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molecular, bases, neuroplasticity

Elena D Osipova, Oxana V Semyachkina-Glushkovskaya, Andrey V Morgun, Natalia V Pisareva, Natalia A Malinovskaya, Elizaveta B Boitsova, Elena A Pozhilenkova, Olga A Belova, Vladimir V Salmin, Tatiana E Taranushenko, Mami Noda, Alla B Salmina
The contribution of astrocytes and microglia to the regulation of neuroplasticity or neurovascular unit (NVU) is based on the coordinated secretion of gliotransmitters and cytokines and the release and uptake of metabolites. Blood-brain barrier (BBB) integrity and angiogenesis are influenced by perivascular cells contacting with the abluminal side of brain microvessel endothelial cells (pericytes, astrocytes) or by immune cells existing (microglia) or invading the NVU (macrophages) under pathologic conditions...
January 8, 2018: Reviews in the Neurosciences
Jill Campbell Stewart, Steven C Cramer
BACKGROUND AND PURPOSE: In many neurologic diagnoses, significant interindividual variability exists in the outcomes of rehabilitation. One factor that may impact response to rehabilitation interventions is genetic variation. Genetic variation refers to the presence of differences in the DNA sequence among individuals in a population. Genetic polymorphisms are variations that occur relatively commonly and, while not disease-causing, can impact the function of biological systems. The purpose of this article is to describe genetic polymorphisms that may impact neuroplasticity, motor learning, and recovery after stroke...
July 2017: Journal of Neurologic Physical Therapy: JNPT
Eduard R Mingazov, Gulnara R Khakimova, Elena A Kozina, Alexei E Medvedev, Olga A Buneeva, Ara S Bazyan, Michael V Ugrumov
Parkinson's disease (PD) is characterized by the appearance of motor symptoms many years after the onset of neurodegeneration, which explains low efficiency of therapy. Therefore, one of the priorities in neurology is to develop an early diagnosis and preventive treatment of PD, based on knowledge of molecular mechanisms of neurodegeneration and neuroplasticity in the nigrostriatal system. However, due to inability to diagnose PD at preclinical stage, research and development must be performed in animal models by comparing the nigrostriatal system in the models of asymptomatic and early symptomatic stages of PD...
April 29, 2017: Molecular Neurobiology
N S Bondarenko, L K Dilmukhametova, A Yu Kurina, A R Murtazina, A Ya Sapronova, A P Sysoeva, M V Ugrumov
The morphogenesis of individual organs and the whole organism occurs under the control of intercellular chemical signals mainly during the perinatal period of ontogenesis in rodents. In this study, we tested our hypothesis that the biologically active concentration of noradrenaline (NA) in blood in perinatal ontogenesis of rats is maintained due to humoral interaction between its central and peripheral sources based on their plasticity. As one of the mechanisms of plasticity, we examined changes in the secretory activity (spontaneous and stimulated release of NA) of NA-producing organs under deficiency of its synthesis in the brain...
March 2017: Biochemistry. Biokhimii︠a︡
J E Beilharz, N O Kaakoush, J Maniam, M J Morris
The western diet is known to have detrimental effects on cognition and the gut microbiota, but few studies have investigated how these may be related. Here, we examined whether a probiotic could prevent diet-induced memory deficits. Rats were pre-exposed to vehicle, low or high doses of VSL#3 for 2 weeks before half were switched from chow to a cafeteria diet (Caf) for 25 days; VSL#3 treatment continued until death. High-dose VSL#3 prevented the diet-induced memory deficits on the hippocampal-dependent place task, but the probiotic caused deficits on the perirhinal-dependent object task, irrespective of diet or dose...
March 14, 2017: Molecular Psychiatry
Stephen D Skaper, Laura Facci, Morena Zusso, Pietro Giusti
Neuroplasticity is not only shaped by learning and memory but is also a mediator of responses to neuron attrition and injury (compensatory plasticity). As an ongoing process it reacts to neuronal cell activity and injury, death, and genesis, which encompasses the modulation of structural and functional processes of axons, dendrites, and synapses. The range of structural elements that comprise plasticity includes long-term potentiation (a cellular correlate of learning and memory), synaptic efficacy and remodelling, synaptogenesis, axonal sprouting and dendritic remodelling, and neurogenesis and recruitment...
2017: CNS & Neurological Disorders Drug Targets
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
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...
March 2017: Molecular Psychiatry
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
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
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
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
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
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...
February 15, 2017: Biological Psychiatry
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
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
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
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
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
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
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