Patterns of hippocampal neuronal loss and axon reorganization of the dentate gyrus in the mouse pilocarpine model of temporal lobe epilepsy.
The patterns of hippocampal neuronal loss and rewiring of the dentate gyrus (DG) were studied in the mouse model of temporal lobe epilepsy at 2 months after pilocarpine-induced status epilepticus (PISE). NeuN immunocytochemistry showed two patterns of neuronal damage, i.e., type 1 with partial loss of pyramidal neurons in CA3 area and type 2 with almost compete loss of CA3 pyramidal neurons. Anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) demonstrated that, at different rostrocaudal segments of the hippocampus, associational and commissural connections in the DG changed differently between mice with type 1 vs. type 2 neuronal loss. Calretinin (CR)-immunopositive mossy cells in ventral hilus and its fibers in inner molecular layer of bilateral DG remained in mice with type 1 but almost disappeared in mice with type 2 neuronal loss, which was further supported by retrograde labeling with cholera toxin subunit B (CTB) showing colocalization of CTB with CR in the ventral hilus of bilateral DG in mice with type 1 neuronal loss, which was lost in those with type 2 neuronal loss. Furthermore, the sprouted PHA-L-immunopositive en passant and terminal boutons from the DG were found in CA1 area to contact with surviving calbindin-, CR-, and parvalbumin-immunopositive neurons. The present study therefore suggests that different patterns of neuronal loss in CA3 area may be linked to different axon reorganizations in the DG.
Zhang
Si
S
Epilepsy Research Laboratory, National Neuroscience Institute, Singapore.
Khanna
Sanjay
S
Tang
Feng Ru
FR
D000818:Animals; D064032:Calbindin 2; D016923:Cell Death; D002772:Cholera Toxin; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D007150:Immunohistochemistry; D051379:Mice; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology* / Q000502:physiology / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000378:metabolism; D010835:Phytohemagglutinins; D010862:Pilocarpine; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012640:Seizures
C576511:Calb2 protein, mouse; D064032:Calbindin 2; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D010835:Phytohemagglutinins; D064030:S100 Calcium Binding Protein G; C100156:leukoagglutinins, plants; D010862:Pilocarpine; D002772:Cholera Toxin