The purpose of this article is to study peculiarities of activation of the frontal cortex and neurometabolism of the brain in children with ADHD. Materials and Methods. The authors used an omega tester in order to study the activation levels of the brain systems. The energy state of the brain was studied by means of computer-hardware NEC Results The article presents a brief review of modern studies of the formation mechanisms of attention deficit disorder with hyperactivity. The main results of the research indicate the specific features of the activation and cerebral energy metabolism in children with ADHD.
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Children with cerebral dysfunction are characterized by increased level and asymmetrical activation of the frontal cortex, which may indicate underdevelopment of cortical-subcortical and limbic-reticular mechanisms of the brain. The aggregate indicators of the level of permanent potential of the brain in children with ADHD are significantly higher than those of children with normal development. The greatest increase in SCP was detected in the frontal part of the brain which causes the violation of the functional systems providing arbitrary regulation.
Children with ADHD demonstrated a marked violation of the principle of spherical distribution of energy consumption: There was a significant correlation between neurometabolism of the cerebral cortex and the activation level, due to the violation of the functional activity of nonspecific reticulo-limbic-cortical neural connections. The authors conclude that the state of the activating mechanisms and neurometabolic reactions are important factors affecting the formation mechanisms of ADHD.
Citations 0. References Dopamine receptor DRD4 gene and stressful life events in persistent attention deficit hyperactivity disorder. We subsequently investigated the interaction of stressful life events with these two DRD4 polymorphisms, and the impact of such events on the severity of ADHD symptomatology.
The gene-by-environment analysis revealed an independent effect of stressful experiences on the severity of persistent ADHD, and a gene-by-environment interaction on the inattentive dimension of the disorder, where non carriers of the Dup bp L - VNTR 48bp 7R haplotype were more sensitive to environmental adversity than carriers. These results are in agreement with previous works reporting a relationship between DRD4 and the effect of adverse experiences, which may explain the discordant findings in previous genetic studies and strengthen the importance of gene-by-environment interactions on the severity of ADHD.
Modeling ADHD: A review of ADHD theories through their predictions for decision-making and reinforcement learning. Ziegnler S. Психофизиология функциональных состояний и познавательной деятельности здорового и больного человека: Институт мозга человека РАН, В А Илюхина. Илюхина В. Нехорошкова А. Панков М. Jan А Н Подоплекин. Подоплекин А. Энергетическая физиология мозга: Фокин В. Антидор, Feasibility of a short-tern setting and plasticity effects.
Doren J. International Journal of Psychophysiology,vol. A Systematic Review and Metaregression Analysis. Polanczyk G. Psychiatry,vol. Brain imaging genetics in ADHD and beyond — Mapping pathways from gene to disorder at different levels of complexity. Full-text available. Beyond gene-finding, neurobiological parameters, such as brain structure, connectivity, and function, have been used to link genetic variation to ADHD symptomatology.
Fifty-one eligible research articles described studies of 13 ADHD candidate genes. Almost exclusively, single genetic variants were studied, mostly focussing on dopamine-related genes.
While promising results have been reported, imaging genetics studies are thus far hampered by methodological differences in study design and analysis methodology, as well as limited sample sizes. Beyond reviewing imaging genetics studies, we also discuss the need for complementary approaches at multiple levels of biological complexity and emphasize the importance of combining and integrating findings across levels for a better understanding of biological pathways from gene to disease.
These may include multi-modal imaging genetics studies, bioinformatic analyses, and functional analyses of cell and animal models. Natalie Colaneri. Background Recent studies report that a significant number of adolescents misuse and divert prescription stimulants.
As prescribers of these medications, physicians have a unique opportunity to help prevent the improper use and unlawful distribution of these medications. This study evaluates the extent to which physicians employ prevention practices with their adolescent patients with ADHD and their perceptions of the effectiveness of these practices.
Methods A questionnaire was developed and mailed to child and adolescent psychiatrists, child neurologists, and developmental-behavioral pediatricians in the US.
Conversely, Many responding physicians do not regularly implement practices that may prevent stimulant misuse, and the majority thinks most prevention practices are not very effective. Conclusion Physicians should assume greater responsibility in the prevention of stimulant misuse and diversion by implementing prevention practices more often with their adolescent patients with ADHD.
With respect to the generalizability of these findings, it must be noted that the sample was limited to pediatric subspecialists and may be influenced by selection bias and response bias. Biological molecules in clinical stroke trials.
