Cyclic AMP Elevation Is Sufficient to Promote the Survival of Spinal Motor NeuronsIn Vitro

Abstract

The short-term survival of highly purified embryonic spinal motor neurons (SMNs) in culture can be promoted by many peptide trophic factors, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), fibroblast growth factor (FGF), glial-derived neurotrophic factor (GDNF), and hepatocyte growth factor (HGF). We have asked whether these peptides are sufficient to promote the long-term survival of purified E15 SMNs. Contrary to previous reports, we find that when SMNs are cultured in serum-free medium containing a single peptide trophic factor only approximately one-third of the cells survive for 3 d in culture. When multiple factors are combined, additive effects on survival are observed transiently, but by 7 d of culture the majority of SMNs has died. Surprisingly, when cAMP levels are elevated, the majority of SMNs extend processes and survive for 1 week in culture in the absence of peptide trophic factors, even in low-density cultures. A combination of five peptide trophic factors, together with cAMP elevation, promotes the long-term survival of most of the SMNs in serum-free culture for 3 weeks. These findings provide useful culture conditions for studying the properties of SMNs and have implications for the treatment of motor neuron diseases.

Neuroprotective Function of the PGE2EP2 Receptor in Cerebral Ischemia

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Cyclic AMP Induces Transactivation of the Receptors for Epidermal Growth Factor and Nerve Growth Factor, Thereby Modulating Activation of MAP Kinase, Akt, and Neurite Outgrowth in PC12 Cells

“…Cyclic AMP can induce biological responses such as neuronal survival or differentiation on its own or it can potentiate the effects of RTKs (13)(14)(15). In PC12 cells, elevation of [cAMP] i induces morphological changes similar to NGF and survival in serum-free media (16,17).…”

GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism

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