ABSTRACT
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.
Subject(s)
Aging/metabolism , Brain Ischemia/metabolism , Hippocampus/metabolism , Nerve Degeneration/metabolism , Superoxide Dismutase/metabolism , alpha-Synuclein/metabolism , Aging/pathology , Animals , Brain Ischemia/physiopathology , Cell Death/drug effects , Cell Death/physiology , Disease Models, Animal , Down-Regulation/drug effects , Down-Regulation/physiology , Gerbillinae , Hippocampus/pathology , Hippocampus/physiopathology , Immunohistochemistry , Male , Nerve Degeneration/etiology , Nerve Degeneration/physiopathology , Protein Structure, Tertiary/physiology , Pyramidal Cells/drug effects , Pyramidal Cells/metabolism , Pyramidal Cells/pathology , Reactive Oxygen Species/metabolism , Reperfusion Injury/metabolism , Reperfusion Injury/physiopathology , Superoxide Dismutase/pharmacology , Time Factors , alpha-Synuclein/antagonists & inhibitors , alpha-Synuclein/chemistryABSTRACT
In the present study, we investigated chronological changes in Cu,Zn-superoxide dismutase (SOD1) immunoreactivity and its protein levels in the hippocampal CA1 region of adult and aged gerbils after transient forebrain ischemia to compare ischemia-related changes in SOD1 in adult and aged gerbils. Delayed neuronal death in the CA1 region at 4 days after ischemic insult was prominent in adult gerbils compared to that in aged gerbils. In sham-operated gerbils, SOD1 immunoreactivity and protein level in the aged group were significantly higher than that in the adult group. At 12 h after ischemia-reperfusion, SOD1 immunoreactivity and protein level were increased in both the groups. At 1 day after ischemia, SOD1 immunoreactivity and protein level in the adult group were significantly increased: the SOD1 immunoreactivity was increased in non-pyramidal cells as well as pyramidal cells. At this time after ischemia, SOD1 immunoreactivity and protein level in the aged group were decreased: the immunoreactivity was decreased significantly in pyramidal cells. At 4 days after ischemia, SOD1 immunoreactivity was detected only in non-pyramidal cells of the CA1 region in both the groups. These results suggest that SOD1 in the gerbil hippocampal CA1 region is higher in sham-aged group than that in sham adult one, and that different changes in SOD1 in CA1 pyramidal cells after ischemia in adult and aged gerbils may indicate different processes in delayed neuronal death with time after ischemic insult.
Subject(s)
Aging/metabolism , Brain Ischemia/enzymology , Cerebral Infarction/enzymology , Hippocampus/enzymology , Reperfusion Injury/enzymology , Superoxide Dismutase/metabolism , Aging/pathology , Animals , Brain Ischemia/physiopathology , Cell Death/physiology , Cerebral Infarction/pathology , Cerebral Infarction/physiopathology , Disease Models, Animal , Gerbillinae , Hippocampus/pathology , Hippocampus/physiopathology , Immunohistochemistry , Male , Nerve Degeneration/enzymology , Nerve Degeneration/etiology , Nerve Degeneration/physiopathology , Neurons/enzymology , Neurons/pathology , Oxidative Stress/physiology , Reperfusion Injury/physiopathology , Time Factors , Up-Regulation/physiologyABSTRACT
We examined alterations in Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) immunoreactivity following ischemia. Twelve hours after ischemia, NKCC1 immunoreactivity in the CA1 region and in the hilar region was significantly diminished. Twenty-four hours after ischemia, NKCC1 immunoreactivity was intensified in these hippocampal regions as well as CA2-3. Two days after ischemia, NKCC1 immunoreactivity in the CA1 and the hilar neurons had disappeared, although in the CA2-3 and the granule cell layer NKCC1 immunoreactivities had recovered to the sham level. This finding suggests that NKCC1 may play an important role in the ischemic neuronal injury induced by excitotoxicity as well as neuronal edema.