Stroke remains a leading cause of disability and mortality all over the world despite the efforts made towards improving treatment. Most of the clinical studies have not shown signifi cant benefi cial effects in the evaluation of various molecules for their neuroprotection and neurorecovery promoting properties. The new concept of multimodal, pleiotropic drugs has opened new perspectives in this fi eld.
This review focuses on clinical stroke studies with biologically active molecules such as erythropoietin, granulocyte-colony stimulating factor and Cerebrolysin. The influence of neurotrophic factors treatment on stroke volume. Cerebrolysin is a multimodal drug, with pleiotropic neuroprotective effects that simultaneously promotes neuroprotection while retaining the ability to influence neuroplasticity.
Cerebrolysin is approved for the treatment of stroke, traumatic brain injury and cognitive dysfunction. A randomized, double-blind, placebo-controlled clinical trial was conducted in sixty patients with acute supratentorial ischemic stroke.
The treatment period was 10 days. Stroke volume was measured in the first 24 hours after stroke onset using diffusion-weighted images, and it was measured again at 30 days after stroke using fluidattenuated inversion recovery images.
We demonstrated a positive effect from Cerebrolysin treatment to reduce ischemic stroke volume. Neuroprotection is a modern therapeutic concept that has some useful outcomes discussed in the literature, including for traumatic brain injury TBI. Scope and study design: This was a retrospective case-control study that was approved by the bioethics commission of the Bagdasar-Arseni Teaching Emergency Hospital, Bucharest, Romania. Materials and methods: Nineteen cases treated with Cerebrolysin versus 28 who did not receive this drug were included in this study.
Epidemiological, clinical, paraclinical, and functional parameters were evaluated, using the: Patients in the Cerebrolysin group had, on average, higher although not statistically significant FIM evolution values The effect size assessed on the GOS was 2. Additionally, the mean FIM value at admission of the Cerebrolysin group Discussion and conclusion: Transthyretin provides trophic support via megalin by promoting neurite outgrowth and neuroprotection in cerebral ischemia.
Transthyretin TTR is a protein whose function has been associated to binding and distribution of thyroid hormones in the body and brain.
Genomic instability in the brain: Chromosomal mosaicism in schizophrenia
However, little is known regarding the downstream signaling pathways triggered by wild-type TTR in the CNS either in neuroprotection of cerebral ischemia or in physiological conditions. Recombinant TTR significantly boosted neurite outgrowth in mice hippocampal neurons, both in number and length, independently of its ligands. This TTR neuritogenic activity is mediated by the megalin receptor and is lost in megalin-deficient neurons.
Moreover, under excitotoxic conditions, TTR stimulation rescued cell death and neurite loss in TTR KO hippocampal neurons, which are more sensitive to excitotoxic degeneration than WT neurons, in a megalin-dependent manner.
Our results indicate that TTR might be regarded as a neurotrophic factor, because it stimulates neurite outgrowth under physiological conditions, and promotes neuroprotection in ischemic conditions. May Inflammation. Salidroside is being investigated for its therapeutic potential in stroke because it is neuroprotective over an extended therapeutic window of time. After 24 h, we found that salidroside increased the neuronal nuclear protein NeuN and reduced the marker of microglia and macrophages CD11b in the peri-infarct area of the brain.
At the same time, salidroside increased the ratio of phosphorylated protein kinase B p-Akt to total Akt. The phosphoinositide 3-kinase PI3K inhibitor LY prevented this increase in p-Akt and reversed the inhibitory effects of salidroside on CD11b and inflammatory mediators.
Jun BMRI. Cerebrolysin was reported to be effective in the neurological improvement of patients with acute ischemic stroke AIS in experimental models, while data from clinical trials were inconsistent. We performed a meta-analysis to explore the efficacy and safety of cerebrolysin for AIS.
We investigated the efficacy and safety outcomes, respectively. Risk ratios and mean differences were pooled with fixed-effects model or random-effects model. Seven studies were identified, involving patients with AIS.
The summary results failed to demonstrate significant superiority of cerebrolysin in the assessment of efficacy outcomes of mRS and BI. Similarly, administration of cerebrolysin had neutral effects on safety outcomes compared with placebo, including mortality and SAE. However, the number of included studies was small, especially in the analysis of efficacy outcomes, which might cause publication bias and inaccurate between-studies variance in the meta-analysis.
Conclusively, although it seemed to be safe, routine use of cerebrolysin to improve the long-term rehabilitation after stroke could not be supported by available evidence.
