Nerve growth factor withdrawal induces the apoptotic death of developing septal cholinergic neuronsvitro: Protection by cyclic AMP analogue and high potassium

doi:10.1016/0306-4522(95)00365-7

Neuroscience

Volume 70, Issue 2, January 1996, Pages 329-339

https://doi.org/10.1016/0306-4522(95)00365-7 Get rights and content

Abstract

Nerve growth factor regulates the developmental programmed cell death of certain neurons in the peripheral nervous system. The functions of nerve growth factor in the central nervous system are less well characterized. Nerve growth factor withdrawal results in the protein synthesis-dependent death of a large percentage of developing septal cholinergic neurons in sandwich tissue culture. In this study double labelling techniques were used to demonstrate that septal cholinergic neurons subjected to nerve growth factor withdrawal exhibit condensed chromatin and fragmented nuclei, and are labelled intensely for fragmented DNA. These degenerative changes are characteristic of apoptotic cell death. Half of the cholinergic neurons were committed to die and could no longer be rescued by nerve growth factor reapplication following approximately 16.5 h of nerve growth factor deprivation, whereas half of the cholinergic neurons could no longer be rescued by cycloheximide addition after only 9 h of nerve growth factor deprivation, suggesting that nerve growth factor and cycloheximide effect rescue by distinct mechanisms. Addition of a cyclic AMP analogue or depolarization with high K⁺, but not the general nuclease inhibitor aurintricarboxylic acid, prevented the death of cultured septal cholinergic neurons subjected to nerve growth factor withdrawal. Furthermore, these agents are capable to rescuing cholinergic neurons subjected to a period of nerve growth factor withdrawal after which addition of cycloheximide is no longer protective. Thus, nerve growth factor, cyclic AMP and high K⁺ can effect rescue after inhibition of translation ceases to be protective.

These findings suggest that under defined conditionsin vitro, withdrawal of nerve growth factor from septal cholinergic neurons during a critical period of development results in the apoptotic death of these CNS neurons, which can be prevented at the post-translational level by nerve growth factor, cyclic AMP and high K⁺.

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Nerve growth factor withdrawal induces the apoptotic death of developing septal cholinergic neuronsvitro: Protection by cyclic AMP analogue and high potassium

Abstract

Neuron

Neuron

Expl Neurol.

Cell

Trends Neurosci.

J. biol. Chem.

Neuroscience

Devl Brain Res.

Seminars Neurosci.

Neurosci. Lett.

Neuron

Neuron

Biochim. biophys. Acta

Trends Neurosci.

Int. Rev. Cytol.

Brain Res.

Fedn. Eur. Biochem. Socs Lett.

Aurintricarboxylic acid rescues PC12 cells and sympathetic neurons from cell death caused by nerve growth factor deprivation: correlation with suppression of endonuclease activity

J. Cell Biol.

Developmental cell death: morphological diversity and multiple mechanisms

Anat. Embryol. Berl.

Death of septal cholinergic neurons following ablation of target neurons in neonatal rats

Soc. Neurosci. Abstr.

Nerve growth factor withdrawal induces the apoptotic death of developing septal cholinergic neurons_vitro: Protection by cyclic AMP analogue and high potassium