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Brain disorders

Song Cai, Chuwen Ling, Jun Lu, Songwei Duan, Yingzhao Wang, Huining Zhu, Ruibang Lin, Liang Chen, Xingchang Pan, Muyi Cai, Huaiyu Gu
A primary pathogeny of epilepsy is excessive activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs). To find potential molecules to inhibit AMPARs, high-throughput screening was performed in a library of tetrapeptides in silico. Computational results suggest that some tetrapeptides bind stably to the AMPAR. We aligned these sequences of tetrapeptide candidates with those from in vitro digestion of the trout skin protein. Among salmon-derived products, Glu-Gly-Ala-Arg (EGAR) showed a high biological affinity toward AMPAR when tested in silico...
October 25, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Rowshanak Hashemiyoon, Jens Kuhn, Veerle Visser-Vandewalle
Gilles de la Tourette syndrome is a complex, idiopathic neuropsychiatric disorder whose pathophysiological mechanisms have yet to be elucidated. It is phenotypically heterogeneous and manifests more often than not with both motor and behavioral impairment, although tics are its clinical hallmark. Tics themselves present with a complex profile as they characteristically wax and wane and are often preceded by premonitory somatosensory sensations to which it is said a tic is the response. Highly comorbid with obsessive-compulsive disorder and attention deficit-hyperactivity disorder, it is purported to be an epigenetic, neurodevelopmental spectrum disorder with a complex genetic profile...
October 25, 2016: Brain Topography
Sanghee Yun, Ryan P Reynolds, Irene Masiulis, Amelia J Eisch
People diagnosed with neuropsychiatric disorders such as depression, anxiety, addiction or schizophrenia often have dysregulated memory, mood, pattern separation and/or reward processing. These symptoms are indicative of a disrupted function of the dentate gyrus (DG) subregion of the brain, and they improve with treatment and remission. The dysfunction of the DG is accompanied by structural maladaptations, including dysregulation of adult-generated neurons. An increasing number of studies using modern inducible approaches to manipulate new neurons show that the behavioral symptoms in animal models of neuropsychiatric disorders can be produced or exacerbated by the inhibition of DG neurogenesis...
October 26, 2016: Nature Medicine
Oscar Marín
There is a growing understanding that pathological genetic variation and environmental insults during sensitive periods in brain development have long-term consequences on brain function, which range from learning disabilities to complex psychiatric disorders such as schizophrenia. Furthermore, recent experiments in animal models suggest that therapeutic interventions during sensitive periods, typically before the onset of clear neurological and behavioral symptoms, might prevent or ameliorate the development of specific pathologies...
October 26, 2016: Nature Medicine
Anissa Abi-Dargham, Guillermo Horga
The field of medicine is moving toward the use of biomarkers for the optimization of individualized care. This is a particular challenge for the field of psychiatry, in which diagnosis is based on a descriptive collection of behaviors without the availability of any objective test to stratify patients. Neuroimaging techniques such as molecular imaging with positron-emission tomography (PET) or structural and functional magnetic resonance imaging (MRI) provide an opportunity to bring psychiatry from an era of subjective descriptive classification into objective and tangible brain-based measures...
October 26, 2016: Nature Medicine
Giorgia Quadrato, Juliana Brown, Paola Arlotta
Neuropsychiatric disorders such as autism spectrum disorder (ASD), schizophrenia (SCZ) and bipolar disorder (BPD) are of great societal and medical importance, but the complexity of these diseases and the challenges of modeling the development and function of the human brain have made these disorders difficult to study experimentally. The recent development of 3D brain organoids derived from human pluripotent stem cells offers a promising approach for investigating the phenotypic underpinnings of these highly polygenic disorders and for understanding the contribution of individual risk variants and complex genetic background to human pathology...
October 26, 2016: Nature Medicine
Kenji Sanada, Iñaki Zorrilla, Yusuke Iwata, Cristina Bermúdez-Ampudia, Ariel Graff-Guerrero, Mónica Martínez-Cengotitabengoa, Ana González-Pinto
Several studies have investigated the relationship between non-pharmacological interventions (NPIs) and peripheral brain-derived neurotrophic factor (BDNF) in schizophrenia patients. We conducted a systematic review and meta-analysis to review the efficacy of NPIs on peripheral serum and plasma BDNF in subjects with schizophrenia (including schizoaffective disorder). Meta-analyses were conducted to examine the effects of NPIs on blood BDNF levels by using the standardized mean differences (SMDs) between the intervention groups and controls...
October 24, 2016: International Journal of Molecular Sciences
Mohammad A Kaisar, Ravi K Sajja, Shikha Prasad, Vinay V Abhyankar, Taylor Liles, Luca Cucullo
The blood-brain barrier (BBB) is a dynamic biological interface which actively controls the passage of substances between the blood and the central nervous system (CNS). From a biological and functional standpoint, the BBB plays a crucial role in maintaining brain homeostasis inasmuch that deterioration of BBB functions are prodromal to many CNS disorders. Conversely, the BBB hinders the delivery of drugs targeting the brain to treat a variety of neurological diseases. Area covered: This article reviews recent technological improvements and innovation in the field of BBB modeling including static and dynamic cell-based platforms, microfluidic systems and the use of stem cells and 3D printing technologies...
October 26, 2016: Expert Opinion on Drug Discovery
Michael A Lee, Naveed Bakh, Gili Bisker, Emery N Brown, Michael S Strano
Cortisol is an important glucocorticoid hormone whose biochemistry influences numerous physiological and pathological processes. Moreover, it is a biomarker of interest for a number of conditions, including posttraumatic stress disorder, Cushing's syndrome, Addison's disease, and others. An implantable biosensor capable of real time monitoring of cortisol concentrations in adipose tissue may revolutionize the diagnosis and treatment of these disorders, as well as provide an invaluable research tool. Toward this end, a mathematical model, informed by the physiological literature, is developed to predict dynamic cortisol concentrations in adipose, muscle, and brain tissues, where a significant number of important processes with cortisol occur...
October 26, 2016: Advanced Healthcare Materials
Beomsue Kim, Suihan Feng, Seong-Wook Yun, Cheryl Leong, Rudrakanta Satapathy, Si Yan Diana Wan, Young-Tae Chang
Selection of a specific neural stem/progenitor cells (NSPCs) has attracted broad attention in regenerative medicine for neurological disorders. Here, we report a fluorescent probe, CDg13, and its application for isolating strong neurogenic NSPCs. In comparison to the NSPCs isolated by other biomarkers, CDg13-stained NSPCs showed higher capability to differentiate into neurons. Target identification revealed that the fluorescence intensity of the probe within cells is inversely proportional to the expression levels of mouse and human Abcg2 transporters...
October 26, 2016: Chembiochem: a European Journal of Chemical Biology
Bharat Bhusan Subudhi, Pratap Kumar Sahu
Oxidative stress in brain underlies the major neurological disorders including Alzheimer's disease (AD) and Parkinson's disease (PD). Peripherally, Angiotensin-II is a major effector of inflammation. Identification of its capacity to access brain during hypertension, as well as location of central rennin angiotensin system have led to its recognition as the major effector of oxidative stress in brain. Clinical uses of antioxidants to antagonize this oxidative stress have mostly failed. In this scenario, AT1 blockers have been investigated to prevent neurodegeneration...
October 24, 2016: Mini Reviews in Medicinal Chemistry
Jasmina Bakic, Gilles Pourtois, Marieke Jepma, Romain Duprat, Rudi De Raedt, Chris Baeken
BACKGROUND: Major depressive disorder (MDD) creates debilitating effects on a wide range of cognitive functions, including reinforcement learning (RL). In this study, we sought to assess whether reward processing as such, or alternatively the complex interplay between motivation and reward might potentially account for the abnormal reward-based learning in MDD. METHODS: A total of 35 treatment resistant MDD patients and 44 age matched healthy controls (HCs) performed a standard probabilistic learning task...
October 26, 2016: Depression and Anxiety
Aggeliki Giannakopoulou, George A Lyras, Nikolaos Grigoriadis
Neurogenesis is a well-characterized phenomenon within the dentate gyrus (DG) of the adult hippocampus. Aging and chronic degenerative disorders have been shown to impair hippocampal neurogenesis, but the consequence of chronic inflammation remains controversial. In this study the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis was used to investigate the long-term effects of T cell-mediated central nervous system inflammation on hippocampal neurogenesis. 5-Bromodeoxyuridine (BrdU)-labeled subpopulations of hippocampal cells in EAE and control mice (coexpressing GFAP, doublecortin, NeuN, calretinin, and S100) were quantified at the recovery phase, 21 days after BrdU administration, to estimate alterations on the rate and differentiation pattern of the neurogenesis process...
