Open AccessAstrocyte Networks and Epilepsy: When Stars Collide
Author(s) -
Wong Michael
Publication year - 2009
Publication title -
epilepsy currents
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.415
H-Index - 22
eISSN - 1535-7511
pISSN - 1535-7597
DOI - 10.1111/j.1535-7511.2009.01310.x
Subject(s) - neuroscience , epilepsy , gliosis , glial fibrillary acidic protein , astrocyte , neurotransmission , biology , medicine , microbiology and biotechnology , pathology , receptor , genetics , immunohistochemistry , central nervous system
Gliosis is a pathological hallmark of posttraumatic epileptic foci, but little is known about these reactive astrocytes beyond their high glial fibrillary acidic protein (GFAP) expression. Using diolistic labeling, we show that cortical astrocytes lost their nonoverlapping domain organization in three mouse models of epilepsy: posttraumatic injury, genetic susceptibility, and systemic kainate exposure. Neighboring astrocytes in epileptic mice showed a 10‐fold increase in overlap of processes. Concurrently, spine density was increased on dendrites of excitatory neurons. Suppression of seizures by the common antiepileptic, valproate, reduced the overlap of astrocytic processes. Astrocytic domain organization was also preserved in APP transgenic mice expressing a mutant variant of human amyloid precursor protein despite a marked upregulation of GFAP. Our data suggest that loss of astrocytic domains was not universally associated with gliosis, but restricted to seizure pathologies. Reorganization of astrocytes may, in concert with dendritic sprouting and new synapse formation, form the structural basis for recurrent excitation in the epileptic brain. Astrocytes provide metabolic substrates to neurons in an activity‐dependent manner. However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap‐junction subunit proteins connexin 43 and 30 allow intercellular trafficking of glucose and its metabolites through astroglial networks. This trafficking is regulated by glutamatergic synaptic activity mediated by AMPA receptors. In the absence of extracellular glucose, the delivery of glucose or lactate to astrocytes sustains glutamatergic synaptic transmission and epileptiform activity only when they are connected by gap junctions. These results indicate that astroglial gap junctions provide an activity‐dependent intercellular pathway for the delivery of energetic metabolites from blood vessels to distal neurons.