Epileptogenic roles of astroglial death and regeneration in the dentate gyrus of experimental temporal lobe epilepsy.
Recent studies have demonstrated that blockade of neuronal death in the hippocampus cannot prevent epileptogenesis in various epileptic models. These reports indicate that neurodegeneration alone is insufficient to cause epilepsy, and that the role of astrocytes in epileptogenesis should be reconsidered. Therefore, the present study was designed to elucidate whether altered morphological organization or the functionalities of astrocytes induced by status epilepticus (SE) is responsible for epileptogenesis. Glial responses (reactive microgliosis followed by astroglial death) in the dentate gyrus induced by pilocarpine-induced SE were found to precede neuronal damage and these alterations were closely related to abnormal neurotransmission related to altered vesicular glutamate and GABA transporter expressions, and mossy fiber sprouting in the dentate gyrus. In addition, newly generated astrocytes showed down-regulated expressions of glutamine synthase, glutamate dehydrogenase, and glial GABA transporter. Taken together, our findings suggest that glial responses after SE may contribute to epileptogenesis and the acquisition of the properties of the epileptic hippocampus. Thus, we believe that it is worth considering new therapeutic approaches to epileptogenesis involving targeting the inactivation of microglia and protecting against astroglial loss.
Kang
Tae-Cheon
TC
Department of Anatomy, College of Medicine, Hallym University, Chunchon, Kangwon-Do, South Korea. tckang@hallym.ac.kr
Kim
Duk-Soo
DS
Kwak
Sung-Eun
SE
Kim
Ji-Eun
JE
Won
Moo Ho
MH
Kim
Dae-Won
DW
Choi
Soo-Young
SY
Kwon
Oh-Shin
OS
D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D016923:Cell Death; D018891:Dentate Gyrus / Q000473:pathology*; D004833:Epilepsy, Temporal Lobe / Q000473:pathology* / Q000503:physiopathology; D005110:Extracellular Space / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000503:physiopathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D017628:Microglia / Q000473:pathology; D019599:Mossy Fibers, Hippocampal / Q000473:pathology; D009410:Nerve Degeneration / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology