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Schizophrenia Hippocampus

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https://www.readbyqxmd.com/read/29471549/glutamate-dehydrogenase-deficient-mice-display-schizophrenia-like-behavioral-abnormalities-and-ca1-specific-hippocampal-dysfunction
#1
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/29467681/glutamate-levels-and-resting-cerebral-blood-flow-in-anterior-cingulate-cortex-are-associated-at-rest-and-immediately-following-infusion-of-s-ketamine-in-healthy-volunteers
#2
Kirsten Borup Bojesen, Kasper Aagaard Andersen, Sophie Nordahl Rasmussen, Lone Baandrup, Line Malmer Madsen, Birte Yding Glenthøj, Egill Rostrup, Brian Villumsen Broberg
Progressive loss of brain tissue is seen in some patients with schizophrenia and might be caused by increased levels of glutamate and resting cerebral blood flow (rCBF) alterations. Animal studies suggest that the normalisation of glutamate levels decreases rCBF and prevents structural changes in hippocampus. However, the relationship between glutamate and rCBF in anterior cingulate cortex (ACC) of humans has not been studied in the absence of antipsychotics and illness chronicity. Ketamine is a noncompetitive N -methyl-D-aspartate receptor antagonist that transiently induces schizophrenia-like symptoms and neurobiological disturbances in healthy volunteers (HVs)...
2018: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29467679/the-endocannabinoid-system-across-postnatal-development-in-transmembrane-domain-neuregulin-1-mutant-mice
#3
Rose Chesworth, Leonora E Long, Cynthia Shannon Weickert, Tim Karl
The use of cannabis is a well-established component risk factor for schizophrenia, particularly in adolescent individuals with genetic predisposition for the disorder. Alterations to the endocannabinoid system have been found in the prefrontal cortex of patients with schizophrenia. Thus, we assessed whether molecular alterations exist in the endocannabinoid signalling pathway during brain development in a mouse model for the schizophrenia risk gene neuregulin 1 ( Nrg1 ). We analysed transcripts encoding key molecules of the endocannabinoid system in heterozygous transmembrane domain Nrg1 mutant mice ( Nrg1 TM HET), which is known to have increased sensitivity to cannabis exposure...
2018: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29444252/human-striatal-response-to-reward-anticipation-linked-to-hippocampal-glutamate-levels
#4
Matthijs G Bossong, Robin Wilson, Elizabeth Appiah-Kusi, Philip McGuire, Sagnik Bhattacharyya
Background: Dysfunctional reward processing is associated with a number of psychiatric disorders, such as addiction and schizophrenia. It is thought that reward is regulated mainly by dopamine transmission in the ventral striatum. Contemporary animal models suggest that striatal dopamine concentrations and associated behaviours are related to glutamatergic functioning in the ventral hippocampus. However, in humans the association between reward-related ventral striatal response and hippocampal glutamate levels is unclear...
February 10, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29440309/the-phosphodiesterase-2a-inhibitor-tak-915-ameliorates-cognitive-impairments-and-social-withdrawal-in-n-methyl-d-aspartate-receptor-antagonist-induced-rat-models-of-schizophrenia
#5
Masato Nakashima, Haruka Imada, Eri Shiraishi, Yuki Ito, Noriko Suzuki, Maki Miyamoto, Takahiko Taniguchi, Hiroki Iwashita
The pathophysiology of schizophrenia has been associated with glutamatergic dysfunction. Modulation of the glutamatergic signaling pathway, including N-methyl-D-aspartate (NMDA) receptors, can provide a new therapeutic target for schizophrenia. Phosphodiesterase 2A (PDE2A) is highly expressed in the forebrain, and is a dual substrate enzyme that hydrolyzes both cAMP and cGMP, which play pivotal roles as intracellular second messengers downstream of NMDA receptors. Here we characterize the in vivo pharmacological profile of a selective and brain penetrant PDE2A inhibitor, (N-{(1S)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide) (TAK-915) as a novel treatment for schizophrenia...