Neuroprotective effects of honokiol: Neuroprotective effects of honokiol. The incidence of neurological disorders is growing in developed countries together with increased lifespan. Nowadays, there are still no effective treatments for neurodegenerative pathologies, which make necessary to search for new therapeutic agents. Natural products, most of them used in traditional medicine, are considered promising alternatives for the treatment of neurodegenerative diseases.
Honokiol is a natural bioactive phenylpropanoid compound, belonging to the class of neolignan, found in notable amounts in the bark of Magnolia tree, and has been reported to exert diverse pharmacological properties including neuroprotective activities. Honokiol can permeate the blood brain barrier and the blood-cerebrospinal fluid to increase its bioavailability in neurological tissues. Diverse studies have provided evidence on the neuroprotective effect of honokiol in the central nervous system, due to its potent antioxidant activity, and amelioration of the excitotoxicity mainly related to the blockade of glutamate receptors and reduction in neuroinflammation.
The present work summarizes what is currently known concerning the neuroprotective effects of honokiol and its potential molecular mechanisms of action, which make it considered as a promising agent in the treatment and management of neurodegenerative diseases.
Photothrombotic Stroke as a Model of Ischemic Stroke. The search of effective anti-stroke neuroprotectors requires various stroke models adequate for different aspects of the ischemic processes. The photothrombotic stroke model is particularly suitable for the study of cellular and molecular mechanisms underlying neurodegeneration, neuroprotection, and neuroregeneration. It is a model of occlusion of small cerebral vessels, which provides detailed study of molecular mechanisms of ischemic cell death and useful for search of potential anti-stroke agents.
Its advantages include well-defined location and size of ischemic lesion that are determined by the aiming of the laser beam at the predetermined brain region; easy impact dosing by changing light intensity and duration; low invasiveness and minimal surgical intervention without craniotomy and mechanical manipulations with blood vessel, which carry the risk of brain trauma; low animal mortality and prolonged sensorimotor impairment that provide long-term study of stroke consequences including behavior impairment and recovery; independence on genetic variations of blood pressure and vascular architecture; and high reproducibility.
This review describes the current application of the photothrombotic stroke model for the study of cellular and molecular mechanisms of stroke development and ischemic penumbra formation, as well as for the search of anti-stroke drugs.
The Dynamics of Concussion: Despite increasing public awareness and a growing body of literature on the subject of concussion, or mild traumatic brain injury, an urgent need still exists for reliable diagnostic measures, clinical care guidelines, and effective treatments for the condition. Complexity and heterogeneity complicate research efforts and indicate the need for innovative approaches to synthesize current knowledge in order to improve clinical outcomes. Methods from the interdisciplinary field of systems science, including models of complex systems, have been increasingly applied to biomedical applications and show promise for generating insight for traumatic brain injury.
The current study uses causal-loop diagramming to visualize relationships between factors influencing the pathophysiology and recovery trajectories of concussive injury, including persistence of symptoms and deficits.
The primary output is a series of preliminary systems maps detailing feedback loops, intrinsic dynamics, exogenous drivers, and hubs across several scales, from micro-level cellular processes to social influences.
Key system features, such as the role of specific restorative feedback processes and cross-scale connections, are examined and discussed in the context of recovery trajectories. This systems approach integrates research findings across disciplines and allows components to be considered in relation to larger system influences, which enables the identification of research gaps, supports classification efforts, and provides a framework for interdisciplinary collaboration and communication—all strides that would benefit diagnosis, prognosis, and treatment in the clinic.
A S Petrukhin O. Мany aspects of сerebrolysin treatment in a wide range of nervous system disorders in children are described. High efficacy and well tolerated therapy are revealed. These findings expand the perspectives of using сerebrolysin in pediatric neurology.
Show more. Literature Review Apoptosis: A guide for the perplexed. Robert S. The roots of confusion are suggested to lie not in superficial disagreements about the morphology and biochemistry of cell death, but in the lamentable disconnection of modern science from its philosophical foundations i. Renewed awareness of these issues might be the key to understanding that apoptosis is a created concept, not a real entity, and that the use of terms that defy definition has become an obstacle to clear thinking about preventable cell death.
P Rothwell. Rothwell P. Elsevier Health Sciences; Neurotrophic Factors Bucuresti: Df Muresanu. Clinical trials - A practical approach. Inflammatory Mechanisms after Ischemia and Stroke. Inflammation has been implicated as a secondary injury mechanism following ischemia and stroke. A variety of experimental models, including thromboembolic stroke, focal and global ischemia, have been used to evaluate the importance of inflammation.
