38 results match your criteria: "Institute of the Royal Academy of Arts and Sciences[Affiliation]"

Characterization of an immune-evading doxycycline-inducible lentiviral vector for gene therapy in the spinal cord.

Exp Neurol

September 2022

Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, An Institute of the Royal Academy of Arts and Sciences, Amsterdam, the Netherlands; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognition Research, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Article Synopsis
  • Gene therapy shows promise for spinal cord regeneration, but controlling gene expression timing is crucial to avoid side effects.
  • The doxycycline-inducible system used for gene expression faces challenges due to its reliance on a bacterial transactivator that can provoke immune responses, limiting its clinical use.
  • A new chimeric transactivator, GARrtTA, demonstrates improved immune evasion and lasts longer in spinal cord applications than the standard rtTA system, leading to healthier cells and reduced cytotoxic T-cell recruitment.
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A human neuroma-in continuity (NIC), formed following a peripheral nerve lesion, impedes functional recovery. The molecular mechanisms that underlie the formation of a NIC are poorly understood. Here we show that the expression of multiple genes of the Wnt family, including Wnt5a, is changed in NIC tissue from patients that underwent reconstructive surgery.

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A loss of mature microglial markers without immune activation in schizophrenia.

Glia

May 2021

Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University (BCRM-UMCU-UU), Utrecht, The Netherlands.

Microglia, the immune cells of the brain, are important for neurodevelopment and have been hypothesized to play a role in the pathogenesis of schizophrenia (SCZ). Although previous postmortem studies pointed toward presence of microglial activation, this view has been challenged by more recent hypothesis-driven and hypothesis-free analyses. The aim of the present study is to further understand the observed microglial changes in SCZ.

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GDNF Gene Therapy to Repair the Injured Peripheral Nerve.

Front Bioeng Biotechnol

October 2020

Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Institute of the Royal Academy of Arts and Sciences, Amsterdam, Netherlands.

A spinal root avulsion is the most severe proximal peripheral nerve lesion possible. Avulsion of ventral root filaments disconnects spinal motoneurons from their target muscles, resulting in complete paralysis. In patients that undergo brachial plexus nerve repair, axonal regeneration is a slow process.

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Findings from epidemiological studies, biomarker measurements and animal experiments suggest a role for aberrant immune processes in the pathogenesis of major depressive disorder (MDD). Microglia, the resident immune cells of the brain, are likely to play a key role in these processes. Previous post-mortem studies reported conflicting findings regarding microglial activation and an in-depth profiling of those cells in MDD is lacking.

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Contrast-Dependence of Temporal Frequency Tuning in Mouse V1.

Front Neurosci

August 2020

Cortical Structure and Function Group, Netherlands Institute for Neuroscience, Institute of the Royal Academy of Arts and Sciences, Amsterdam, Netherlands.

The perception of speed is influenced by visual contrast. In primary visual cortex (V1), an early stage in the visual perception pathway, the neural tuning to speed is directly related to the neural tuning to temporal frequency of stimulus changes. The influence of contrast on speed perception can be caused by the joint dependency of neural responses in V1 on temporal frequency and contrast.

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Ventral root avulsion leads to severe motoneuron degeneration and prolonged distal nerve denervation. After a critical period, a state of chronic denervation develops as repair Schwann cells lose their pro-regenerative properties and inhibitory factors such as CSPGs accumulate in the denervated nerve. In rats with ventral root avulsion injuries, we combined timed GDNF gene therapy delivered to the proximal nerve roots with the digestion of inhibitory CSPGs in the distal denervated nerve using sustained lentiviral-mediated chondroitinase ABC (ChABC) enzyme expression.

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Activity in Lateral Visual Areas Contributes to Surround Suppression in Awake Mouse V1.

Curr Biol

December 2019

Netherlands Institute for Neuroscience, an institute of the Royal Academy of Arts and Sciences, Amsterdam, Meibergdreef 47, 1105 BA Amsterdam, the Netherlands. Electronic address:

Neuronal response to sensory stimuli depends on the context. The response in primary visual cortex (V1), for instance, is reduced when a stimulus is surrounded by a similar stimulus [1-3]. The source of this surround suppression is partially known.

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Microglial activation in schizophrenia: Is translocator 18 kDa protein (TSPO) the right marker?