February 13, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29430617/estrogen-receptor-%C3%AE-agonist-attenuates-endoplasmic-reticulum-stress-induced-changes-in-social-behavior-and-brain-connectivity-in-mice
#6
Amanda Crider, Tyler Nelson, Talisha Davis, Kiley Fagan, Kumar Vaibhav, Matthew Luo, Sunay Kamalasanan, Alvin V Terry, Anilkumar Pillai
Impaired social interaction is a key feature of several major psychiatric disorders including depression, autism, and schizophrenia. While, anatomically, the prefrontal cortex (PFC) is known as a key regulator of social behavior, little is known about the cellular mechanisms that underlie impairments of social interaction. One etiological mechanism implicated in the pathophysiology of the aforementioned psychiatric disorders is cellular stress and consequent adaptive responses in the endoplasmic reticulum (ER) that can result from a variety of environmental and physical factors...
February 12, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29407214/impaired-glucocorticoid-mediated-hpa-axis-negative-feedback-induced-by-juvenile-social-isolation-in-male-rats
#7
Giorgia Boero, Maria Giuseppina Pisu, Francesca Biggio, Laura Muredda, Gianfranca Carta, Sebastiano Banni, Elena Paci, Paolo Follesa, Alessandra Concas, Patrizia Porcu, Mariangela Serra
We previously demonstrated that socially isolated rats at weaning showed a significant decrease in corticosterone and adrenocorticotropic hormone (ACTH) levels, associated with an enhanced response to acute stressful stimuli. Here we shown that social isolation decreased levels of total corticosterone and of its carrier corticosteroid-binding globulin, but did not influence the availability of the free active fraction of corticosterone, both under basal conditions and after acute stress exposure. Under basal conditions, social isolation increased the abundance of glucocorticoid receptors, while it decreased that of mineralocorticoid receptors...
January 31, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29406270/early-life-photoperiod-influences-depression-like-behavior-prepulse-inhibition-of-the-acoustic-startle-response-and-hippocampal-astrogenesis-in-mice
#8
Yusuke Takai, Misato Kawai, Tadashi Ogo, Takashi Ichinose, Shigeki Furuya, Nozomu Takaki, Yukihiro Tone, Hiroshi Udo, Mitsuhiro Furuse, Shinobu Yasuo
Environmental factors during early life stages affect behavioral and physiological phenotypes in adulthood. We examined the effect of photoperiods during development on neurogenesis and affective behaviors during adolescence/adulthood using C57BL/6J mice. Mice were born and raised until weaning under long-day conditions (LDs) or short-day conditions (SDs), followed by a 12L12D cycle until adulthood. Adult mice born under SD showed a shorter latency to first immobility in the forced swim test when compared with the mice born under LD...
February 3, 2018: Neuroscience
https://www.readbyqxmd.com/read/29391571/dietary-glucoraphanin-prevents-the-onset-of-psychosis-in-the-adult-offspring-after-maternal-immune-activation
#9
Akiko Matsuura, Tamaki Ishima, Yuko Fujita, Yoshimi Iwayama, Shunsuke Hasegawa, Ryouka Kawahara-Miki, Motoko Maekawa, Manabu Toyoshima, Yusuke Ushida, Hiroyuki Suganuma, Satoshi Kida, Takeo Yoshikawa, Masaomi Iyo, Kenji Hashimoto
Maternal immune activation (MIA) contributes to behavioral abnormalities relevant to schizophrenia in adult offspring, although the molecular mechanisms underlying MIA-induced behavioral changes remain unclear. Here we demonstrated that dietary intake of glucoraphanin (GF), the precursor of a natural antioxidant sulforaphane, during juvenile and adolescent stages prevented cognitive deficits and loss of parvalbumin (PV) immunoreactivity in the medial prefrontal cortex (mPFC) of adult offspring after MIA. Gene set enrichment analysis by RNA sequencing showed that MIA caused abnormal expression of centrosome-related genes in the PFC and hippocampus of adult offspring, and that dietary intake of GF improved these abnormal gene expressions...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29391390/ulk4-regulates-gabaergic-signaling-and-anxiety-related-behavior
#10
Min Liu, Marie Fitzgibbon, Yanqin Wang, Jamie Reilly, Xiaohong Qian, Timothy O'Brien, Steve Clapcote, Sanbing Shen, Michelle Roche
Excitation/inhibition imbalance has been proposed as a fundamental mechanism in the pathogenesis of neuropsychiatric and neurodevelopmental disorders, in which copy number variations of the Unc-51 like kinase 4 (ULK4) gene encoding a putative Serine/Threonine kinase have been reported in approximately 1/1000 of patients suffering pleiotropic clinical conditions of schizophrenia, depression, autistic spectrum disorder (ASD), developmental delay, language delay, intellectual disability, or behavioral disorder...