The vasculature endothelium promotes inflammation through the upregulation of adhesion molecules such as ICAM, E-selectin, and P-selectin that bind, to circulating leukocytes and facilitate their migration into the CNS. Once in the CNS, the production of cytotoxic molecules may facilitate cell death.
The macrophage and microglial response to injury may either be beneficial by scavenging necrotic debris or detrimental by facilitating cell death in neurons that would otherwise recover. While many studies have tested these hypotheses, the importance of inflammation in these models is inconclusive. This review summarizes data regarding the role of the vasculature, leukocytes, blood-brain barrier, macrophages, and microglia after experimental and clinical stroke.
Motor recovery after stroke. Feb Phys Med Rehabil Clin. Fundamentals of Clinical Trials. Lawrence M. This is the fourth edition of a very successful textbook on clinical trials methodology, written by three recognized experts who have long and extensive experience in all areas of clinical trials.
Most chapters have been revised considerably from the third edition. A chapter on ethics has been added and topics such as noninferiority and adaptive designs now receive considerable discussion. There is much new material on adverse events, adherence, data monitoring, and issues in analysis. This book is intended for the clinical researcher who is interested in designing a clinical trial and developing a protocol.
It is also of value to researchers and practitioners who must critically evaluate the literature of published clinical trials and assess the merits of each trial and the implications for the care and treatment of patients.
The authors use numerous examples of published clinical trials from a variety of medical disciplines to illustrate the fundamentals.
The text is organized sequentially from defining the question to trial closeout. One chapter is devoted to each of the critical areas to aid the clinical trial researcher.
These areas include pre-specifying the scientific questions to be tested and appropriate outcome measures, determining the organizational structure, estimating an adequate sample size, specifying the randomization procedure, implementing the intervention and visit schedules for participant evaluation, establishing an interim data and safety monitoring plan, detailing the final analysis plan, and reporting the trial results according to the pre-specified objectives.
Although a basic introductory statistics course is helpful in maximizing the benefit of this book, a researcher or practitioner with limited statistical background would still find most if not all the chapters understandable and helpful. While the technical material has been kept to a minimum, the statistician may still find the principles and fundamentals presented in this text useful. This book has been successfully used for teaching courses in clinical trial methodology.
Genomic instability in the brain: Chromosomal mosaicism in schizophrenia | Request PDF
All rights aeserved. Focal ischaemic injury in the brain is related to both the intensity and the duration of the decrement in cerebral blood flow.
The ischaemic penumbra, an area characterised by levels of blood flow slightly greater than the ischaemic core itself, is a zone exhibiting preserved or even accentuated metabolic rate, apparently driven by recurrent ischaemic depolarisations.
Excitatory amino acid neurotransmitter release and raised levels of oxygen radical activity occur within it. The penumbra represents that region of the focal ischaemic lesion which is potentially amenable to metabolic neuroprotection, and several classes of neuroprotective agents are currently under clinical evaluation for stroke.
As the untreated penumbra deteriorates over time, animal studies indicate that therapy should be administered within a therapeutic window of no more than 3—6 h from stroke onset if it is to be successful. Towards a dynamical network view of brain ischemia and reperfusion. Part I: Background and preliminaries. Donald J. The general failure of neuroprotectants in clinical trials of ischemic stroke points to the possibility of a fundamental blind spot in the current conception of ischemic brain injury, the "ischemic cascade".
This is the first in a series of four papers whose purpose is to work towards a revision of the concept of brain ischemia by applying network concepts to develop a bistable model of brain ischemia.
This first paper sets the stage for developing the bistable model of brain ischemia. Necessary background in network theory is introduced using examples from developmental biology which, perhaps surprisingly, can be adapted to brain ischemia with only minor modification. Then, to move towards a network model, we extract two core generalizations about brain ischemia from the mass of empirical data.
First, we conclude that all changes induced in the brain by ischemia can be classified as either damage mechanisms that contribute to cell death, or stress responses that contribute to cell survival.
Second, we move towards formalizing the idea of the "amount of ischemia", I, as a continuous, nonnegative, monotonically increasing quantity. These two generalizations are necessary precursors to reformulating brain ischemia as a bistable network.
Brain drains: new insights into brain clearance pathways from lymphatic biology | Request PDF
Clinical Trials in Traumatic Brain Injury: Past Experience and Current Developments. Jan Neurotherapeutics. In this article, we review past and current experience in clinical trials of traumatic brain injuries TBIswe discuss limitations and challenges, and we summarize current directions. The focus is on severe and moderate TBIs.
