The origin of NMDA receptor hypofunction in schizophrenia

Publication date: Available online 16 October 2019Source: Pharmacology &TherapeuticsAuthor(s): Kazu Nakazawa, Kiran SapkotaAbstractN-methyl-D-aspartate (NMDA) receptor (NMDAR) hypofunction plays a key role in pathophysiology of schizophrenia. Since NMDAR hypofunction has also been reported in autism, Alzheimer’s disease and cognitive dementia, it is crucial to identify the location, timing, and mechanism of NMDAR hypofunction for schizophrenia for better understanding of disease etiology and for novel therapeutic intervention. In this review, we first discuss the shared underlying mechanisms of NMDAR hypofunction in NMDAR antagonist models and the anti-NMDAR autoantibody model of schizophrenia and suggest that NMDAR hypofunction could occur in GABAergic neurons in both models. Preclinical models using transgenic mice have shown that NMDAR hypofunction in cortical GABAergic neurons, in particular parvalbumin-positive fast-spiking interneurons, in the early postnatal period confers schizophrenia-related phenotypes. Recent studies suggest that NMDAR hypofunction can also occur in PV-positive GABAergic neurons with alterations of NMDAR–associated proteins, such as neuregulin/ErbB4, α7nAChR, and serine racemase. Furthermore, several environmental factors, such as oxidative stress, kynurenic acid and hypoxia, may also potentially elicit NMDAR hypofunction in GABAergic neurons in early postnatal period. Altogether, the studies discussed here support a central r...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research

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Last year, Molecular Brain became the first BMC journal to introduce Micro Reports, an innovative way to quickly share research which would otherwise go unpublished as a full research paper. Micro Reports are short research summaries of up to 1200 words, ideal for publishing negative results, reproduced studies, smaller data sets which are still important but would not warrant a full research article, and brand new findings which should enter the public domain as soon as possible. Since the launch of this new article type, the journal has received 58 Micro Report submissions, with 24 publications to date. We’ve highl...
Source: BioMed Central Blog - Category: General Medicine Authors: Tags: Biology Open Access Publishing Molecular Brain neuroscience SfN19 Source Type: blogs
__________ Industry review boards are needed to protect VR user privacy (World Economic Forum blog): “It seemed like a game when Riley first started the virtual reality (VR) maze … A month after playing the game, Riley was turned down for a new life-insurance policy. Given his excellent health, he couldn’t understand why. Several appeals later, the insurance company disclosed that Riley’s tracking data from the VR maze game revealed behavioral movement patterns often seen among people in the very early stages of dementia … This is a hypothetical situation, but the science of using movements ...
Source: SharpBrains - Category: Neuroscience Authors: Tags: Cognitive Neuroscience Health & Wellness Technology AR biometric Cognitive-tests dementia FDA institutional review boards insurance IRB movement patterns neurorehabilitation neurotechnologies Neurotechnology privacy virtual Source Type: blogs
AbstractNeurodegenerative disorders and ischemic conditions leading to the development of Alzheimer ’s and Parkinson’s diseases, vascular dementia, etc. have attracted attention of many researchers studying the mechanisms of abnormalities in the central nervous system (CNS). The genetic predisposition for these diseases has been reported in the studies of the last few decades. Current achievem ents in biochemistry and molecular biology have revealed the relationships between risk factors contributing to the development of these pathologies and target proteins controlled by the genome. It has been demonstrated t...
Source: Biochemistry (Moscow) - Category: Biochemistry Source Type: research
In this paper, we conduct a literature survey about various virtual reality (VR) treatments in psychiatry. We collect 36 studies that made use of VR to provide clinical trials or therapies for patients with psychiatric disorders. In order to gain a better understanding of the management of pain and stress, we first investigate VR applications for patients to alleviate pain and stress during immersive activities in a virtual environment. Particularly for anxiety, VR exposure therapies are effective in provoking realistic reactions to feared stimuli. On top of that, the exposure therapies with simulated images are beneficial...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
AbstractFrontotemporal dementia (FTD) is a highly heritable group of neurodegenerative disorders, with around 30% of patients having a strong family history. The majority of that heritability is accounted for by autosomal dominant mutations in the chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), and microtubule-associated protein tau (MAPT) genes, with mutations more rarely seen in a number of other genes. This review will discuss the recent updates in the field of genetic FTD. Age at symptom onset in genetic FTD is variable with recently identified genetic modifiers includingTMEM106B (inGRN carriers partic...
Source: Journal of Neurology - Category: Neurology Source Type: research
Conclusion: There may be an association between schizophrenia and HNPP. In observational studies, the deletion of interest (chromosome 17p12) was nearly 10 times more common in schizophreniform patients than in controls. This potential association could be pathophysiologically explained by the role of PMP22, which is mainly expressed in the peripheral nervous system. However, PMP22 mRNA and protein can also be found in the brain. PMP22 seems to play an important role in regulating cell growth and myelination, functions that are disturbed in schizophrenia. Such a connection obviously cannot be clarified on the basis of one ...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Novel Contribution of Secreted Amyloid-β Precursor Protein to White Matter Brain Enlargement in Autism Spectrum Disorder Deborah K. Sokol1, Bryan Maloney2, Cara J. Westmark3 and Debomoy K. Lahiri2,4* 1Pediatrics Section, Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, United States2Indiana Alzheimers Disease Center, Department of Psychiatry, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, United States3Department of Neurology, University of Wisconsin, Madison, WI, United States4Department of Medical and Molecular Genetics, Indiana Un...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: Available online 18 February 2019Source: NeuroscienceAuthor(s): Katherine Najera, B. Matthew Fagan, Peter M. ThompsonAbstractSynaptosomal Associated Protein-25 kilodaltons (SNAP-25) is an integral member of the SNARE complex. This complex is essential for calcium-triggered synaptic vesicular fusion and release of neurotransmitters into the synaptic cleft. In addition to neurotransmission, SNAP-25 is associated with insulin release, the regulation of intracellular calcium, and neuroplasticity. Because of SNAP-25's varied and crucial biological roles, the consequences of changes in this protein can be seen ...
Source: Neuroscience - Category: Neuroscience Source Type: research
AbstractWith continuing cooperation from 18 domestic and international brain banks over the last 36  years, we have analyzed the aluminum content of the temporal lobe neocortex of 511 high-quality human female brain samples from 16 diverse neurological and neurodegenerative disorders, including 2 groups of age-matched controls. Temporal lobes (Brodmann areas A20–A22) were selected for analysis because of their availability and their central role in massive information-processing operations including efferent-signal integration, cognition, and memory formation. We used the analytical technique of (i) Zeeman-type ...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
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