Astrocytes in the brain form an intimately associated network with neurons. They respond to neuronal activity and synaptically released glutamate by raising intracellular calcium concentration ([Ca2+]i), which could represent the start of back-signalling to neurons. Here we show that coactivation of the AMPA/kainate and metabotropic glutamate receptors (mGluRs) on astrocytes stimulates these cells to release glutamate through a Ca2+-dependent process mediated by prostaglandins. Pharmacological inhibition of prostaglandin synthesis prevents glutamate release, whereas application of prostaglandins (in particular PGE2) mimics and occludes the releasing action of GluR agonists. PGE2 promotes Ca2+-dependent glutamate release from cultured astrocytes and also from acute brain slices under conditions that suppress neuronal exocytotic release. When applied to the CA1 hippocampal region, PGE2 induces increases in [Ca2+]i both in astrocytes and in neurons. The [Ca2+]i increase in neurons is mediated by glutamate released from astrocytes, because it is abolished by GluR antagonists. Our results reveal a new pathway of regulated transmitter release from astrocytes and outline the existence of an integrated glutamatergic cross-talk between neurons and astrocytes in situ that may play critical roles in synaptic plasticity and in neurotoxicity.
"However, subsequent studies in situ rather indicated that the gap junctional communication between astrocytic and neuronal networks occurs at the early stages of neural development and lessens with the progression of differentiation (Alvarez-Maubecin et al., 2000; Bittman et al., 2002). It was therefore proposed that astrocytic Ca 2+ waves can affect the calcium concentration of the neighboring neurons by Ca 2+ -dependent release of various chemical transmitters , which can activate neuronal ionotropic and metabotropic receptors (Bezzi et al., 1998, 2001, 2004; Henneberger et al., 2010; Jourdain et al., 2007; Lalo et al., 2014; Mothet et al., 2005; Panatier et al., 2006; Parpura et al., 1994; Pascual et al., 2005; Santello et al., 2011; Slezak et al., 2012). Because a single astrocyte can contact thousands of synapses and hundreds of dendrites (Bushong et al., 2002; Halassa et al., 2007), one may hypothesize that the astrocytic networks can activate multiple neurons via the discharge of chemical transmitters. "
"Since Benveniste demonstrated that ischemic injury evoked release of glutamic acid (Glu) and aspartic acid (Asp) from the rat hippocampus (Benveniste et al., 1984), the changes of amino acids during cerebral ischemia–reperfusion have been of much research interests. Asp and Glu are released excessively from neurons and astrocytes after ischemic injury (Benveniste et al., 1984; Bezzi et al., 1998; Drejer et al., 1985; Katchman and Hershkowitz, 1993), which might contribute to the progressive neural injury. Glycine (Gly), Taurine (Tau) and g-aminobutyric acid (GABA) are inhibitory amino acids (IAA), which can inhibit the excess-activity of nerve cell caused by excitatory amino acids (EAA) (Shah et al., 2002). "
"In addition to NOX, the cyclooxygenase-2 (COX-2) enzymes have been found to upregulate ROS levels via the production of prostaglandins (specifically, F 2 and H) . In an in vitro model of rat cortex, it has been shown that the prostaglandins stimulate astrocytes to produce proinflammatory cytokines, which initiated neuronal death . COX-2 is also responsible for a number of inflammatory responses in tissues involving neutrophils of the immune system . "
[Show abstract][Hide abstract] ABSTRACT: An insult to the brain (such as the first seizure) causes excitotoxicity, neuroinflammation, and production of reactive oxygen/nitrogen species (ROS/RNS). ROS and RNS produced during status epilepticus (SE) overwhelm the mitochondrial natural antioxidant defense mechanism. This leads to mitochondrial dysfunction and damage to the mitochondrial DNA. This in turn affects synthesis of various enzyme complexes that are involved in electron transport chain. Resultant effects that occur during epileptogenesis include lipid peroxidation, reactive gliosis, hippocampal neurodegeneration, reorganization of neural networks, and hypersynchronicity. These factors predispose the brain to spontaneous recurrent seizures (SRS), which ultimately establish into temporal lobe epilepsy (TLE). This review discusses some of these issues. Though antiepileptic drugs (AEDs) are beneficial to control/suppress seizures, their long term usage has been shown to increase ROS/RNS in animal models and human patients. In established TLE, ROS/RNS are shown to be harmful as they can increase the susceptibility to SRS. Further, in this paper, we review briefly the data from animal models and human TLE patients on the adverse effects of antiepileptic medications and the plausible ameliorating effects of antioxidants as an adjunct therapy.
BioMed Research International 01/2015; 2015:745613. DOI:10.1155/2015/745613 · 2.71 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.