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Regeneration of granule neurons after lesioning of hippocampal dentate gyrus: Evaluation using adult mice treated with trimethyltin chloride as a model
Author(s) -
Ogita Kiyokazu,
Nishiyama Norito,
Sugiyama Chie,
Higuchi Kei,
Yoneyama Masanori,
Yoneda Yukio
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20678
Subject(s) - dentate gyrus , subgranular zone , neurogenesis , neun , doublecortin , granule cell , hippocampal formation , neuroscience , neural stem cell , nestin , biology , chemistry , microbiology and biotechnology , stem cell , immunology , subventricular zone , immunohistochemistry
The hippocampal dentate gyrus in adult animals is known to contain neural progenitors that proliferate and differentiate into neurons in response to brain injury. Little has been observed, however, on regeneration of the granule cell layer of the dentate gyrus that has been directly injured. Using trimethyltin (TMT)‐treated mice as an in vivo model, we evaluated the ability of this layer to regenerate after injury. The administration of TMT induced neuronal death in the dentate gyrus selectively 2 days later, with recovery of granule neurons on day 14 and thereafter. At an early stage (days 2–5) after the damage by TMT treatment, 5‐bromo‐2′‐deoxyuridine (BrdU) incorporation into at least two different types of cells was facilitated in the dentate gyrus: BrdU‐positive/neuronal nuclear antigen (NeuN)‐negative cells were found predominantly in the subgranular zone and granule cell layer, whereas BrdU‐positive/NeuN‐positive cells were numerous in the dentate molecular layer and hilus. In addition, expression of proliferating cell nuclear antigen, nestin, NeuroD3, and doublecortin, which are markers for proliferating cells and neural progenitors/neuronal precursors, was extremely enhanced in the dentate gyrus at the early stage after treatment. Double staining revealed that BrdU was colocalized with nestin and doublecortin in the subgranular zone. Behavioral analysis revealed that TMT‐induced cognition impairment was ameliorated by day 14 after the treatment. Taken together, our data indicate that the hippocampal dentate gyrus itself is capable of regenerating the neuronal cell layer through rapid enhancement of neurogenesis after injury. © 2005 Wiley‐Liss, Inc.