Schizophr Res

January 2020

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University (BCRM-UMCU-UU), 3584, CG, Utrecht, the Netherlands; Department of Psychiatry, Icahn School of Medicine, New York, USA; Mental Illness Research, Education and Clinical Center (MIRECC), James J Peters VA Medical Center, Bronx, NY, USA. Electronic address:

Positron emission tomography (PET) with translocator 18 kDa protein (TSPO) radioligands has frequently been used to investigate microglial activation in schizophrenia in vivo. However, the specificity of this marker is increasingly debated. Here we show that TSPO expression is 1) not increased in postmortem brain tissue of schizophrenia patients; 2) not correlated with expression of microglial activation markers; 3) not restricted to microglia; and 4) not upregulated in ex vivo activated human primary microglia.

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Increased number of T-lymphocytes in post-mortem brain tissue of patients with schizophrenia.

Schizophr Res

February 2020

Department of Psychiatry, Icahn School of Medicine, New York, USA; Mental Illness Research, Education and Clinical Center (MIRECC), James J Peters VA Medical Center, Bronx, NY, USA. Electronic address:

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Enhanced regeneration and reinnervation following timed GDNF gene therapy in a cervical ventral root avulsion.

Exp Neurol

November 2019

Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, An institute of the Royal Academy of Arts and Sciences, Amsterdam, The Netherlands; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognition research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Avulsion of spinal nerve roots is a severe proximal peripheral nerve lesion. Despite neurosurgical repair, recovery of function in human patients is disappointing, because spinal motor neurons degenerate progressively, axons grow slowly and the distal Schwann cells which are instrumental to supporting axon extension lose their pro-regenerative properties. We have recently shown that timed GDNF gene therapy (dox-i-GDNF) in a lumbar plexus injury model promotes axon regeneration and improves electrophysiological recovery but fails to stimulate voluntary hind paw function.

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Microglia in post-mortem brain tissue of patients with bipolar disorder are not immune activated.

Transl Psychiatry

May 2019

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University (BCRM-UMCU-UU), 3584 CG, Utrecht, The Netherlands.

Genetic, epidemiological, and biomarker studies suggest that the immune system is involved in the pathogenesis of bipolar disorder (BD). It has therefore been hypothesized that immune activation of microglia, the resident immune cells of the brain, is associated with the disease. Only a few studies have addressed the involvement of microglia in BD so far and a more detailed immune profiling of microglial activation is lacking.

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DNA methylation changes related to nutritional deprivation: a genome-wide analysis of population and in vitro data.

Clin Epigenetics

May 2019

Brain Center University Medical Center Utrecht, Department of Psychiatry, Utrecht University, A01.468, PO Box 85500, 3508, GA, Utrecht, The Netherlands.

Background: DNA methylation has recently been identified as a mediator between in utero famine exposure and a range of metabolic and psychiatric traits. However, genome-wide analyses are scarce and cross-sectional analyses are hampered by many potential confounding factors. Moreover, causal relations are hard to identify due to the lack of controlled experimental designs.

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Liprin alfa 2 gene expression is increased by cannabis use and associated with neuropsychological function.

Eur Neuropsychopharmacol

May 2019

Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, The Netherlands. Electronic address:

The relation of heavy cannabis use with decreased neuropsychological function has frequently been described but the underlying biological mechanisms are still largely unknown. This study investigates the relation of cannabis use with genome wide gene expression and subsequently examines the relations with neuropsychological function. Genome-wide gene expression in whole blood was compared between heavy cannabis users (N = 90) and cannabis naïve participants (N = 100) that were matched for psychotic like experiences.

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Neurosurgical repair in patients with proximal nerve lesions results in unsatisfactory recovery of function. Gene therapy for neurotrophic factors is a powerful strategy to promote axon regeneration. Glial cell line-derived neurotrophic factor (GDNF) gene therapy promotes motor neuron survival and axon outgrowth; however, uncontrolled delivery of GDNF results in axon entrapment.

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Microglia, the specialized innate immune cells of the CNS, play crucial roles in neural development and function. Different phenotypes and functions have been ascribed to rodent microglia, but little is known about human microglia (huMG) heterogeneity. Difficulties in procuring huMG and their susceptibility to cryopreservation damage have limited large-scale studies.

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Article Synopsis
  • - Under normal conditions, nocturnal rodents primarily eat during the night, but diets high in fat and sugar may cause them to eat more during the day.
  • - A study focused on how a high-fat high-sugar diet affects clock-gene expression related to feeding behavior in rats, showing changes in certain brain areas linked to reward.
  • - The findings indicate that while this diet disrupts gene expression patterns in some brain regions, it does not change overall eating patterns throughout the day and night.
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"Eyes Open - Eyes Closed" EEG/fMRI data set including dedicated "Carbon Wire Loop" motion detection channels.

