Seizure-associated, aberrant neurogenesis in adult rats characterized with retrovirus-mediated cell labeling.
Seizure activity within the hippocampal circuitry not only affects pre-existing structures, but also dramatically increases the number of newborn granule cells. A retroviral strategy was used to label dividing cells and their progeny in the adult dentate gyrus and to analyze the impact of epileptic activity on adult-generated cells labeled before or after seizures. We show that epileptic activity led to dramatic changes in the neuronal polarity, migration, and integration pattern of newborn granule cells, depending on the time of birth in relation to the epileptic insult. Aberrant neurons were stably integrated into the dentate circuitry, and the consequences on hippocampal neurogenesis were long lasting. The data presented characterized the consequences of seizure-associated plasticity on adult neurogenesis leading to long-term structural changes in the hippocampal circuitry that might represent a pivotal component of the epileptic disease process.
Jessberger
Sebastian
S
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Zhao
Chunmei
C
Toni
Nicolas
N
Clemenson
Gregory D
GD
Li
Yan
Y
Gage
Fred H
FH
D000818:Animals; D001522:Behavior, Animal; D049109:Cell Proliferation / Q000187:drug effects; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D000089622:Doublecortin Domain Proteins; D005260:Female; D005822:Genetic Vectors / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D007608:Kainic Acid; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009479:Neuropeptides / Q000378:metabolism; D038081:Organogenesis; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012190:Retroviridae / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors
D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D016760:Proto-Oncogene Proteins c-fos; D049452:Green Fluorescent Proteins; D007608:Kainic Acid