February 2, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29385549/the-circuitry-of-dopamine-system-regulation-and-its-disruption-in-schizophrenia-insights-into-treatment-and-prevention
#11
Anthony A Grace, Felipe V Gomes
Despite evidence for a role of the dopamine system in the pathophysiology of schizophrenia, there has not been substantial evidence that this disorder originates from a pathological change within the dopamine system itself. Current data from human imaging studies and preclinical investigations instead point to a disruption in afferent regulation of the dopamine system, with a focus on the hippocampus. We found that the hippocampus in the methylazoxymethanol acetate (MAM) rodent developmental disruption model of schizophrenia is hyperactive and dysrhythmic, possibly due to loss of parvalbumin interneurons, leading to a hyperresponsive dopamine system...
January 29, 2018: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29375819/inhibitory-control-of-the-excitatory-inhibitory-balance-in-psychiatric-disorders
#12
REVIEW
Martijn Selten, Hans van Bokhoven, Nael Nadif Kasri
Neuronal networks consist of different types of neurons that all play their own role in order to maintain proper network function. The two main types of neurons segregate in excitatory and inhibitory neurons, which together regulate the flow of information through the network. It has been proposed that changes in the relative strength in these two opposing forces underlie the symptoms observed in psychiatric disorders, including autism and schizophrenia. Here, we review the role of alterations to the function of the inhibitory system as a cause of psychiatric disorders...
2018: F1000Research
https://www.readbyqxmd.com/read/29362511/neuropsychiatric-phenotypes-produced-by-gaba-reduction-in-mouse-cortex-and-hippocampus
#13
Stefan M Kolata, Kazuhito Nakao, Vivek Jeevakumar, Emily L Farmer-Alroth, Yuko Fujita, Aundrea F Bartley, Sunny Zhihong Jiang, Gregory R Rompala, Robert E Sorge, Dennisse V Jimenez, Keri Martinowich, Yolanda Mateo, Kenji Hashimoto, Lynn E Dobrunz, Kazu Nakazawa
Whereas cortical GAD67 reduction and subsequent GABA level decrease are consistently observed in schizophrenia and depression, it remains unclear how these GABAergic abnormalities contribute to specific symptoms. We modeled cortical GAD67 reduction in mice, in which the Gad1 gene is genetically ablated from ~50% of cortical and hippocampal interneurons. Mutant mice showed a reduction of tissue GABA in the hippocampus and cortex including mPFC, and exhibited a cluster of effort-based behavior deficits including decreased home-cage wheel running and increased immobility in both tail suspension and forced swim tests...
December 6, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29359413/effects-of-chronic-ketamine-on-hippocampal-cross-frequency-coupling-implications-for-schizophrenia-pathophysiology
#14
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 the present study, we investigated the effects of 14-day consecutive administration of ketamine (30 mg/kg i.p.) versus 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/29357198/inactivation-of-nucleus-reuniens-impairs-spatial-working-memory-and-behavioral-flexibility-in-the-rat
#15
Tatiana D Viena, Stephanie B Linley, Robert P Vertes
The hippocampal formation (HF) and medial prefrontal cortex (mPFC) play critical roles in spatial working memory (SWM). The nucleus reuniens (RE) of the ventral midline thalamus is an important anatomical link between the HF and mPFC, and as such is crucially involved SWM functions that recruit both structures. Little is known, however, regarding the role of RE in other behaviors mediated by this circuit. In the present study, we examined the role of RE in spatial working memory and executive functioning following reversible inactivation of RE with either muscimol or procaine...
