Kainate treatment alters TGF-beta3 gene expression in the rat hippocampus.
In order to evaluate the role of transforming growth factor (TGF)-beta3 in the neurodegenerative process, we examined the levels of mRNA and immunocytochemical distribution for TGF-beta3 in the rat hippocampus after systemic kainic acid (KA) administration. Hippocampal TGF-beta3 mRNA level was reduced 3 h after KA injection. However, the levels of TGF-beta3 mRNA were elevated 1 day post-KA and lasted for at least 30 days. A mild TGF-beta3 immunoreactivity (TGF-beta3-IR) in the Ammon's horn and a moderate TGF-beta3-IR in the dentate granule cells were observed in the normal hippocampus. The CA1 and CA3 neurons lost their TGF-beta3-IR, while TGF-beta3-positive glia-like cells proliferated mainly throughout the CA1 sector and had an intense immunoreactivity at 7, 15 and 30 days after KA. This immunocytochemical distribution of TGF-beta3-positive non-neuronal populations was similar to that of glial fibrillary acidic protein (GFAP)-positive cells. Double labeling immunocytochemical analysis demonstrated colocalization of TGF-beta3- and GFAP-immunoreactivity in the same cells. These findings suggest a compensatory mechanism of astrocytes for the synthesis of TGF-beta3 protein in response to KA-induced neurodegeneration. In addition, exogenous TGF-beta3 (5 or 10 ng/i.c.v.) significantly attenuated KA-induced seizures and neuronal damages in a dose-related manner. Therefore, our results suggest that TGF-beta3 plays an important role in protective mechanisms against KA-induced neurodegeneration.
Kim
Hyoung-Chun
HC
Neurotoxicology Program, College of Pharmacy, Korea Institute of Drug Abuse, Kangwon National University, Chunchon 200-701, South Korea. kimhc@cc.kangwon.ac.kr
Bing
Guoying
G
Kim
Seong-Jin
SJ
Jhoo
Wang-Kee
WK
Shin
Eun-Joo
EJ
Bok Wie
Myung
M
Ko
Kwang Ho
KH
Kim
Won-Ki
WK
Flanders
Kathleen C
KC
Choi
Shin-Geon
SG
Hong
Jau-Shyong
JS
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048429:Cell Size; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology* / Q000633:toxicity; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D009457:Neuroglia / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012640:Seizures / Q000139:chemically induced; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053782:Transforming Growth Factor beta3
D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; C509046:Tgfb3 protein, rat; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D007608:Kainic Acid