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https://www.readbyqxmd.com/read/27493839/pathophysiological-function-of-adamts-enzymes-on-molecular-mechanism-of-alzheimer-s-disease
#1
REVIEW
Murat Serdar Gurses, Mustafa Numan Ural, Mehmet Akif Gulec, Omer Akyol, Sumeyya Akyol
The extracellular matrix (ECM) is an environment that has various enzymes attended in regeneration and restoration processes which is very important to sustain physiological and biological functions of central nervous system (CNS). One of the participating enzyme systems in ECM turnover is matrix metalloproteinases. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS) is a unique family of ECM proteases found in mammals. Components of this family may be distinguished from the ADAM (A Disintegrin and Metalloproteinase) family based on the multiple copies of thrombospondin 1-like repeats...
August 2016: Aging and Disease
https://www.readbyqxmd.com/read/27457813/functional-analysis-of-rare-variants-found-in-schizophrenia-implicates-a-critical-role-for-git1-pak3-signaling-in-neuroplasticity
#2
M J Kim, J Biag, D M Fass, M C Lewis, Q Zhang, M Fleishman, S P Gangwar, M Machius, M Fromer, S M Purcell, S A McCarroll, G Rudenko, R T Premont, E M Scolnick, S J Haggarty
Although the pathogenesis of schizophrenia (SCZ) is proposed to involve alterations of neural circuits via synaptic dysfunction, the underlying molecular mechanisms remain poorly understood. Recent exome sequencing studies of SCZ have uncovered numerous single-nucleotide variants (SNVs); however, the majority of these SNVs have unknown functional consequences, leaving their disease relevance uncertain. Filling this knowledge gap requires systematic application of quantitative and scalable assays to assess known and novel biological functions of genes...
July 26, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27126278/distinct-neuroplasticity-processes-are-induced-by-different-periods-of-acrobatic-exercise-training
#3
Samira Salame, Priscila C Garcia, Caroline C Real, Juliana Borborema, Sandra R Mota-Ortiz, Luiz R G Britto, Raquel S Pires
Short and long-term physical exercise induce physiological and structural changes in brain motor areas. The relationship between changes of structural and synaptic proteins in brain motor areas and acrobatic exercise is less understood. Our aim was to evaluate the expression of synapsin I (SYS), synaptophysin (SYP), microtubule-associated protein 2 (MAP2), neurofilament (NF), and a marker for recent neuronal activity (Egr-1) in the motor cortex, striatum and cerebellum of adult rats subjected to acrobatic exercise (AE, for 1-4 weeks)...
July 15, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27018876/large-scale-ion-current-based-proteomic-investigation-of-the-rat-striatal-proteome-in-a-model-of-short-and-long-term-cocaine-withdrawal
#4
Shichen Shen, Xiaosheng Jiang, Jun Li, Robert M Straubinger, Mauricio Suarez, Chengjian Tu, Xiaotao Duan, Alexis C Thompson, Jun Qu
Given the tremendous detriments of cocaine dependence, effective diagnosis and patient stratification are critical for successful intervention yet difficult to achieve due to the largely unknown molecular mechanisms involved. To obtain new insights into cocaine dependence and withdrawal, we employed a reproducible, reliable, and large-scale proteomics approach to investigate the striatal proteomes of rats (n = 40, 10 per group) subjected to chronic cocaine exposure, followed by either short- (WD1) or long- (WD22) term withdrawal...
May 6, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/26854727/the-selectivity-and-promiscuity-of-brain-neuroregenerative-inhibitors-between-rock1-and-rock2-isoforms-an-integration-of-sb-qssr-modelling-qm-mm-analysis-and-in-vitro-kinase-assay
#5
L Zhu, Y Yang, X Lu
The Rho-associated kinases (ROCKs) have long been recognized as an attractive therapeutic target for various neurological diseases; selective inhibition of ROCK1 and ROCK2 isoforms would result in distinct biological effects on neurogenesis, neuroplasticity and neuroregeneration after brain surgery and traumatic brain injury. However, the discovery and design of isoform-selective inhibitors remain a great challenge due to the high conservation and similarity between the kinase domains of ROCK1 and ROCK2. Here, a structure-based quantitative structure-selectivity relationship (SB-QSSR) approach was used to correlate experimentally measured selectivity with the difference in inhibitor binding to the two kinase isoforms...
