Changes in the expression of the B subunit of vacuolar H+-ATPase, in the hippocampus, following transient forebrain ischemia in gerbils

Objective(s): Vacuolar H+-ATPase is a highly conserved enzyme that plays an important role in maintaining an acidic environment for lysosomal function and accumulating neurotransmitters in synaptic vesicles. In the present study, we investigated the time-dependent changes in the expression of vacuolar H+-ATPase V۱B۲ (ATP۶V۱B۲), a major neuronal subtype of vacuolar H+-ATPase located in the hippocampus, after ۵ min of transient forebrain ischemia in gerbils. We also examined the pH and lactate levels in the hippocampus after ischemia to elucidate the correlation between ATP۶V۱B۲ expression and acidosis.Materials and Methods: Transient forebrain ischemia was induced by occlusion of both common carotid arteries for ۵ min and animals were sacrificed at various time points after ischemia for immunohistochemical staining of ATP۶V۱B۲ and measurements of pH and lactate levels in the hippocampus.Results: ATP۶V۱B۲ immunoreactivity was found to be transiently increased in the hippocampal CA۱ region and dentate gyrus ۱۲–۲۴ hr after ischemia when the pH and lactate levels were decreased. In addition, ATP۶V۱B۲ immunoreactivity significantly increased in the hippocampal CA۳ and dentate gyrus, regions relatively resistant to ischemic damage, ۴ days after ischemia, when the NeuN-positive, mature neuron numbers were significantly decreased in the hippocampal CA۱ region. Conclusion: These results suggest that ATP۶V۱B۲ expression is transiently increased in the hippocampus following ischemia, which may be intended to compensate for ischemia-related dysfunction of ATP۶V۱B۲ in the hippocampus.

Keywords:

Acidosis , Cell death , Gerbils , Hippocampus , Ischemia