Data Brief

June 2016

Clinical Affective Neuroimaging Laboratory, Otto-von-Guericke University, Magdeburg, Germany; Department of Behavioral Neurology, Leibniz Institute for Neurobiology, Magdeburg, Germany; Department of Psychiatry, Otto-von-Guericke University, Magdeburg, Germany; Department of Psychiatry, University Tübingen, Tübingen, Germany.

This data set contains electroencephalography (EEG) data as well as simultaneous EEG with functional magnetic resonance imaging (EEG/fMRI) data. During EEG/fMRI, the EEG cap was outfitted with a hardware-based add-on consisting of carbon-wire loops (CWL). These yielded six extra׳CWL׳ signals related to Faraday induction of these loops in the main magnetic field " (Masterton et al.

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The biology of microglia has become subject to intense study, as they are widely recognized as crucial determinants of normal and pathologic brain functioning. While they are well studied in animal models, it is still strongly debated what specifies most accurately the phenotype and functioning of microglia in the human brain. In this study, we therefore isolated microglia from postmortem human brain tissue of corpus callosum (CC) and frontal cortex (CTX).

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The dorsal column lesion model of spinal cord injury targets sensory fibres which originate from the dorsal root ganglia and ascend in the dorsal funiculus. It has the advantages that fibres can be specifically traced from the sciatic nerve, verifiably complete lesions can be performed of the labelled fibres, and it can be used to study sprouting in the central nervous system from the conditioning lesion effect. However, functional deficits from this type of lesion are mild, making assessment of experimental treatment-induced functional recovery difficult.

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Resting-state fMRI studies have gained widespread use in exploratory studies of neuropsychiatric disorders. Graph metrics derived from whole brain functional connectivity studies have been used to reveal disease-related variations in many neuropsychiatric disorders including major depression (MDD). These techniques show promise in developing diagnostics for these often difficult to identify disorders.

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Carbon-wire loop based artifact correction outperforms post-processing EEG/fMRI corrections--A validation of a real-time simultaneous EEG/fMRI correction method.

Neuroimage

January 2016

Clinical Affective Neuroimaging Laboratory, Otto-von-Guericke University, Magdeburg, Germany; Department of Behavioral Neurology, Leibniz Institute for Neurobiology, Magdeburg, Germany; Department of Psychiatry, Otto-von-Guericke University, Magdeburg, Germany. Electronic address:

Simultaneous EEG-fMRI combines two powerful neuroimaging techniques, but the EEG signal suffers from severe artifacts in the MRI environment that are difficult to remove. These are the MR scanning artifact and the blood-pulsation artifact--strategies to remove them are a topic of ongoing research. Additionally large, unsystematic artifacts are produced across the full frequency spectrum by the magnet's helium pump (and ventilator) systems which are notoriously hard to remove.

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Peripheral nerve injury results in the activation of a number of transcription factors (TFs) in injured neurons, some of which may be key regulators of the regeneration-associated gene (RAG) programme. Among known RAG TFs, ATF3, Smad1, STAT3 and c-Jun have all been linked to successful axonal regeneration and have known functional and physical interactions. We hypothesised that TF expression would promote regeneration of the central axon branch of DRG neurons in the absence of a peripheral nerve lesion and that simultaneous overexpression of multiple RAG TFs would lead to greater effects than delivery of a single TF.

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Preference for concentric orientations in the mouse superior colliculus.

Nat Commun

April 2015

Netherlands Institute for Neuroscience, an institute of the Royal Academy of Arts and Sciences, Cortical Structure &Function group, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands.

The superior colliculus is a layered structure important for body- and gaze-orienting responses. Its superficial layer is, next to the lateral geniculate nucleus, the second major target of retinal ganglion axons and is retinotopically organized. Here we show that in the mouse there is also a precise organization of orientation preference.

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Microstimulation of area V4 has little effect on spatial attention and on perception of phosphenes evoked in area V1.

J Neurophysiol

February 2015

Department of Vision and Cognition, Netherlands Institute for Neuroscience (an institute of the Royal Academy of Arts and Sciences of the Netherlands), Amsterdam, The Netherlands; Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, The Netherlands; and Psychiatry Department, Academic Medical Center, Amsterdam, The Netherlands

Previous transcranial magnetic stimulation (TMS) studies suggested that feedback from higher to lower areas of the visual cortex is important for the access of visual information to awareness. However, the influence of cortico-cortical feedback on awareness and the nature of the feedback effects are not yet completely understood. In the present study, we used electrical microstimulation in the visual cortex of monkeys to test the hypothesis that cortico-cortical feedback plays a role in visual awareness.

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