Loss of cyclin D1 in necrotic and apoptotic models of cortical neuronal degeneration

Recent evidence suggests that apoptosis in post-mitotic neurons involves an aborted attempt of cells to re-enter the cell cycle and it is characterize d by increased expression of cyclins, such as cyclin D1, prior to death. Cy clin D1 increases to permit transition from growth phase (G0/G1) to synthes is phase (S) during normal development but there is controversy its to whic h of the cyclins are activated prior to apoptotic cell death. Pie looked at the expression of cyclin D1 in cortical neuronal cultures treated with eit her staurosporine to produce apoptotic death, or with glutamate, to produce a non-apoptotic death. Cyclin D1 immunoreactivity was observed in the cyto plasm. and nucleus of virtually all neurons under control conditions. Follo wing the addition of either staurosporine or glutamate, cyclin D1 immunorea ctivity did not change within 4 h. The cyclin D1 immunoreactivity was lost by 6 h with the appearance of either staurosporine-induced fragmented nucle i or glutamate-induced pyknotic nuclei. These immunocytochemical observatio ns were confirmed with immunoblot analysis. Therefore, cyclin D1 is not a r eliable indicator of apoptosis in cortical neuronal cultures and should not be used as an indicator of apoptotic cell death. (C) 1999 Elsevier Science B.V. All rights reserved.