January 22, 2018: Hippocampus
https://www.readbyqxmd.com/read/29352126/role-of-subcortical-structures-on-cognitive-and-social-function-in-schizophrenia
#16
Daisuke Koshiyama, Masaki Fukunaga, Naohiro Okada, Fumio Yamashita, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Kazutaka Ohi, Haruo Fujino, Yoshiyuki Watanabe, Kiyoto Kasai, Ryota Hashimoto
Subcortical regions have a pivotal role in cognitive, affective, and social functions in humans, and the structural and functional abnormalities of the regions have been associated with various psychiatric disorders. Although previous studies focused on the neurocognitive and socio-functional consequences of prefrontal and tempolo-limbic abnormalities in psychiatric disorders, those of subcortical structures remain largely unknown. Recently, MRI volume alterations in subcortical structures in patients with schizophrenia have been replicated in large-scale meta-analytic studies...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29332270/correction-to-hyper-response-to-novelty-increases-c-fos-expression-in-the-hippocampus-and-prefrontal-cortex-in-a-rat-model-of-schizophrenia
#17
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
The original version of this article unfortunately contained a mistake. The spelling of the author Tommaso Ianniti was incorrect and has been corrected as Tommaso Iannitti. The original article has been corrected.
January 13, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29329382/adolescent-synthetic-cannabinoid-exposure-produces-enduring-changes-in-dopamine-neuron-activity-in-a-rodent-model-of-schizophrenia-susceptibility
#18
David D Aguilar, Andrea Giuffrida, Daniel J Lodge
Background: Epidemiological studies recognize cannabis intake as a risk factor for schizophrenia, yet the majority of adolescents who use marijuana do not develop psychosis. Similarly, the abuse of synthetic cannabinoids poses a risk for psychosis. For these reasons, it is imperative to understand the effects of adolescent cannabinoid exposure in susceptible individuals. Method: We have recently developed a novel rodent model of schizophrenia susceptibility, the F2 MAM rat, where only a proportion (~40%) of rats display a schizophrenia-like phenotype...
January 10, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29326362/-18f-pbr111-pet-imaging-in-healthy-controls-and-schizophrenia-test-retest-reproducibility-and-quantification-of-neuroinflammation
#19
Julie Ottoy, Livia De Picker, Jeroen Verhaeghe, Steven Deleye, Leonie Wyffels, Lauren Kosten, Bernard Sabbe, Violette Coppens, Maarten Timmers, Luc Van Nueten, Sarah Ceyssens, Sigrid Stroobants, Manuel Morrens, Steven Staelens
Activated microglia express the translocator protein (TSPO) on the outer mitochondrial membrane. 18F-PBR111 is a second-generation positron emission tomography (PET) ligand that specifically binds the TSPO, allowing in-vivo visualization and quantification of neuroinflammation. The aim of this study is to evaluate if the test-retest variability of 18F-PBR111 in healthy controls is acceptable to detect a psychosis-associated neuroinflammatory signal in schizophrenia. Methods: Dynamic 90-min 18F-PBR111 scans were obtained in 17 healthy male controls (HC) and 11 male schizophrenia patients during a psychotic episode (SP)...
January 11, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29317603/subcortical-association-with-memory-performance-in-schizophrenia-a-structural-magnetic-resonance-imaging-study
#20
Daisuke Koshiyama, Masaki Fukunaga, Naohiro Okada, Fumio Yamashita, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Kazutaka Ohi, Haruo Fujino, Yoshiyuki Watanabe, Kiyoto Kasai, Ryota Hashimoto
Memory performance is severely impaired in individuals with schizophrenia. Although several studies have reported a relationship between memory performance and hippocampal volume, only a few structural magnetic resonance imaging (MRI) studies have investigated the relationship between memory performance and subcortical structures other than hippocampus in patients with schizophrenia. We investigated the relationship between memory performance and subcortical regional volumes in a large sample of patients with schizophrenia...
January 10, 2018: Translational Psychiatry
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