The Experts below are selected from a list of 21507 Experts worldwide ranked by ideXlab platform
Hanna Jaaropeled - One of the best experts on this subject based on the ideXlab platform.
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better understanding of Mechanisms of Schizophrenia and bipolar disorder from human gene expression profiles to mouse models
Neurobiology of Disease, 2012Co-Authors: Chi Ying Lin, Akira Sawa, Hanna JaaropeledAbstract:The molecular Mechanisms of major mental illnesses, such as Schizophrenia and bipolar disorder, are unclear. To address this fundamental question, many groups have studied molecular expression profiles in postmortem brains and other tissues from patients compared with those from normal controls. Development of unbiased high-throughput approaches, such as microarray, RNA-seq, and proteomics, have supported and facilitated this endeavor. In addition to genes directly involved in neuron/glia signaling, especially those encoding for synaptic proteins, genes for metabolic cascades are differentially expressed in the brains of patients with Schizophrenia and bipolar disorder, compared with those from normal controls in DNA microarray studies. Here we propose the importance and usefulness of genetic mouse models in which such differentially expressed molecules are modulated. These animal models allow us to dissect the Mechanisms of how such molecular changes in patient brains may play a role in neuronal circuitries and overall behavioral phenotypes. We also point out that models in which the metabolic genes are modified are obviously untested from mental illness viewpoints, suggesting the potential to re-address these models with behavioral assays and neurochemical assessments.
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neurodevelopmental Mechanisms of Schizophrenia understanding disturbed postnatal brain maturation through neuregulin 1 erbb4 and disc1
Trends in Neurosciences, 2009Co-Authors: Hanna Jaaropeled, Akiko Hayashitakagi, Saurav Seshadri, Atsushi Kamiya, Nicholas J Brandon, Akira SawaAbstract:Schizophrenia (SZ) is primarily an adult psychiatric disorder in which disturbances caused by susceptibility genes and environmental insults during early neurodevelopment initiate neurophysiological changes over a long time course, culminating in the onset of full-blown disease nearly two decades later. Aberrant postnatal brain maturation is an essential mechanism underlying the disease. Currently, symptoms of SZ are treated with anti-psychotic medications that have variable efficacy and severe side effects. There has been much interest in the prodromal phase and the possibility of preventing SZ by interfering with the aberrant postnatal brain maturation associated with this disorder. Thus, it is crucial to understand the Mechanisms that underlie the long-term progression to full disease manifestation to identify the best targets and approaches towards this goal. We believe that studies of certain SZ genetic susceptibility factors with neurodevelopmental implications will be key tools in this task. Accumulating evidence suggests that neuregulin-1 (NRG1) and disrupted-in-Schizophrenia-1 (DISC1) are probably functionally convergent and play key roles in brain development. We provide an update on the role of these emerging concepts in understanding the complex time course of SZ from early neurodevelopmental disturbances to later onset and suggest ways of testing these in the future.
Akira Sawa - One of the best experts on this subject based on the ideXlab platform.
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better understanding of Mechanisms of Schizophrenia and bipolar disorder from human gene expression profiles to mouse models
Neurobiology of Disease, 2012Co-Authors: Chi Ying Lin, Akira Sawa, Hanna JaaropeledAbstract:The molecular Mechanisms of major mental illnesses, such as Schizophrenia and bipolar disorder, are unclear. To address this fundamental question, many groups have studied molecular expression profiles in postmortem brains and other tissues from patients compared with those from normal controls. Development of unbiased high-throughput approaches, such as microarray, RNA-seq, and proteomics, have supported and facilitated this endeavor. In addition to genes directly involved in neuron/glia signaling, especially those encoding for synaptic proteins, genes for metabolic cascades are differentially expressed in the brains of patients with Schizophrenia and bipolar disorder, compared with those from normal controls in DNA microarray studies. Here we propose the importance and usefulness of genetic mouse models in which such differentially expressed molecules are modulated. These animal models allow us to dissect the Mechanisms of how such molecular changes in patient brains may play a role in neuronal circuitries and overall behavioral phenotypes. We also point out that models in which the metabolic genes are modified are obviously untested from mental illness viewpoints, suggesting the potential to re-address these models with behavioral assays and neurochemical assessments.
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neurodevelopmental Mechanisms of Schizophrenia understanding disturbed postnatal brain maturation through neuregulin 1 erbb4 and disc1
Trends in Neurosciences, 2009Co-Authors: Hanna Jaaropeled, Akiko Hayashitakagi, Saurav Seshadri, Atsushi Kamiya, Nicholas J Brandon, Akira SawaAbstract:Schizophrenia (SZ) is primarily an adult psychiatric disorder in which disturbances caused by susceptibility genes and environmental insults during early neurodevelopment initiate neurophysiological changes over a long time course, culminating in the onset of full-blown disease nearly two decades later. Aberrant postnatal brain maturation is an essential mechanism underlying the disease. Currently, symptoms of SZ are treated with anti-psychotic medications that have variable efficacy and severe side effects. There has been much interest in the prodromal phase and the possibility of preventing SZ by interfering with the aberrant postnatal brain maturation associated with this disorder. Thus, it is crucial to understand the Mechanisms that underlie the long-term progression to full disease manifestation to identify the best targets and approaches towards this goal. We believe that studies of certain SZ genetic susceptibility factors with neurodevelopmental implications will be key tools in this task. Accumulating evidence suggests that neuregulin-1 (NRG1) and disrupted-in-Schizophrenia-1 (DISC1) are probably functionally convergent and play key roles in brain development. We provide an update on the role of these emerging concepts in understanding the complex time course of SZ from early neurodevelopmental disturbances to later onset and suggest ways of testing these in the future.
