Glutamate transporters alterations in the reorganizing dentate gyrus are associated with progressive seizure activity in chronic epileptic rats.
The expression of glial and neuronal glutamate transporter proteins was investigated in the hippocampal region at different time points after electrically induced status epilepticus (SE) in the rat. This experimental rat model for mesial temporal lobe epilepsy is characterized by cell loss, gliosis, synaptic reorganization, and chronic seizures after a latent period. Despite extensive gliosis, immunocytochemistry revealed only an up-regulation of both glial transporters localized at the outer aspect of the inner molecular layer (iml) in chronic epileptic rats. The neuronal EAAC1 transporter was increased in many somata of individual CA1-3 neurons and granule cells that had survived after SE; this up-regulation was still present in the chronic epileptic phase. In contrast, a permanent decrease of EAAC1 immunoreactivity was observed in the iml of the dentate gyrus. This permanent decrease in EAAC1 expression, which was only observed in rats that experienced progressive spontaneous seizure activity, could lead to abnormal glutamate levels in the iml once new abnormal glutamatergic synaptic contacts are formed by means of sprouted mossy fibers. Considering the steady growth of reorganizing mossy fibers in the iml, the absence of a glutamate reuptake mechanism in this region could contribute to progression of spontaneous seizure activity, which occurs with a similar time course.
Gorter
Jan A
JA
Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 SM, Amsterdam, The Netherlands. gorter@science.uva.nl
Van Vliet
Erwin A
EA
Proper
Evelien A
EA
De Graan
Pierre N E
PN
Ghijsen
Wim E J M
WE
Lopes Da Silva
Fernando H
FH
Aronica
Eleonora
E
D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology; D004558:Electric Stimulation; D004827:Epilepsy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013226:Status Epilepticus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D027981:Symporters; D015854:Up-Regulation / Q000502:physiology
D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D018094:Receptors, Metabotropic Glutamate; C493398:Slc1a1 protein, rat; D027981:Symporters; C108822:metabotropic glutamate receptor 2; D018698:Glutamic Acid