scholarly journals Maintenance of Synaptic Stability Requires Calcium-Independent Phospholipase A2Activity

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Julie Allyson ◽  
Xiaoning Bi ◽  
Michel Baudry ◽  
Guy Massicotte
Keyword(s):  
Synaptic Plasticity ◽  
Glutamate Receptors ◽  
Tau Phosphorylation ◽  
Brain Disorders ◽  
Neuronal Function ◽  
Calcium Dependent ◽  
Calcium Requirement ◽  
Synaptic Operation ◽  
Phospholipases A ◽  
Made In

Phospholipases A2(PLA2s) represent one of the largest groups of lipid-modifying enzymes. Over the years, significant advances have been made in understanding their potential physiological and pathological functions. Depending on their calcium requirement for activation, PLA2s are classified into calcium dependent and independent. This paper mainly focuses on brain calcium-independent PLA2(iPLA2) and on the mechanisms by which they influence neuronal function and regulate synaptic plasticity. Particular attention will be given to the iPLA2γisoform and its role in the regulation of synaptic glutamate receptors. In particular, the paper discusses the possibility that brain iPLA2γdeficiencies could destabilise normal synaptic operation and might contribute to the aetiology of some brain disorders. In this line, the paper presents new data indicating that iPLA2γdeficiencies accentuate AMPA receptor destabilization and tau phosphorylation, which suggests that this iPLA2isoform should be considered as a potential target for the treatment of Tau-related disorders.

scholarly journals NMDA and AMPA Receptor Autoantibodies in Brain Disorders: From Molecular Mechanisms to Clinical Features

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 77
Author(s):  
Fabrizio Gardoni ◽  
Jennifer Stanic ◽  
Diego Scheggia ◽  
Alberto Benussi ◽  
Barbara Borroni ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
Ampa Receptor ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
In Vivo Studies ◽  
Ionotropic Glutamate Receptors ◽  
Brain Disorders ◽  
Functional Impairments ◽  
Different Types

The role of autoimmunity in central nervous system (CNS) disorders is rapidly expanding. In the last twenty years, different types of autoantibodies targeting subunits of ionotropic glutamate receptors have been found in a variety of patients affected by brain disorders. Several of these antibodies are directed against NMDA receptors (NMDAR), mostly in autoimmune encephalitis, whereas a growing field of research has identified antibodies against AMPA receptor (AMPAR) subunits in patients with different types of epilepsy or frontotemporal dementia. Several in vitro and in vivo studies performed in the last decade have dramatically improved our understanding of the molecular and functional effects induced by both NMDAR and AMPAR autoantibodies at the excitatory glutamatergic synapse and, consequently, their possible role in the onset of clinical symptoms. In particular, the method by which autoantibodies can modulate the localization at synapses of specific target subunits leading to functional impairments and behavioral alterations has been well addressed in animal studies. Overall, these preclinical studies have opened new avenues for the development of novel pharmacological treatments specifically targeting the synaptic activation of ionotropic glutamate receptors.

scholarly journals Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy

2022 ◽  
Vol 14 ◽  
Author(s):  
Shuang Chen ◽  
Da Xu ◽  
Liu Fan ◽  
Zhi Fang ◽  
Xiufeng Wang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Glutamate Receptors ◽  
Neurological Disorders ◽  
Nerve Conduction ◽  
Ionotropic Glutamate Receptors ◽  
Future Studies ◽  
Excitatory Neurotransmission ◽  
The Relationship ◽  
Neuron Injury

Epilepsy is one of the most common neurological disorders characterized by recurrent seizures. The mechanism of epilepsy remains unclear and previous studies suggest that N-methyl-D-aspartate receptors (NMDARs) play an important role in abnormal discharges, nerve conduction, neuron injury and inflammation, thereby they may participate in epileptogenesis. NMDARs belong to a family of ionotropic glutamate receptors that play essential roles in excitatory neurotransmission and synaptic plasticity in the mammalian CNS. Despite numerous studies focusing on the role of NMDAR in epilepsy, the relationship appeared to be elusive. In this article, we reviewed the regulation of NMDAR and possible mechanisms of NMDAR in epilepsy and in respect of onset, development, and treatment, trying to provide more evidence for future studies.