A systematic literature search of the years from to revealed 27 large phase III trials in TBI; we were aware of a further 6 unpublished trials. Analysis of these 33 trials yielded interesting observations: Expression of costimulatory molecules B CD80B CD86and interleukin 12 cytokine in multiple sclerosis lesions. Resting autoreactive T cells are present in the circulation of normal individuals without pathologic consequences.
In autoimmune animal models, stimulation of these self-reactive T cells in the presence of costimulatory molecules B results in T cell-mediated autoimmune disease, whereas B stimulation generates regulatory autoreactive T cells that abrogate disease severity. Thus, reactivation in the brain of myelin-autoreactive T cells by antigen with costimulatory molecules may be a critical event in the pathophysiology of multiple sclerosis MSa putative autoimmune disease of central nervous system CNS myelin.
We investigated the expression of cytokines and costimulatory molecules in a panel of 41 histologically characterized CNS specimens from 15 MS and 10 control cases using semiquantitative reverse transcriptase-polymerase chain reaction and immunocytochemistry.
In four cases, vascular CNS infarcts with inflammation were compared with MS plaques from the same brain. We observed increased expression of B and interleukin IL 12p40 in acute MS plaques, particularly from early disease cases but not in inflammatory infarcts. B staining was localized predominantly to the lymphocytes in perivenular inflammatory cuffs but not the parenchyma. In contrast, B was expressed predominantly on macrophages both in MS lesions of varied time duration and in inflammatory infarcts.
These findings indicate that an early event in the initiation of MS involves upregulation of B and IL, resulting in conditions that maximally stimulate T cell activation and induction of T helper 1-type immune responses. Comparison of phenotypic and functional properties of immediately ex vivo and cultured human adult microglia. Sep GLIA. Burkhard Becher Jack P.
Microglial cells are resident cells of the CNS and are implicated as regulators and effectors of immune responses which occur within this compartment.
The current study describes the phenotype and function of microglia immediately upon isolation from the non-inflamed adult human CNS and the phenotypic changes which occur in these cells when maintained in tissue culture.
CD14 becomes expressed at high levels on the cells, suggesting that CD14 can serve as an apparent marker of microglia activation which is not based on changes in morphology or APC capacity. The capacity to characterize phenotypic and functional properties of microglia before and after activation provides an opportunity to determine means to manipulate the immune regulatory and effector properties of this cell type.
Further evidence that Cerebrolysin R protects cortical neurons from neurodegeneration in vitro.The future of genetic codes and BRAIN codes
The effects of Cerebrolysin on isolated chicken cortical neurons in an iron induced oxidative stress model and in a combined iron-glutamate model have been examined. Cerebrolysin not only prevented iron induced neurodegeneration, demonstrating that ionic iron was responsible for the cell damage, moreover, it increased the neuronal viability up to tenfold with respect to the controls.
Under these conditions cerebrolysin again clearly counteracted the in vitro destructive effects of glutamate. Besides consequences on the viability and survival of neurons Cerebrolysin increased abundance of the microtubule-associated protein MAP2, which is known to play a an important role in maintaining normal neuronal function.
Glutamate-induced neuron death requires mitochondrial calcium uptake. We have investigated the role of mitochondrial calcium buffering in excitotoxic cell death. Glutamate acts at NMDA receptors in cultured rat forebrain neurons to increase the intracellular free calcium concentration.
Although concurrent inhibition of mitochondrial calcium uptake substantially enhanced this cytoplasmic calcium increase, it significantly reduced glutamate-stimulated neuronal cell death. Mitochondrial inhibition did not affect nitric oxide production or MAP kinase phosphorylation, which have been proposed to mediate excitotoxicity.
These results indicate that very high levels of cytoplasmic calcium are not necessarily toxic to forebrain neurons, and that potential-driven uptake of calcium into mitochondria is required to trigger NMDA-receptor-stimulated neuronal death.
We have documented changes in the oligodendrocyte population during demyelinating insult to the adult CNS. Feeding of cuprizone to adult mice led to apoptotic death of mature oligodendrocytes followed by profound demyelination of the corpus callosum.
A regenerative response was initiated even during active demyelination. Oligodendrocyte progenitors have begun to proliferate and then accumulate within the lesion. Many of these cells may have migrated from the sub-ventricular zone and fornix before their accumulation in the demyelinating corpus callosum.
