Comparison of alpha-synuclein immunoreactivity and protein levels in ischemic hippocampal CA1 region between adult and aged gerbils and correlation with Cu,Zn-superoxide dismutase.
In this study, we examined changes in the level and immunoreactivity of alpha-synuclein in the hippocampal CA1 region of adult (6 months old) and aged (24 months old) gerbils after 5 min of transient forebrain ischemia. The delayed neuronal death of CA1 pyramidal cells in adult gerbils was severer than that in aged gerbils 4 days after ischemia/reperfusion. Alpha-synuclein immunoreactivity in the CA1 region of adult and aged gerbils significantly changed after ischemia. In control animals, alpha-synuclein immunoreactivity and level in the aged-gerbil CA1 region were higher than those in the adult-gerbil CA1 region. In both adult and aged gerbils, alpha-synuclein immunoreactivity and level started to increase 3h after ischemia, and they were highest 1 day after ischemia. Thereafter, alpha-synuclein immunoreactivity and level decreased with time after ischemia. We also observed the effects of Cu,Zn-superoxide dismutase (SOD1) on ischemic damage using the Pep-1 transduction domain. Alpha-synuclein level in the CA1 region was lower in Pep-1-SOD1-treated adult and aged gerbils than in vehicle-treated adult and aged gerbils. We conclude that neuronal loss in the hippocampal CA1 region of adult gerbils was more prominent than that in aged gerbils 4 days after ischemia/reperfusion. The higher level of alpha-synuclein in the aged-gerbil CA1 region than that in the adult-gerbil CA1 region may be associated with the earlier induction of reactive oxygen species, and Pep-1-SOD1 potentially and reversibly inhibits the accumulation of alpha-synuclein in the CA1 region after transient ischemia.
Yoon
Dae-Kun
DK
Department of Surgery, College of Medicine, Hallym University, Chuncheon 200-702, South Korea.
Hwang
In Koo
IK
Yoo
Ki-Yeon
KY
Lee
Yoon-Bok
YB
Lee
Jae-Jung
JJ
Kim
Jong-Hyun
JH
Kang
Tae-Cheon
TC
Lee
Bong-Hee
BH
Sohn
Heon-Soo
HS
Won
Moo Ho
MH
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D017434:Protein Structure, Tertiary / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors; D051844:alpha-Synuclein / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
D017382:Reactive Oxygen Species; D051844:alpha-Synuclein; D013482:Superoxide Dismutase