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29171010/prenatal-exposure-to-ketamine-in-rats-implications-on-animal-models-of-schizophrenia
#8
Carlos M Coronel-Oliveros, Renny Pacheco-Calderón
Schizophrenia is a complex neuropsychiatric disorder characterized by hallucinations, delusions, anhedonia, flat affect and cognitive impairments. The aim of this study was to propose a prenatal treatment with ketamine, a psychedelic drug that acts as a non-competitive inhibitor of glutamate NMDA receptors, as a neurodevelopmental animal model of schizophrenia. The drug was applied (i.m. 60 mg.kg-1  h-1 ) in pregnant Sprague-Dawley rats on gestational Day 14. Offspring behavior was studied on pubertal (4 weeks old) and adult (10 weeks old) stages...
January 2018: Developmental Psychobiology
https://www.readbyqxmd.com/read/29155005/effects-of-genetic-and-environmental-risk-for-schizophrenia-on-hippocampal-activity-and-psychosis-like-behavior-in-mice
#9
Daniel Scott, Carol A Tamminga
Schizophrenia is a serious mental illness most notably characterized by psychotic symptoms. In humans, psychotic disorders are associated with specific hippocampal pathology. However, animal model systems for psychosis often lack this pathology, and have been weak in providing a representation of psychosis. We utilized a double-risk model system combining genetic risk with environmental stress. We hypothesized these factors will induce hippocampal subfield pathology consistent with human findings, as well as behavioral phenotypes relevant to psychosis...
February 26, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29142062/the-serine-protease-inhibitor-neuroserpin-is-required-for-normal-synaptic-plasticity-and-regulates-learning-and-social-behavior
#10
Rebecca Reumann, Ricardo Vierk, Lepu Zhou, Frederice Gries, Vanessa Kraus, Julia Mienert, Eva Romswinkel, Fabio Morellini, Isidre Ferrer, Chiara Nicolini, Margaret Fahnestock, Gabriele Rune, Markus Glatzel, Giovanna Galliciotti
The serine protease inhibitor neuroserpin regulates the activity of tissue-type plasminogen activator (tPA) in the nervous system. Neuroserpin expression is particularly prominent at late stages of neuronal development in most regions of the central nervous system (CNS), whereas it is restricted to regions related to learning and memory in the adult brain. The physiological expression pattern of neuroserpin, its high degree of colocalization with tPA within the CNS, together with its dysregulation in neuropsychiatric disorders, suggest a role in formation and refinement of synapses...
December 2017: Learning & Memory
https://www.readbyqxmd.com/read/28990059/expression-of-nr1-and-apoptosis-levels-in-the-hippocampal-cells-of-mice-treated-with-mk%C3%A2-801
#11
Juan Ding, Hui-Hui Zhou, Quan-Rui Ma, Zhong-Yi He, Jiang-Bo Ma, Yin-Ming Liu, Yi-Wei Zhang, Yu-Qing He, Juan Liu
The aim of the present study was to investigate the characteristics of N‑methyl‑D‑aspartate receptor R1 (NR1) expression and apoptosis in the nerve cells of the hippocampus in schizophrenia‑like mice. C57BL/6 mice were randomly allocated to the following groups: i) Blank group; ii) MK‑801 group; iii) MK‑801+NMDA group, according to body weight. The NMDAR antagonist, MK‑801 (0.6 mg/kg/d) was intraperitoneally injected daily for 14 days to induce a schizophrenia‑like phenotype mouse model, and the effect of the NMDA injection via the lateral ventricle was observed...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28921679/maternal-immune-activation-leads-to-increased-nnos-immunoreactivity-in-the-brain-of-postnatal-day-2-rat-offspring
#12
Jiaxian Zhang, Yu Jing, Hu Zhang, David K Bilkey, Ping Liu
Neuronal nitric oxide synthase (nNOS) is a key arginine metabolising enzyme in the brain, and nNOS-derived nitric oxide (NO) plays an important role in regulating glutamatergic neurotransmission. NO and its related molecules are involved in the pathogenesis of schizophrenia, and human genetic studies have identified schizophrenia risk genes encoding nNOS. This study systematically investigated how maternal immune activation (MIA; a risk factor for schizophrenia) induced by polyinosinic:polycytidylic acid affected nNOS-immunoreactivity in the brain of the resulting male and female offspring at the age of postnatal day (PND) 2...
January 2018: Synapse
https://www.readbyqxmd.com/read/28869582/impaired-hippocampal-place-cell-dynamics-in-a-mouse-model-of-the-22q11-2-deletion
#13
Jeffrey D Zaremba, Anastasia Diamantopoulou, Nathan B Danielson, Andres D Grosmark, Patrick W Kaifosh, John C Bowler, Zhenrui Liao, Fraser T Sparks, Joseph A Gogos, Attila Losonczy
Hippocampal place cells represent the cellular substrate of episodic memory. Place cell ensembles reorganize to support learning but must also maintain stable representations to facilitate memory recall. Despite extensive research, the learning-related role of place cell dynamics in health and disease remains elusive. Using chronic two-photon Ca2+ imaging in hippocampal area CA1 of wild-type and Df(16)A+/- mice, an animal model of 22q11.2 deletion syndrome, one of the most common genetic risk factors for cognitive dysfunction and schizophrenia, we found that goal-oriented learning in wild-type mice was supported by stable spatial maps and robust remapping of place fields toward the goal location...
November 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28842124/phencyclidine-induced-dysregulation-of-primary-cilia-in-the-rodent-brain
#14
Hiroki Shiwaku, Asami Umino, Masakazu Umino, Toru Nishikawa
Significant roles of the primary cilia in the central nervous system have been reported in neural generation and cognitive functions. However, little is known about the possible pathological changes in brain primary cilia in neuropsychiatric disorders. To obtain an insight into the relationship between cilial dysregulation and schizophrenia, we presently investigated the effects of psychotomimetics, phencyclidine, MK-801 (dizocilpine), and methamphetamine, on morphological and molecular indices in the rodent brain...
November 1, 2017: Brain Research
https://www.readbyqxmd.com/read/28838810/the-activation-of-nmda-receptors-alters-the-structural-dynamics-of-the-spines-of-hippocampal-interneurons
#15
Marta Pérez-Rando, Esther Castillo-Gómez, María Bellés, Héctor Carceller, Juan Nácher
N-Methyl-d-Aspartate receptors (NMDARs) are present in both pyramidal neurons and interneurons of the hippocampus. These receptors play a key role in the structural plasticity of excitatory neurons, but to date little is known about their influence on the remodeling of interneurons. Among hippocampal interneurons, the somatostatin expressing cells in the CA1 stratum oriens are of special interest because of their functional importance and structural characteristics: they display dendritic spines, which change their density in response to different stimuli...
September 29, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28809400/prenatal-one-carbon-metabolism-dysregulation-programs-schizophrenia-like-deficits
#16
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...
February 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/28728089/volumetric-and-morphological-characteristics-of-the-hippocampus-are-associated-with-progression-to-schizophrenia-in-patients-with-first-episode-psychosis
#17
R Sauras, A Keymer, A Alonso-Solis, A Díaz, C Molins, F Nuñez, M Rabella, A Roldán, E Grasa, E Alvarez, M J Portella, I Corripio
BACKGROUND: Abnormalities in the hippocampus have been implicated in the pathophysiology of psychosis. However, it is still unclear whether certain abnormalities are a pre-existing vulnerability factor, a sign of disease progression or a consequence of environmental factors. We hypothesized that first-episode psychosis patients who progress to schizophrenia after one year of follow up will display greater volumetric and morphological changes from the very beginning of the disorder. METHODS: We studied the hippocampus of 41 patients with a first-episode psychosis and 41 matched healthy controls...
September 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28505127/variability-of-dna-methylation-within-schizophrenia-risk-loci-across-subregions-of-human-hippocampus
#18
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
#19
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/28433499/changes-in-the-expression-of-metabotropic-glutamate-receptor-5-mglur5-in-a-ketamine-based-animal-model-of-schizophrenia
#20
Dariusz Zurawek, Anna Salerno-Kochan, Marta Dziedzicka-Wasylewska, Agnieszka Nikiforuk, Tomasz Kos, Piotr Popik
It has been shown that the metabotropic glutamate receptor subtype 5 (mGluR5) is functionally associated with the NMDA subtype of the glutamate receptor family (NMDA receptors). These two receptors colocalize in brain regions associated with schizophrenia. Although the role of the NMDA receptor in cognitive and negative symptoms of schizophrenia is well studied, information about the role of mGluR5 receptors in schizophrenia is sparse. In our work, we show that subchronic administration of ketamine, a well-studied, non-competitive antagonist of NMDA receptors, caused cognitive deficits in rats as shown by testing novel object recognition (NOR)...
February 2018: Schizophrenia Research
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