Glutamate receptor 1-immunopositive neurons in the gliotic CA1 area of the mouse hippocampus after pilocarpine-induced status epilepticus.
Significant reduction in glutamate receptor 1 (GluR1)- and GluR2/3-immunopositive neurons was demonstrated in the hilus of the dentate gyrus in mice killed on days 1, 7 and 60 after pilocarpine-induced status epilepticus (PISE). In addition, GluR1 and GluR2/3 immunostaining in the strata oriens, radiatum and lacunosum moleculare of areas CA1-3 decreased drastically on days 7 and 60 after PISE. Neuronal loss observed in the above regions may account, at least in part, for a decrease in GluR immunoreactivity. By contrast, many GluR1-immunopositive neurons were observed in the gliotic area of CA1. Of these, about 42.8% were immunopositive for markers for hippocampal interneurons, namely calretinin (7.6%), calbindin (12.8%) and parvalbumin (22.4%). GluR1 or GluR2/3 and BrdU double-labelling showed that the GluR1- and GluR2/3-immunopositive neurons at 60 days after PISE were neurons that had survived rather than newly generated neurons. Furthermore, anterograde tracer and double-labelling studies performed on animals at 60 days after PISE indicated a projection from the hilus of the dentate gyrus to gliotic areas in both CA3 and CA1, where the projecting fibres apparently established connections with GluR1-immunopositive neurons. The projection to CA1 was unexpected. These novel findings suggest that the intrinsic hippocampal neuronal network is altered after PISE. We speculate that GluR1-immunopositive neurons in gliotic CA1 act as a bridge between dentate gyrus and subiculum contributing towards epileptogenesis.
Tang
Feng Ru
FR
Epilepsy Research Laboratory, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433. Feng_Ru_Tang@nni.com.sg
Chia
Shwn Chin
SC
Zhang
Si
S
Chen
Peng Min
PM
Gao
Hong
H
Liu
Chun Ping
CP
Khanna
Sanjay
S
Lee
Wei Ling
WL
D000818:Animals; D001522:Behavior, Animal; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D004569:Electroencephalography; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000473:pathology; D018721:Muscarinic Agonists; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways; D009687:Nuclear Proteins / Q000378:metabolism; D010835:Phytohemagglutinins; D010862:Pilocarpine; D017966:Pyramidal Cells / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism*; D013194:Staining and Labeling; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D018721:Muscarinic Agonists; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010835:Phytohemagglutinins; D010862:Pilocarpine; D018091:Receptors, AMPA; C492380:NeuN protein, mouse; C104723:glutamate receptor ionotropic, AMPA 3; C100156:leukoagglutinins, plants; C104722:glutamate receptor ionotropic, AMPA 2