2016: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/26829074/combining-dopaminergic-facilitation-with-robot-assisted-upper-limb-therapy-in-stroke-survivors-a-focused-review
#6
Duc A Tran, Marta Pajaro-Blazquez, Jean-Francois Daneault, Jaime G Gallegos, Jose Pons, Felipe Fregni, Paolo Bonato, Ross Zafonte
Despite aggressive conventional therapy, lasting hemiplegia persists in a large percentage of stroke survivors. The aim of this article is to critically review the rationale behind targeting multiple sites along the motor learning network by combining robotic therapy with pharmacotherapy and virtual reality-based reward learning to alleviate upper extremity impairment in stroke survivors. Methods for personalizing pharmacologic facilitation to each individual's unique biology are also reviewed. At the molecular level, treatment with levodopa was shown to induce long-term potentiation-like and practice-dependent plasticity...
June 2016: American Journal of Physical Medicine & Rehabilitation
https://www.readbyqxmd.com/read/26804233/dissecting-structure-activity-relationships-of-crebinostat-brain-penetrant-hdac-inhibitors-for-neuroepigenetic-regulation
#7
Balaram Ghosh, Wen-Ning Zhao, Surya A Reis, Debasis Patnaik, Daniel M Fass, Li-Huei Tsai, Ralph Mazitschek, Stephen J Haggarty
Targeting chromatin-mediated epigenetic regulation has emerged as a potential avenue for developing novel therapeutics for a wide range of central nervous system disorders, including cognitive disorders and depression. Histone deacetylase (HDAC) inhibitors have been pursued as cognitive enhancers that impact the regulation of gene expression and other mechanisms integral to neuroplasticity. Through systematic modification of the structure of crebinostat, a previously discovered cognitive enhancer that affects genes critical to memory and enhances synaptogenesis, combined with biochemical and neuronal cell-based screening, we identified a novel hydroxamate-based HDAC inhibitor, here named neurinostat, with increased potency compared to crebinostat in inducing neuronal histone acetylation...
February 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/26786312/connections-of-the-mouse-orbitofrontal-cortex-and-regulation-of-goal-directed-action-selection-by-brain-derived-neurotrophic-factor
#8
Kelsey S Zimmermann, John A Yamin, Donald G Rainnie, Kerry J Ressler, Shannon L Gourley
BACKGROUND: Distinguishing between actions that are more likely or less likely to be rewarded is a critical aspect of goal-directed decision making. However, neuroanatomic and molecular mechanisms are not fully understood. METHODS: We used anterograde tracing, viral-mediated gene silencing, functional disconnection strategies, pharmacologic rescue, and designer receptors exclusively activated by designer drugs (DREADDs) to determine the anatomic and functional connectivity between the orbitofrontal cortex (OFC) and the amygdala in mice...
November 18, 2015: Biological Psychiatry
https://www.readbyqxmd.com/read/26260430/neuroplasticity-and-mri-a-perfect-match
#9
Julie Hamaide, Geert De Groof, Annemie Van der Linden
Numerous studies have illustrated the benefits of physical workout and cognitive exercise on brain function and structure and, more importantly, on decelerating cognitive decline in old age and promoting functional rehabilitation following injury. Despite these behavioral observations, the exact mechanisms underlying these neuroplastic phenomena remain obscure. This gap illustrates the need for carefully designed in-depth studies using valid models and translational tools which allow to uncover the observed events up to the molecular level...
May 1, 2016: NeuroImage
https://www.readbyqxmd.com/read/26247220/nmda-receptor-antagonists-for-depression-critical-considerations
#10
REVIEW
Gianluca Serafini, Xenia Gonda, Zoltan Rihmer, Maurizio Pompili, Paolo Girardi, Henry A Nasrallah, Mario Amore
BACKGROUND: Research studies suggest that glutamate dysfunction, in particular N-methyl-D-aspartate receptors (NMDARs) abnormalities, may be involved in the pathophysiology of major neuropsychiatric conditions. Increased glutamatergic excitotoxic activity may be found in some brain circuits of patients with major depression. According to several published reports, NMDAR antagonists may exert antidepressant activity, but the molecular changes associated with abnormal glutamatergic neurotransmission remain unclear...