Satoru Otani - One of the best experts on this subject based on the ideXlab platform.
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the effect of non competitive nmda receptor antagonist mk 801 on neuronal activity in rodent prefrontal cortex an animal model for cognitive symptoms of Schizophrenia
Journal of Physiology-paris, 2013Co-Authors: Kevin Blot, Jing Bai, Satoru OtaniAbstract:Schizophrenia affects about 1% of the world population and is a major socio-economical problem in ours societies. Cognitive symptoms are particularly resistant to current treatments and are believed to be closely related to an altered function of prefrontal cortex (PFC). Particularly, abnormalities in the plasticity processes in the PFC are a candidate mechanism underlying cognitive symptoms, and the recent evidences in patients are in line with this hypothesis. Animal pharmacological models of cognitive symptoms, notably with non-competitive NMDA receptor antagonists such as MK-801, are commonly used to investigate the underlying cellular and molecular Mechanisms of Schizophrenia. However, it is still unknown whether in these animal models, impairments in plasticity of PFC neurons are present. In this article, we briefly summarize the current knowledge on the effect of non-competitive NMDA receptor antagonist MK-801 on medial PFC (mPFC) neuronal activity and then introduce a form of plasticity found after acute exposure to MK-801, which was accompanied by cognitive deficits. These observations suggest a potential correlation between cognitive deficits and the aberrant plasticity in the mPFC in the animal model of Schizophrenia.
Toshitaka Nabeshima - One of the best experts on this subject based on the ideXlab platform.
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phencyclidine animal models of Schizophrenia approaches from abnormality of glutamatergic neurotransmission and neurodevelopment
Neurochemistry International, 2007Co-Authors: Akihiro Mouri, Yukihiro Noda, Takeshi Enomoto, Toshitaka NabeshimaAbstract:In humans, phencyclidine (PCP), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, reproduces a Schizophrenia-like psychosis including positive symptoms, negative symptoms and cognitive dysfunction. Thus, the glutamatergic neuronal dysfunction hypothesis is one of the main explanatory hypotheses and PCP-treated animals have been utilized as an animal model of Schizophrenia. The adult rodents treated with PCP repeatedly exhibit hyperlocomotion as an index of positive symptoms, a social behavioral deficit in a social interaction test and enhanced immobility in a forced swimming test as indices of negative symptoms. They also show a sensorimotor gating deficits and cognitive dysfunctions in several learning and memory tests. Some of these behavioral changes endure after withdrawal from repeated PCP treatment. Furthermore, repeated PCP treatment induces some neurochemical and neuroanatomical changes. On the other hand, the exposure to viral or environmental insult in the second trimester of pregnancy increases the probability of subsequently developing Schizophrenia as an adult. NMDA receptor has been implicated in controlling the structure and plasticity of developing brain circuitry. Based on neurodevelopment hypothesis of Schizophrenia, Schizophrenia model rats treated with PCP at the perinatal stage is developed. Perinatal PCP treatment impairs neuronal development and induces long-lasting Schizophrenia-like behaviors in adult period. Many findings suggest that these PCP animal models would be useful for evaluating novel therapeutic candidates and for confirming pathological Mechanisms of Schizophrenia.
Robert H Yolken - One of the best experts on this subject based on the ideXlab platform.
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changes in region and cell type specific expression patterns of neutral amino acid transporter 1 asct 1 in the anterior cingulate cortex and hippocampus in Schizophrenia bipolar disorder and major depression
Journal of Neural Transmission, 2007Co-Authors: Serge Weis, Ida C Llenos, J R Dulay, N Verma, Sarven Sabunciyan, Robert H YolkenAbstract:Although, the pathogenetic Mechanisms of Schizophrenia, bipolar disorder, and major depression are not clearly understood, various neurotransmitter systems are reported to have altered expression patterns of their receptor and transporter proteins. Changes in the expression of the neutral amino acid transporter 1 (ASCT-1) protein in the anterior cingulate gyrus and the hippocampus were investigated using immunohistochemistry and western blotting. A significant decrease in ASCT-1 immunoreactivity in neurons in the cingulate cortex as well as astrocytes of the white matter was seen in Schizophrenia. In bipolar disorder and major depression, similar results were seen for neurons. In the hippocampus, there was a striking loss of immunoreactivity on astrocytes, neurons and interneurons in multiple regions in Schizophrenia and bipolar disorder, while only minor changes were seen in major depression. The altered expression of ASCT-1 in neurons and astrocytes reflects profound changes in glutamatergic neurotransmission and highlights a significant role of astrocytes in the pathophysiology of neurotransmission in these major psychiatric disorders.