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      Expression of vasopressin mRNA in the hypothalamus of individuals with a diagnosis of schizophrenia

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          Abstract

          Objective

          This study investigates the expression of mRNA encoding vasopressin in the hypothalamus of autopsy brains of individuals diagnosed with schizophrenia.

          Methods

          Ten brains of individuals with schizophrenia and 10 brains from individuals without any disease were examined during autopsy. The hypothalamic block was dissected and immersion fixed in paraformaldehyde, sucrose substituted, frozen, and cut into 20‐µm‐thick coronal cryostat sections. The sections were hybridized with an S‐35‐labeled DNA antisense oligo probe and after washing covered by an X‐ray film. The hybridization signals on the films were transferred to a computer and densitometrically quantified.

          Results

          The densitometry signals showed a statistically significant lower mRNA expression (53% decrease; p = 0.014) in the paraventricular nucleus of the individuals with schizophrenia compared to the controls. In the supraoptic nucleus, the decrease in the group with schizophrenia was 39% compared to the controls, but this decrease was not statistically significant ( p = 0.194).

          Conclusions

          Our results show a low expression of mRNA encoding vasopressin in the paraventricular nucleus of the individuals with schizophrenia. We suggest that vasopressin is not directly involved in the pathogenesis of schizophrenia, but might influence schizophrenic symptoms via vasopressin receptors located in the social behavioral neural network in the forebrain.

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          Most cited references41

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          Oxytocin, vasopressin, and the neurogenetics of sociality.

          There is growing evidence that the neuropeptides oxytocin and vasopressin modulate complex social behavior and social cognition. These ancient neuropeptides display a marked conservation in gene structure and expression, yet diversity in the genetic regulation of their receptors seems to underlie natural variation in social behavior, both between and within species. Human studies are beginning to explore the roles of these neuropeptides in social cognition and behavior and suggest that variation in the genes encoding their receptors may contribute to variation in human social behavior by altering brain function. Understanding the neurobiology and neurogenetics of social cognition and behavior has important implications, both clinically and for society.
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            Genetic insights into the neurodevelopmental origins of schizophrenia

            Schizophrenia is a severe neuropsychiatric disorder with a longstanding history of neurobiological investigation. Although the underlying causal mechanisms remain unknown, early neurodevelopmental events have been implicated in pathogenesis, initially by epidemiological and circumstantial data but more recently by brain-specific molecular and genetic findings. Notably, genomic research has recently uncovered discrete risk variants and risk loci associated with schizophrenia, with the potential to elucidate disease mechanisms. This Review revisits the neurodevelopmental model of schizophrenia from a current genetics perspective, delineating the complex genetic basis of the disorder and highlighting gene expression and epigenetic analyses of post-mortem cortical tissue that suggest that early brain development mediates genetic risk associated with schizophrenia. Future functional genomics investigations will accordingly need to characterize schizophrenia risk loci in relevant neurodevelopmental models.
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              Human postmortem tissue: what quality markers matter?

              Postmortem human brain tissue is used for the study of many different brain diseases. A key factor in conducting postmortem research is the quality of the tissue. Unlike animal tissue, whose condition at death can be controlled and influenced, human tissue can only be collected naturalistically. This introduces potential confounds, based both on pre- and postmortem conditions, that may influence the quality of tissue and its ability to yield accurate results. The traditionally recognized confounds that reduce tissue quality are agonal factors (e.g., coma, hypoxia, hyperpyrexia at the time of death), and long postmortem interval (PMI). We measured tissue quality parameters in over 100 postmortem cases collected from different sources and correlated them with RNA quality (as indicated by the RNA Integrity Number (RIN)) and with protein quality (as measured by the level of representative proteins). Our results show that the most sensible indicator of tissue quality is RIN and that there is a good correlation between RIN and the pH. No correlation developed between protein levels and the aforementioned factors. Moreover, even when RNA was degraded, the protein levels remained stable. However, these correlations did not prove true under all circumstances (e.g., thawed tissue, surgical tissue), that yielded unexpected quality indicators. These data also suggest that cases whose source was a Medical Examiner's office represent high tissue quality.
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                Author and article information

                Contributors
                morm@sund.ku.dk
                Journal
                Brain Behav
                Brain Behav
                10.1002/(ISSN)2157-9032
                BRB3
                Brain and Behavior
                John Wiley and Sons Inc. (Hoboken )
                2162-3279
                13 July 2019
                September 2019
                : 9
                : 9 ( doiID: 10.1002/brb3.v9.9 )
                : e01355
                Affiliations
                [ 1 ] Department of Forensic Medicine, Section of Forensic Pathology, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark
                [ 2 ] Faculty of Health and Medical Sciences, Department of Neuroscience University of Copenhagen Copenhagen Denmark
                Author notes
                [*] [* ] Correspondence

                Morten Møller, Department of Neuroscience, University of Copenhagen, Panum Institute 24.6.04, Blegdamsvej 3, 2200 Copenhagen, Denmark.

                Email: morm@ 123456sund.ku.dk

                Author information
                https://orcid.org/0000-0002-3263-7482
                Article
                BRB31355
                10.1002/brb3.1355
                6749484
                31339235
                8018a878-9219-476b-bd9a-8294149847be
                © 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 08 January 2019
                : 30 April 2019
                : 01 May 2019
                Page count
                Figures: 4, Tables: 1, Pages: 8, Words: 5827
                Funding
                Funded by: SURVIVE project, Dept. Forensic Medicine, University of Copenhagen
                Award ID: UND-2016-16
                Funded by: A.P.Møller foundation for the Advancement of Medical Science
                Award ID: gr.nr. 16-249
                Funded by: Augustinus Foundation
                Award ID: gr.nr.16-4611
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                brb31355
                September 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.9 mode:remove_FC converted:18.09.2019

                Neurosciences
                mrna,paraventricular,schizophrenia,vasopressin
                Neurosciences
                mrna, paraventricular, schizophrenia, vasopressin

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