August 2015: Annals of Clinical Psychiatry: Official Journal of the American Academy of Clinical Psychiatrists
https://www.readbyqxmd.com/read/25886852/identifying-candidate-drivers-of-alcohol-dependence-induced-excessive-drinking-by-assembly-and-interrogation-of-brain-specific-regulatory-networks
#11
Vez Repunte-Canonigo, William Shin, Leandro F Vendruscolo, Celine Lefebvre, Lena van der Stap, Tomoya Kawamura, Joel E Schlosburg, Mariano Alvarez, George F Koob, Andrea Califano, Pietro Paolo Sanna
BACKGROUND: A systems biology approach based on the assembly and interrogation of gene regulatory networks, or interactomes, was used to study neuroadaptation processes associated with the transition to alcohol dependence at the molecular level. RESULTS: Using a rat model of dependent and non-dependent alcohol self-administration, we reverse engineered a global transcriptional regulatory network during protracted abstinence, a period when relapse rates are highest...
2015: Genome Biology
https://www.readbyqxmd.com/read/25810926/neuroplasticity-underlying-the-comorbidity-of-pain-and-depression
#12
REVIEW
Lisa Doan, Toby Manders, Jing Wang
Acute pain induces depressed mood, and chronic pain is known to cause depression. Depression, meanwhile, can also adversely affect pain behaviors ranging from symptomology to treatment response. Pain and depression independently induce long-term plasticity in the central nervous system (CNS). Comorbid conditions, however, have distinct patterns of neural activation. We performed a review of the changes in neural circuitry and molecular signaling pathways that may underlie this complex relationship between pain and depression...
2015: Neural Plasticity
https://www.readbyqxmd.com/read/25733313/characterization-of-bipolar-disorder-patient-specific-induced-pluripotent-stem-cells-from-a-family-reveals-neurodevelopmental-and-mrna-expression-abnormalities
#13
J M Madison, F Zhou, A Nigam, A Hussain, D D Barker, R Nehme, K van der Ven, J Hsu, P Wolf, M Fleishman, C O'Dushlaine, S Rose, K Chambert, F H Lau, T Ahfeldt, E H Rueckert, S D Sheridan, D M Fass, J Nemesh, T E Mullen, L Daheron, S McCarroll, P Sklar, R H Perlis, S J Haggarty
Bipolar disorder (BD) is a common neuropsychiatric disorder characterized by chronic recurrent episodes of depression and mania. Despite evidence for high heritability of BD, little is known about its underlying pathophysiology. To develop new tools for investigating the molecular and cellular basis of BD, we applied a family-based paradigm to derive and characterize a set of 12 induced pluripotent stem cell (iPSC) lines from a quartet consisting of two BD-affected brothers and their two unaffected parents...
June 2015: Molecular Psychiatry
https://www.readbyqxmd.com/read/25706226/top-down-control-of-serotonin-systems-by-the-prefrontal-cortex-a-path-toward-restored-socioemotional-function-in-depression
#14
REVIEW
Collin Challis, Olivier Berton
Social withdrawal, increased threat perception, and exaggerated reassurance seeking behaviors are prominent interpersonal symptoms in major depressive disorder (MDD). Altered serotonin (5-HT) systems and corticolimbic dysconnectivity have long been suspected to contribute to these symptomatic facets; however, the underlying circuits and intrinsic cellular mechanisms that control 5-HT output during socioemotional interactions remain poorly understood. We review literature that implicates a direct pathway between the ventromedial prefrontal cortex (vmPFC) and dorsal raphe nucleus (DRN) in the adaptive and pathological control of social approach-avoidance behaviors...
July 15, 2015: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/25564392/early-life-stress-and-psychiatric-disorders-epidemiology-neurobiology-and-innovative-pharmacological-targets
#15
REVIEW
A Ventriglio, A Gentile, R J Baldessarini, A Bellomo
The modern concept of stress is based on responses to events or factors ("stressors") experienced as aversive, threatening or excessive for maintaining physiological equilibrium of an organism. Prolonged exposure to stressors, particularly during early life, is strongly associated with later psychiatric disorders. Underlying mechanistic connections between stress responses and development of psychiatric illnesses remain uncertain and typically appear to be nonspecific. Relevant candidate mechanisms are likely to include the hypothalamic-pituitary-adrenal (HPA) axis, marked by sustained excessive release of cortisol from the adrenal cortex...
