Blood Vessels Say NO to Axons
Giti Garthwaite, Katalin Bartus, Denise Malcolm, David Goodwin, Martha Kollb-Sielecka, Chaminda Dooldeniya, and John Garthwaite
This week, Garthwaite et al. identify a nitric oxide (NO) signaling pathway from microvascular endothelial cells to axons. The authors made extracellular "grease-gap" recordings from isolated rat optic nerve in vitro to test components of the pathway. The exogenous NO donor with the intriguing name of PAPA/NO [(Z)-1-N-(3-ammoniopropyl)-N-(n-propyl)-amino]/NO] caused a few millivolt axonal depolarization. Inhibitors of NO synthase hyperpolarized the axons, suggesting that endogenous NO can activate the pathway. The source was endothelial nitric oxide synthase (eNOS) because optic nerves from mice lacking eNOS lacked tonic levels of NO and the associated depolarization. Immunostaining revealed eNOS in microvascular endothelial cells and cGMP in axons. Hyperpolarization-activated cyclic nucleotide-gated channels are a likely, but not necessarily the only, downstream target of NO-generated cGMP. At least under the conditions of these experiments, the pathway showed tonic activity, suggesting a potentially regulatory coupling between capillaries and neural activity.
Life and Death in the Basal Forebrain
Marta Volosin, Wenyu Song, Ramiro D. Almeida, David R. Kaplan, Barbara L. Hempstead, and Wilma J. Friedman
The p75 neurotrophin receptor (p75NTR) and Trk receptor tyrosine kinases elicit opposite cellular consequences: apoptosis and survival, respectively. This week, Volosin et al. compared the actions of proneurotrophins, selective activators of p75NTR, with neurotrophins on basal forebrain neurons. These cholinergic neurons express p75NTR throughout life as well as all three Trk receptors. The results suggest that Trk receptor activation cannot overcome apoptosis triggered by activation of p75
Contact: Sara Harris
Society for Neuroscience