Search results for "Excitotoxicity"
showing 10 items of 49 documents
Obesity as a Risk Factor for Alzheimer’s Disease: Implication of Leptin and Glutamate
2019
Obesity is known to induce leptin and insulin resistance. Leptin is a peptide hormone synthesized in adipose tissue that mainly regulates food intake. It has been shown that insulin stimulates the production of leptin when adipocytes are exposed to glucose to encourage satiety; while leptin, via a negative feedback, decreases the insulin release and enhances tissue sensitivity to it, leading to glucose uptake for energy utilization or storage. Therefore, resistance to insulin is closely related to leptin resistance. Obesity in middle age has also been related to Alzheimer’s disease (AD). In recent years, the relation between impaired leptin signaling pathway and the onset of AD has been stu…
Involvement of cyclin-dependent kinase-5 in the kainic acid-mediated degeneration of glutamatergic synapses in the rat hippocampus
2011
Increased levels of glutamate causing excitotoxic damage accompany neurological disorders such as ischemia/stroke, epilepsy and some neurodegenerative diseases. Cyclin-dependent kinase-5 (Cdk5) is important for synaptic plasticity and is deregulated in neurodegenerative diseases. However, the mechanisms by which kainic acid (KA)-induced excitotoxic damage involves Cdk5 in neuronal injury are not fully understood. In this work, we have thus studied involvement of Cdk5 in the KA-mediated degeneration of glutamatergic synapses in the rat hippocampus. KA induced degeneration of mossy fiber synapses and decreased glutamate receptor (GluR)6/7 and post-synaptic density protein 95 (PSD95) levels in…
Focal Cortical Lesions Induce Bidirectional Changes in the Excitability of Fast Spiking and Non Fast Spiking Cortical Interneurons
2014
A physiological brain function requires neuronal networks to operate within a well-defined range of activity. Indeed, alterations in neuronal excitability have been associated with several pathological conditions, ranging from epilepsy to neuropsychiatric disorders. Changes in inhibitory transmission are known to play a key role in the development of hyperexcitability. However it is largely unknown whether specific interneuronal subpopulations contribute differentially to such pathological condition. In the present study we investigated functional alterations of inhibitory interneurons embedded in a hyperexcitable cortical circuit at the border of chronically induced focal lesions in mouse …
TMIC-49. POTASSIUM CHANNEL KIR4.1 AND GLUTAMINE SYNTHETASE ARE DYSREGULATED IN GLIOMA
2017
The potassium channel KIR4.1 (KCNJ10) and the glutamate catalyzing enzyme glutamine synthetase (GS) are highly expressed in glial cells of the central nervous system. Both glial proteins play important roles in the maintenance of neuronal activity and neurotransmission. Dysfunction of both proteins can result in altered neuronal excitability and may lead to excitotoxicity. We analyzed 35 snap frozen tissue blocks (glioblastoma [GBM], n=22; low grade astrocytoma (LGA), n=8; oligodendroglioma (OG), n=3; oligoastrocytoma, n=2). All glioma samples had a matching tissue specimen from both the tumor core and the adjacent normal-appearing infiltration zone. Molecular subtyping (MGMT, IDH1/2, 1p/19…
Cannabinoid CB1 receptors regulate neuronal TNF-α effects in experimental autoimmune encephalomyelitis.
2011
Abstract Cannabinoid CB1 receptors (CB1Rs) regulate the neurodegenerative damage of experimental autoimmune encephalomyelitis (EAE) and of multiple sclerosis (MS). The mechanism by which CB1R stimulation exerts protective effects is still unclear. Here we show that pharmacological activation of CB1Rs dampens the tumor necrosis factor α (TNFα)-mediated potentiation of striatal spontaneous glutamate-mediated excitatory postsynaptic currents (EPSCs), which is believed to cogently contribute to the inflammation-induced neurodegenerative damage observed in EAE mice. Furthermore, mice lacking CB1Rs showed a more severe clinical course and, in parallel, exacerbated alterations of sEPSC duration af…
Possible Pathomechanisms Responsible for Injury to the Central Nervous System in the Settings of Chronic Cerebrospinal Venous Insufficiency
2012
The discovery of stenoses in the azygous and internal jugular veins, the so-called chronic cerebrospinal venous insufficiency that accompanies multiple sclerosis, has enabled the reinterpretation of knowledge about this neurologic dis- ease. Pathologic venous outflow from the central nervous system appears to lead to two main problems. Firstly, it disas- sembles the blood-brain barrier and may allow the penetration of nervous parenchyma by glutamate and leukocytes. Sec- ondly, it may result in significant hypoperfusion of the brain and spinal cord. These two overlapping pathologies are likely to trigger plaques through caspase-1-driven pyroptosis of oligodendrocytes and to evoke neurodegene…
Glutamate Excitotoxicity in the Cerebellum Mediated by IL-1β
2013
Multiple sclerosis (MS) is the prototypic inflammatory demyelinating disorder of the CNS. Symptoms of cerebellar dysfunction, such as tremors and ataxia, are relatively common in MS, but available treatment options are generally of limited value. Although many clinical manifestations of MS are
Pre- and postsynaptic type-1 cannabinoid receptors control the alterations of glutamate transmission in experimental autoimmune encephalomyelitis
2013
Type-1 cannabinoid receptors (CB1R) are important regulators of the neurodegenerative damage in multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE). In GABAergic striatal neurons, CB1R stimulation exerts protective effects by limiting inflammation-induced potentiation of glutamate-mediated spontaneous excitatory postsynaptic currents (sEPSCs). Here we show that CB1R located on GABAergic or on glutamatergic neurons are differentially involved in the pre- and postsynaptic alterations of sEPSCs caused by EAE in the striatum. After induction of EAE, mice selectively lacking CB1R on GABAergic neurons (GABA-CB1R-KO) showed exacerbated alterations of sEPSC duration in GA…
Fructose-1,6-Bisphosphate Protects Hippocampal Rat Slices from NMDA Excitotoxicity
2019
Effects of fructose 1,6-bisphosphate (F-1,6-P2) towards N-methyl-d-aspartate NMDA excitotoxicity were evaluated in rat organotypic hippocampal brain slice cultures (OHSC) challenged for 3 h with 30 &mu
Reduction in the Motoneuron Inhibitory/Excitatory Synaptic Ratio in an Early-Symptomatic Mouse Model of Amyotrophic Lateral Sclerosis
2010
Excitotoxicity is a widely studied mechanism underlying motoneuron degeneration in amyotrophic lateral sclerosis (ALS). Synaptic alterations that produce an imbalance in the ratio of inhibitory/excitatory synapses are expected to promote or protect against motoneuron excitotoxicity. In ALS patients, motoneurons suffer a reduction in their synaptic coverage, as in the transition from the presymptomatic (2-month-old) to early-symptomatic (3-month-old) stage of the hSOD1(G93A) mouse model of familial ALS. Net synapse loss resulted from inhibitory bouton loss and excitatory synapse gain. Furthermore, in 3-month-old transgenic mice, remaining inhibitory but not excitatory boutons attached to mot…