@article{57a8922ff96c408daf1decfb4baf087c,
title = "Cell density increases Bcl-2 and Bcl-x expression in addition to survival of cultured cerebellar granule neurons",
abstract = "The proto-oncogene bcl-2 and its family members, bcl-x and bax are recognized as major regulators of cell death and survival. Although Bcl-2 and Bcl-x are expressed in brain, little is known how they are regulated in neurons. Here we have studied the expression of bcl-2, bcl-xL and bax mRNA in rat cerebellar granule neurons cultured under conditions which influence neuron survival. Insulin-like growth factor-1 and brain-derived neurotrophic factor supported the survival of these neurons, but affected neither the expression of bcl-2, bcl-xL nor bax mRNA. In contrast, bcl-2 and bcl-xL mRNAs were up-regulated in cerebellar granule neurons plated at high density exhibiting an increased neuronal survival. Western blots showed that cell density also increased Bcl-2 protein level. However, conditioned medium from dense cultures did not affect the level of bcl-2 mRNA nor survival of the neurons. This suggests that cell density promotes survival and regulates Bcl- 2 expression in cerebellar granule neurons through a signaling pathway different from known neurotrophic factors.",
keywords = "BDNF, Bcl-2, bcl-x, cell density, cerebellar granule neurons, gene regulation",
author = "Y. Ohga and U. Zirrgiebel and S. Hamn{\'e}r and Michaelidis, {T. M.} and J. Cooper and H. Thoenen and D. Lindholm",
note = "Funding Information: Taken together the present results show that granule neuron survival is affected by two, possible different intracellular pathways. Neurotrophic molecules such as IGF-I and BDNF promote neuron survival but this does not involve an increase in bcl-2 or bcl-xL expression. On the other hand, cell density increases survival and upregulates the levels of bcl-2 and bcl-xL in the granule neurons. In vivo, cerebellar granule neurons are tightly packed in the internal granule layer, and cell-cell contact may support their survival even in the absence of neurotrophic factors. The mechanism(s) by which increased density enhances expression of bcl-2 family members in neurons remain to be explored but specific integrin molecules were recently shown to up-regulate Bcl-2 in Chinese hamster ovary cell lines. 25 Aeknowledgements--Y. O. is an Alexander von Humboldt-Stiftung fellow. S. H. was supported by the Swedish Cancer Society, and T. M. M. and J. C. were supported by a grant from Human Capital and Mobility.",
year = "1996",
month = aug,
doi = "10.1016/0306-4522(96)00204-7",
language = "English",
volume = "73",
pages = "913--917",
journal = "Neuroscience",
issn = "0306-4522",
number = "4",
}