Granule cell dispersion develops without neurogenesis and does not fully depend on astroglial cell generation in a mouse model of temporal lobe epilepsy.
OBJECTIVE
Granule cell dispersion (GCD) appears as a characteristic morphological feature of the mesial temporal lobe epilepsy (MTLE). It has been suggested that this phenomenon could be due to an increased neurogenesis in the dentate gyrus. However, this hypothesis is still debated and recent clinical and experimental studies have shown that neurogenesis is rather decreased in MTLE. To further determine the role of neural and astroglial cell generation in GCD we examined the consequences of aging and irradiation, which are known to reduce progenitor cells, in a mouse model of MTLE induced by intrahippocampal kainate (KA) injection.


METHODS
We injected KA in hippocampus of three different types of mice; (1) young adult, (2) aged, and (3) irradiated mice. Newly generated cells were labeled by Bromodeoxyuridine (BrdU) and were characterized by immunohistochemistry. The extent of GCD was compared among the three animal groups.


RESULTS
In young adult mice, BrdU-labeled neurons as well as doublecortin- and NeuroD-positive cells decreased progressively after KA injection whereas BrdU-labeled astrocytes and microglias increased. In aged and irradiated mice, where basal neurogenesis was already strongly reduced, GCD developed after KA injection to the same extent as in young adult mice. However, augmentation of the BrdU-labeled astrocytes after KA was less than 40% in irradiated mice in comparison to young and aged mice.


CONCLUSIONS
Our data show that GCD occurs without neurogenesis. Furthermore GCD developed regardless of the degree of astroglial cell proliferation, suggesting that neural stem cell generation is not crucial for GCD.
Nitta
Naoki
N
Department of Neurosurgery, Shiga University of Medical Science, Seta-Tsukinowa-Cho, Otsu, Shiga, Japan.
Heinrich
Christophe
C
Hirai
Hisao
H
Suzuki
Fumio
F
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009479:Neuropeptides / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011827:Radiation; D018709:Statistics, Nonparametric; D013997:Time Factors
D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C528900:glial fibrillary astrocytic protein, mouse; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine; D007608:Kainic Acid