Diffusion, Buffering, and Binding

1998 ◽  
Author(s):  
Christof Koch
Keyword(s):  
Synaptic Plasticity ◽  
Intracellular Calcium ◽  
Temporal Dynamics ◽  
Critical Concentration ◽  
Two Photon Microscopy ◽  
Calcium Dependent ◽  
Calcium Sensors ◽  
Free Intracellular Calcium ◽  
Messenger Molecules ◽  
Spatio Temporal

In Chap. 9 we introduced calcium ions and alluded to their crucial role in regulating the day-to-day life of neurons. The dynamics of the free intracellular calcium is controlled by a number of physical and chemical processes, foremost among them diffusion and binding to a host of different proteins, which serve as calcium buffers and as calcium sensors or triggers. Whereas buffers simply bind Ca2+ above some critical concentration, releasing it back into the cytoplasm when [Ca2+]i has been reduced below this level, certain proteins— such as calmodulin—change their conformation when they bind with Ca2+ ions, thereby activating or modulating enzymes, ionic channels, or other proteins. The calcium concentration inside the cell not only determines the degree of activation of calcium-dependent potassium currents but—much more importantly—is relevant for determining the changes in structure expressed in synaptic plasticity. As discussed in Chap. 13, it is these changes that are thought to underlie learning. Given the relevance of second messenger molecules, such as Ca2+, IP3, cyclic AMP and others, for the processes underlying growth, sensory adaptation, and the establishment and maintenance of synaptic plasticity, it is crucial that we have some understanding of the role that diffusion and chemical kinetics play in governing the behavior of these substances. Today, we have unprecedented access to the spatio-temporal dynamics of intracellular calcium in individual neurons using fluorescent calcium dyes, such as fura-2 or fluo-3, in combination with confocal or two-photon microscopy in the visible or in the infrared spectrum (Tsien, 1988; Tank et al., 1988; Hernández-Cruz, Sala, and Adams, 1990; Ghosh and Greenberg, 1995).

An Overview of EEG and MEG

2017 ◽  
pp. 38-44
Author(s):  
Riitta Hari ◽  
Aina Puce
Keyword(s):  
Visual Inspection ◽  
Low Noise ◽  
Clinical Diagnostics ◽  
Brain Disorders ◽  
Clinical Environment ◽  
Single Trial ◽  
Eeg Activity ◽  
Technical Developments ◽  
Very High ◽  
Made In

This chapter discusses the rather different histories of MEG and EEG. EEG has been used as a tool of clinical diagnostics since the 1930s with visual inspection of spontaneous EEG activity in patients suffering from various brain disorders, particularly epilepsy. For MEG, the evolution of applications has been the opposite: the first recordings were made in research laboratories and the recordings started by averaging a very high number of single trials, and it took some time before low-noise MEG equipment became available to allow single-trial analyses. Only with recent technical developments, especially with the advent of whole scalp–covering devices, has MEG become increasingly popular in the clinical environment. We discuss the evolution of both techniques with respect to the measurement of brain rhythms and evoked and event-related responses.

Remodeling of astrocytes, a prerequisite for synapse turnover in the adult brain? Insights from the oxytocin system of the hypothalamus

2006 ◽  
Vol 290 (5) ◽  
pp. R1175-R1182 ◽  
Author(s):  
Dionysia T. Theodosis ◽  
Andrei Trailin ◽  
Dominique A. Poulain
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Neuronal Activity ◽  
Adult Brain ◽  
Synaptic Connectivity ◽  
Excitatory Synapses ◽  
Neuronal Function ◽  
Physiological Conditions ◽  
Baseline Levels ◽  
Activity Dependent

Neurons, including their synapses, are generally ensheathed by fine processes of astrocytes, but this glial coverage can be altered under different physiological conditions that modify neuronal activity. Changes in synaptic connectivity accompany astrocytic transformations so that an increased number of synapses are associated with reduced astrocytic coverage of postsynaptic elements, whereas synaptic numbers are reduced on reestablishment of glial coverage. A system that exemplifies activity-dependent structural synaptic plasticity in the adult brain is the hypothalamo-neurohypophysial system, and in particular, its oxytocin component. Under strong, prolonged activation (parturition, lactation, chronic dehydration), extensive portions of somatic and dendritic surfaces of magnocellular oxytocin neurons are freed of intervening astrocytic processes and become directly juxtaposed. Concurrently, they are contacted by an increased number of inhibitory and excitatory synapses. Once stimulation is over, astrocytic processes again cover oxytocinergic surfaces and synaptic numbers return to baseline levels. Such observations indicate that glial ensheathment of neurons is of consequence to neuronal function, not only directly, for example by modifying synaptic transmission, but indirectly as well, by preparing neuronal surfaces for synapse turnover.

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