Search results for "OTR"
showing 10 items of 6791 documents
Effects of PSA Removal from NCAM on the Critical Period Plasticity Triggered by the Antidepressant Fluoxetine in the Visual Cortex.
2016
Neuronal plasticity peaks during critical periods of postnatal development and is reduced towards adulthood. Recent data suggests that windows of juvenile-like plasticity can be triggered in the adult brain by antidepressant drugs such as Fluoxetine. Although the exact mechanisms of how Fluoxetine promotes such plasticity remains unknown, several studies indicate that inhibitory circuits play an important role. The polysialylated form of the neural cell adhesion molecules (PSA-NCAM) has been suggested to mediate the effects of Fluoxetine and it is expressed in the adult brain by mature interneurons. Moreover, the enzymatic removal of PSA by neuroaminidase-N not only affects the structure of…
Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior
2020
Summary The nucleus accumbens (NAc) plays a key role in drug-related behavior and natural reward learning. Synaptic plasticity in dopamine D1 and D2 receptor medium spiny neurons (MSNs) of the NAc and the endogenous cannabinoid (eCB) system have been implicated in reward seeking. However, the precise molecular and physiological basis of reward-seeking behavior remains unknown. We found that the specific deletion of metabotropic glutamate receptor 5 (mGluR5) in D1-expressing MSNs (D1miRmGluR5 mice) abolishes eCB-mediated long-term depression (LTD) and prevents the expression of drug (cocaine and ethanol), natural reward (saccharin), and brain-stimulation-seeking behavior. In vivo enhancement…
Hippocampal hyperexcitability is modulated by microtubule-active agent: evidence from in vivo and in vitro epilepsy models in the rat
2016
The involvement of microtubule dynamics on bioelectric activity of neurons and neurotransmission represents a fascinating target of research in the context of neural excitability. It has been reported that alteration of microtubule cytoskeleton can lead to profound modifications of neural functioning, with a putative impact on hyperexcitability phenomena. Altogether, in the present study we pointed at exploring the outcomes of modulating the degree of microtubule polymerization in two electrophysiological epileptiform activity in the rat hippocampus. To this aim, we used in vivo Maximal Dentate Activation (MDA) and in vitro hippocampal epileptiform bursting activity (HEBA) paradigms to asse…
The Amino Acid Transporter JhI-21 Coevolves with Glutamate Receptors, Impacts NMJ Physiology, and Influences Locomotor Activity in Drosophila Larvae
2015
AbstractChanges in synaptic physiology underlie neuronal network plasticity and behavioral phenomena, which are adjusted during development. The Drosophila larval glutamatergic neuromuscular junction (NMJ) represents a powerful synaptic model to investigate factors impacting these processes. Amino acids such as glutamate have been shown to regulate Drosophila NMJ physiology by modulating the clustering of postsynaptic glutamate receptors and thereby regulating the strength of signal transmission from the motor neuron to the muscle cell. To identify amino acid transporters impacting glutmatergic signal transmission, we used Evolutionary Rate Covariation (ERC), a recently developed bioinforma…
Oxidative stress biomarkers in Fabry disease: is there a room for them?
2020
Abstract Background Fabry disease (FD) is an X-linked lysosomal storage disorder, caused by deficient activity of the alpha-galactosidase A enzyme leading to progressive and multisystemic accumulation of globotriaosylceramide. Recent data point toward oxidative stress signalling which could play an important role in both pathophysiology and disease progression. Methods We have examined oxidative stress biomarkers [Advanced Oxidation Protein Products (AOPP), Ferric Reducing Antioxidant Power (FRAP), thiolic groups] in blood samples from 60 patients and 77 healthy controls. Results AOPP levels were higher in patients than in controls (p < 0.00001) and patients presented decreased levels of…
TSH/IGF-1 Receptor Cross-Talk Rapidly Activates Extracellular Signal-Regulated Kinases in Multiple Cell Types
2017
We previously showed that thyrotropin (TSH)/insulinlike growth factor (IGF)-1 receptor cross-talk appears to be involved in Graves’ orbitopathy (GO) pathogenesis and upregulation of thyroid-specific genes in human thyrocytes. In orbital fibroblasts from GO patients, coadministration of TSH and IGF-1 induces synergistic increases in hyaluronan secretion. In human thyrocytes, TSH plus IGF-1 synergistically increased expression of the sodium-iodide symporter that appeared to involve ERK1/2 activation. However, the details of ERK1/2 activation were not known, nor was whether ERK1/2 was involved in this synergism in other cell types. Using primary cultures of GO fibroblasts (GOFs) and human thyr…
Alzheimer's disease: Only prevention makes sense
2018
Alzheimer's disease therapeutics is one of the most important endeavours in today's clinical investigation. Over more than 30 years of research, no disease-modifying treatment has been approved by either the FDA or the EMA to treat Alzheimer's disease. Recently, the evidence of pathological alterations in the brain tissue has been gathered showing that the signs of brain damage appear more than 20 years before the onset of Alzheimer's dementia. The major aim of this review is to underpin the idea that in Alzheimer's therapeutics, only prevention makes sense. It is difficult to visualise that would-be patients may be treated with endovenous administration of antibodies for several years to d…
Neurotrophic and neuroprotective effects of muscle contraction
2016
Background: Physical activity has been shown to be associated with reduced risk of coronary heart disease but the same effect seems to be produced in neurological diseases. Objective: In this review, we focused on the interplay between physical activity and some neurological conditions (Stroke, dementia, epilepsy, headache, Parkinson’ s disease, amyotrophic lateral sclerosis, multiple sclerosis, insomnia, depression and anxiety) with the aim of describing the potential role of physical activity in the prevention of such diseases and the physiological mechanisms involved in these processes. Results: Despite a growing body of evidence which reveals that physical activity is able to reduce the…
Neurotransmitters and Behavioral Alterations Induced by Nickel Exposure.
2020
Background:: Nickel ions (Ni2+) are a heavy metal with wide industrial uses. Environmental and occupational exposures to Ni are potential risk factors for brain dysfunction and behavioral and neurological symptoms in humans. Methods: We reviewed the current evidence about neurochemical and behavioral alterations associated with Ni exposure in laboratory animals and humans. Results: Ni2+ exposure can alter (both inhibition and stimulation) dopamine release and inhibit glutamate NMDA receptors. Few reports claim an effect of Ni2+ at the level of GBA and serotonin neurotransmission. At behavioral levels, exposure to Ni2+ in rodents alters motor activity, learning and memory as well as anxiety…
TSH/IGF-1 Receptor Cross Talk in Graves' Ophthalmopathy Pathogenesis.
2016
AbstractContext:The TSH receptor (TSHR) is considered the main target of stimulatory autoantibodies in the pathogenesis of Graves' ophthalmopathy (GO); however, it has been suggested that stimulatory IGF-1 receptor (IGF-1R) autoantibodies also play a role.Objective:We previously demonstrated that a monoclonal stimulatory TSHR antibody, M22, activates TSHR/IGF-1R cross talk in orbital fibroblasts/preadipocytes obtained from patients with GO (GO fibroblasts [GOFs]). We show that cross talk between TSHR and IGF-1R, not direct IGF-1R activation, is involved in the mediation of GO pathogenesis stimulated by Graves' autoantibodies.Design/Setting/Participants:Immunoglobulins were purified from the…