Characterization of cyclin D1 expression in a rat global model of cerebral ischemia

Abstract

During normal development of the central nervous system there is expression of cyclins that regulate the progression of cells through various stages of mitosis. Cyclins have also been implicated in neuronal degeneration and apoptosis in adult brain, especially cyclin D1 as it is permissive for the transition from growth phase to synthesis phase in mitotic cell division. There is controversy as to whether cyclin D1 expression increases in both in vitro and in vivo models of cerebral ischemia. In this study we use immunohistochemistry and Western blot analysis to characterize cyclin D1 expression in an in vivo rat global model of cerebral ischemia to address the hypothesis that cyclin D1 alterations are involved in ischemic neuronal death. Although there was no change in cyclin D1 expression in either the vulnerable CA1 or resistant CA3 regions of the hippocampus prior to neuronal cell death (<3 days reperfusion), concomitant with the death of CA1 neurons and the loss of cyclin D1 in these cells, there was an increase in non-neuronal cyclin D1 positive cells. Some of the non-neuronal cyclin D1 expressing cells were identified to be activated microglia. In contrast to the cytoplasmic expression of cyclin D1 in neurons, the cyclin D1 expression in the microglia and other non-neuronal cells in CA1 was both nuclear and cytosolic. This study suggests that cyclin D1 does not play a role in the death of vulnerable CA1 neurons in global ischemia.