October 26, 2016: Journal of Neuroscience Research
Qiang Li, Yong Xiao, Yinghui Li, Lei Li, Na Lu, Zhi Xu, Xiaodong Mou, Shenqin Mao, Wei Wang, Yonggui Yuan
INTRODUCTION: Somatic symptom disorder (SSD) is an illness that occurs over a long time and results in significant disruption in daily life. Clinically, SSD patients typically express complaints that involve a variety of organ systems. However, the neural mechanism of SSD remains poorly understood. METHODS: Using resting-state functional magnetic resonance imaging, we investigated the characteristics of the regional basal brain function during resting state in patients with SSD...
October 2016: Brain and Behavior
Vincent Strehlow, Marielle E M Swinkels, Rhys H Thomas, Nora Rapps, Steffen Syrbe, Thomas Dorn, Johannes R Lemke
Prompted by the observations of juvenile myoclonic epilepsy (JME) in 22q11.2 deletion syndrome (22q11DS) and recurrent copy number variants in genetic generalized epilepsy (GGE), we searched for further evidence supporting a possible correlation of 22q11DS with GGE and with myoclonic seizures. Through routine diagnostics, we identified 3 novel individuals with the seemingly uncommon combination of 22q11DS and JME. We subsequently screened the literature for reports focussing on the epilepsy phenotype in 22q11DS...
September 2016: Molecular Syndromology
Elena Parrini, Valerio Conti, William B Dobyns, Renzo Guerrini
Malformations of cortical development (MCD) represent a major cause of developmental disabilities, severe epilepsy, and reproductive disadvantage. Genes that have been associated to MCD are mainly involved in cell proliferation and specification, neuronal migration, and late cortical organization. Lissencephaly-pachygyria-severe band heterotopia are diffuse neuronal migration disorders causing severe global neurological impairment. Abnormalities of the LIS1, DCX, ARX, RELN, VLDLR, ACTB, ACTG1, TUBG1, KIF5C, KIF2A, and CDK5 genes have been associated with these malformations...
September 2016: Molecular Syndromology
Ingo Helbig, Abou Ahmad N Tayoun
Epileptic encephalopathies are severe often intractable seizure disorders where epileptiform abnormalities contribute to a progressive disturbance in brain function. Often, epileptic encephalopathies start in childhood and are accompanied by developmental delay and various neurological and non-neurological comorbidities. In recent years, this concept has become virtually synonymous with a group of severe childhood epilepsies including West syndrome, Lennox-Gastaut syndrome, Dravet syndrome, and several other severe childhood epilepsies for which genetic factors are increasingly recognized...
September 2016: Molecular Syndromology
Shahid Bashir, Woo-Kyoung Yoo
The field of neuromodulation encompasses a wide spectrum of interventional technologies that modify the pathological activity within the nervous system to achieve a therapeutic effect. Therapy, including transcranial direct current stimulation, has shown promising results across a range of neurological and neuropsychiatric disorders. This article reviews the state-of-the-art of neuromodulation for addiction and discusses the opportunities and challenges available for clinicians and researchers interested in advancing the neuromodulation therapy...
October 2016: Annals of Neurosciences
Salvatore Torrisi, Camilla L Nord, Nicholas L Balderston, Jonathan P Roiser, Christian Grillon, Monique Ernst
The habenula, a portion of the epithalamus, is implicated in the pathophysiology of depression, anxiety and addiction disorders. Its small size and connection to other small regions prevent standard human imaging from delineating its structure and connectivity with confidence. Resting state functional connectivity is an established method for mapping connections across the brain from a seed region of interest. The present study takes advantage of 7 T fMRI to map, for the first time, the habenula resting state network with very high spatial resolution in 32 healthy human participants...
October 22, 2016: NeuroImage
Ameneh Zare-Shahabadi, Akram Ataei, Nima Rezaei
Through selective activation/inhibition or dissection of neuronal circuits, optogenetic tools have raised hopes for a better understanding of neuropsychiatric mechanisms and therapeutic targets for various disorders. Although, overcoming serious limitations resultin from conventional neuronal circuit study, this method has its own imperfections, such as optogenetic modulation of neural activity, using an internal, animal-generated, light source. In this review, limitations of external light delivery systems and possible approaches for using internal light sources in laboratory animals and perhaps, human being, are being addressed...
October 22, 2016: Life Sciences
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