title: Degeneration and regeneration of GABAergic interneurons in the dentate gyrus of adult mice in experimental models of epilepsy.
abstract: OBJECTIVE
  Mounting evidence showed that GABAergic interneurons play an important role in the generation of seizures by regulating excitatory/inhibitory balance in the hippocampus; however, there is a continuous debate regarding the alteration in the number of hippocampal GABAergic interneurons during epileptogenesis. Here, we investigated the degeneration and regeneration of GABAergic interneurons in the dentate gyrus during epileptogenesis using glutamic acid decarboxylase-green fluorescence protein (GAD67-GFP) knock-in mice.
  
  
  RESULTS
  Pentylenetetrazol (PTZ)-induced chronic kindling model and lithium-pilocarpine-induced status epilepticus (SE) model were used in this study. We found a progressive loss of GABAergic interneurons in the dentate gyrus during post-SE epileptogenesis rather than PTZ kindling. Both types of epileptogenic insults significantly promoted the proliferation of neural progenitor cells in the dentate gyrus; however, compared to 80% neuronal differentiation ratio in the control group, there was a remarkable decrease in PTZ kindling and pilocarpine models, that is 58% and 29%, respectively. Double/triple immunofluorescence labeling revealed no newborn neurons colabeled with GFP in both intact and epileptic dentate gyrus. In addition, valproate (a first-line antiepileptic drug) treatment prevented the loss of GABAergic interneurons but still failed to induce the regeneration of GAD67-positive interneurons in the dentate gyrus during post-SE epileptogenesis.
  
  
  CONCLUSIONS
  These results indicate that degeneration of GABAergic interneurons may depend on the type of epileptogenic insult and that no newborn GABAergic interneurons occur in the adult dentate gyrus during epileptogenesis.
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wei
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Sheng-Xi
authors.initials: SX
authors.lastname: Wu
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002908:Chronic Disease; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology*; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology*; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D007696:Kindling, Neurologic; D018020:Lithium Compounds; D008297:Male; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D010433:Pentylenetetrazole; D010862:Pilocarpine; D013226:Status Epilepticus; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D018020:Lithium Compounds; D010862:Pilocarpine; D049452:Green Fluorescent Proteins; D014635:Valproic Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D010433:Pentylenetetrazole
keywords: Epilepsy; GABA; Green fluorescence protein; Hippocampus; Neurogenesis