2015: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/25413326/dna-microarray-based-analysis-of-voluntary-resistance-wheel-running-reveals-novel-transcriptome-leading-robust-hippocampal-plasticity
#16
Min Chul Lee, Randeep Rakwal, Junko Shibato, Koshiro Inoue, Hyukki Chang, Hideaki Soya
In two separate experiments, voluntary resistance wheel running with 30% of body weight (RWR), rather than wheel running (WR), led to greater enhancements, including adult hippocampal neurogenesis and cognitive functions, in conjunction with hippocampal brain-derived neurotrophic factor (BDNF) signaling (Lee et al., J Appl Physiol, 2012; Neurosci Lett., 2013). Here we aimed to unravel novel molecular factors and gain insight into underlying molecular mechanisms for RWR-enhanced hippocampal functions; a high-throughput whole-genome DNA microarray approach was applied to rats performing voluntary running for 4 weeks...
November 1, 2014: Physiological Reports
https://www.readbyqxmd.com/read/25330739/src-kinase-as-a-mediator-of-convergent-molecular-abnormalities-leading-to-nmdar-hypoactivity-in-schizophrenia
#17
A Banerjee, H-Y Wang, K E Borgmann-Winter, M L MacDonald, H Kaprielian, A Stucky, J Kvasic, C Egbujo, R Ray, K Talbot, S E Hemby, S J Siegel, S E Arnold, P Sleiman, X Chang, H Hakonarson, R E Gur, C-G Hahn
Numerous investigations support decreased glutamatergic signaling as a pathogenic mechanism of schizophrenia, yet the molecular underpinnings for such dysregulation are largely unknown. In the post-mortem dorsolateral prefrontal cortex (DLPFC), we found striking decreases in tyrosine phosphorylation of N-methyl-D aspartate (NMDA) receptor subunit 2 (GluN2) that is critical for neuroplasticity. The decreased GluN2 activity in schizophrenia may not be because of downregulation of NMDA receptors as MK-801 binding and NMDA receptor complexes in postsynaptic density (PSD) were in fact increased in schizophrenia cases...
September 2015: Molecular Psychiatry
https://www.readbyqxmd.com/read/25231644/identifying-the-role-of-micrornas-in-spinal-cord-injury
#18
REVIEW
Jun Dong, Meng Lu, Xijing He, Junkui Xu, Jie Qin, Zhijian Cheng, Baobao Liang, Dong Wang, Haopeng Li
Spinal cord injury (SCI) is medically and socioeconomically debilitating, and effective treatments are lacking. The elucidation of the pathophysiological mechanisms underlying SCI is essential for developing effective treatments for SCI. MicroRNAs (miRNAs) are small non-coding RNA molecules (18-24 nucleotides long) that regulate gene expression by interacting with specific target sequences. Recent studies suggest that miRNAs can act as post-transcriptional regulators to inhibit mRNA translation. Bioinformatic analyses indicate that the altered expression of miRNAs has an effect on critical processes of SCI physiopathology, including astrogliosis, oxidative stress, inflammation, apoptosis, and neuroplasticity...
November 2014: Neurological Sciences
https://www.readbyqxmd.com/read/25123366/-neurobiology-of-schizophrenia-new-findings-from-the-structure-to-the-molecules
#19
REVIEW
A Schmitt, B Malchow, D Keeser, P Falkai, A Hasan
During recent years improved methods in neuroimaging, molecular biology and genetics contributed to new insights into the neurobiology of schizophrenia. This review summarizes and discusses current findings and their impact on the pathophysiology of the disease. New magnetic resonance imaging (MRI) based methods allow investigation of small subregions of the hippocampus and structural and functional connectivity analyses using multimodal imaging approaches. Volume deficits are correlated with MRI spectroscopy based data of the glutamatergic and GABAergic systems and confirm the glutamate hypothesis of schizophrenia...
March 2015: Der Nervenarzt
https://www.readbyqxmd.com/read/24723864/common-mechanisms-of-pain-and-depression-are-antidepressants-also-analgesics
#20
Tereza Nekovarova, Anna Yamamotova, Karel Vales, Ales Stuchlik, Jitka Fricova, Richard Rokyta
Neither pain, nor depression exist as independent phenomena per se, they are highly subjective inner states, formed by our brain and built on the bases of our experiences, cognition and emotions. Chronic pain is associated with changes in brain physiology and anatomy. It has been suggested that the neuronal activity underlying subjective perception of chronic pain may be divergent from the activity associated with acute pain. We will discuss the possible common pathophysiological mechanism of chronic pain and depression with respect to the default mode network of the brain, neuroplasticity and the effect of antidepressants on these two pathological conditions...
2014: Frontiers in Behavioral Neuroscience
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