One of the functions of Hh signaling is to promote adult neurogenesis, the process in which new neurons are born in the adult brain. Image on right shows neural progenitors labeled with the proliferation marker BrdU (purple) and FAPP7 (green) in the postnatal mouse hippocampus (image by Noriko Osumi from Tohoku Neuroscience Global). Adult neurogenesis is thought to be associated with brain plasticity and its defects may lead to depression and other neuropsychiatric disorders.
We studied the effects of the peptide PACAP, which blocks Hh signaling in other systems, on mouse adult neural progenitors. These cells grow in vitro as clonally-derived round clusters known as neurospheres (first image on left). We found that PACAP induces the attachment of neural progenitors to the substratum (second image), which indicates that it may regulate their adhesive or migratory potential.
Questions that we are trying to resolve:
What is the mechanism of the action of PACAP?
Does PACAP treatment change adult neural progenitor differentiation and proliferation potential?
Is this effect relevant for adult neurogenesis in vivo?