Effect of nerve growth factor on proliferation of rat hippocampal astrocytes

CRAGNOLINI, ANDREA BEATRIZ; HUANG, YANGYANG; FRIEDMAN, WILMA J

Congreso; Society for Neuroscience Meeting; 2007

Society for Neuroscience

Nerve growth factor (NGF) is a pleiotropic factor that controls many aspects of development, growth, survival and death in the central nervous system. NGF acts through binding to two classes of cell surface receptors, the tyrosine kinase receptor A (TrkA) and p75NTR. The p75NTR has been shown to mediate the death of hippocampal neurons induced by neurotrophins and proneurotrophins. Hippocampal astrocytes express p75NTR but not TrkA, however its function has not been characterized. Our previous results had demonstrated that NGF reduces the number of cells in S phase of the cell cycle, nevertheless remains unclear if NGF inhibits or retards the proliferation of astrocytes. The cell cycle is regulated by a holoenzyme complex of cyclins and cyclin-dependent kinases (cdks) that phosphorylate and inactivate the retinoblastoma protein, which then facilitates progression through the G1/S restriction point of the cell cycle. In addition, two families of cdk-inhibitory proteins, the Ink4s and the Cip/KIPs, inhibit holoenzyme activity and cell cycle progression. Previous results from our laboratory have shown that NGF increases the association of p75 and SC1 and inhibits cyclin E production in hippocampal astrocytes. In this study, we have examined the effect of NGF on cell cycle regulators such as cyclins, cdks and their inhibitors that may occur during the suppression of cell-cycle progression of hippocampal astrocytes cultures.