The accumulation of differentiating oligodendrocyte progenitors was followed closely by the reappearance of mature oligodendrocytes and remyelination. These results suggest that the mature oligodendroglial population depleted by apoptosis is replaced by a newly formed oligodendroglial population derived from progenitors; these accumulate and seem to differentiate during remyelination.
A calcium microdomain near NMDA receptors: On switch for ERK-dependent synapse-to-nucleus communication. Interestingly, it has been reported that a QFISH protocol can be used for automated identification of gene amplifications . Full-text available. Feb Ivan Y Iourov Ilia V. Human Molecular Neurocytogenetics.
Sep Purpose of Review During the last decade, genomics has delivered basic insight into somatic genome variations contributing to human neuronal diversity in health and disease. Here, we review research on somatic chromosomal mosaicism and chromosome instability in the developing and adult normal and diseased human brain, representing the emerging field of molecular neurocytogenetics.
Recent Findings Chromosome instability and somatic chromosomal mosaicism were found to be involved in human brain development. Additionally, recent studies have highlighted the impact of neuronal aneuploidy and brain-specific chromosome instability on normal and pathological neurodevelopment and brain aging. Summary Neurocytogenomic variations are nowadays thought to play a critical role in human brain development and aging.
Chromosome instability is likely to be an element of pathogenetic cascades in a variety of brain diseases. Finally, human molecular neurocytogenetics may be recognized as an integral component of current biomedical science. Yuri B. Yurov Dec Ivan Y Iourov.
Mosaic Brain Aneuploidy in Mental Illnesses: Postzygotic chromosomal variation in neuronal cells is hypothesized to make a substantial contribution to the etiology and pathogenesis of neuropsychiatric disorders.
However, the role of somatic genome instability and mosaic genome variations in common mental illnesses is a matter of conjecture. Materials and methods: To estimate the pathogenic burden of somatic chromosomal mutations, we determined the frequency of mosaic aneuploidy in autopsy brain tissues of subjects with schizophrenia and other psychiatric disorders intellectual disability comorbid with autism spectrum disorders.
Reviewing these data and literature supports the hypothesis suggesting that an association of low-level mosaic aneuploidy with common and, probably, overlapping psychiatric disorders does exist. Accordingly, we propose a pathway for common neuropsychiatric disorders involving increased burden of rare de novo somatic chromosomal mutations manifesting as low-level mosaic aneuploidy mediating local and general brain dysfunction.
Show more. Technological Solutions in Human Interphase Cytogenetics. S G Vorsanova. Numerous interphase molecular cytogenetic approaches are useful for the analysis of chromosomes in normal and abnormal human cells. Interphase fluorescence in situ hybridization techniques offer unique possibilities to visualize individual chromosomes or chromosomal regions in single nondividing cells isolated from any given tissue. Despite technological difficulties encountered during studying human interphase chromosomes in health and disease, molecular cytogenetics or cytogenomics chromosomics does provide solutions for high-resolution single-cell analysis of genome organization, structure, and behavior at all stages of the cell cycle.
However, usually relatively little attention is paid to interphase molecular cytogenetics in current biomedical literature. Looking through the voluminous amount of original research papers and reviews dedicated to human interphase chromosomes, one can conclude that the technological aspects of studying human interphase chromosomes applied to basic and clinical research are rarely addressed. In an attempt to fill this gap, the present chapter provides a description of technological solutions in human interphase cytogenetics.
All rights are reserved. Assessment of copy number variations in the brain genome of schizophrenia patients. Jul Cytogenomic mutations and chromosomal abnormality are implicated in the neuropathology of several brain diseases.
In the present study, we analyzed gene dosage alterations in brain DNA of schizophrenia patients and compared those with the copy number variations CNVs identified in schizophrenia patients as well as with those in Asian lymphocyte DNA and attempted to obtain hints at the pathological contribution of cytogenomic instability to schizophrenia.
We found that the relative gene dosage of 85 regions significantly varied among a million of probe sites. The majority of these candidate CNVs exhibited high statistical probabilities but their signal differences in gene dosage were less than 1.
For test evaluation, we rather selected the 10 candidate CNV regions that exhibited higher aberration scores or larger global effects and were thus confirmable by PCR. Quantitative PCR verified the loss of gene dosage at two loci 1p These test loci, however, exhibited the same somatic CNV patterns in the other brain region. The present study lists the candidate regions potentially representing cytogenomic CNVs in the brain of schizophrenia patients, although the significant but modest alterations in their brain genome doses largely remain to be characterized further.