Prolactin induces MAPK signaling in neural progenitors without alleviating glucocorticoid-induced inhibition of in vitro neurogenesis.
We recently demonstrated that prolactin (PRL) prevents chronic stress-induced inhibition of adult hippocampal neurogenesis. It remained unsettled, however, whether PRL is acting directly on neural stem and progenitors cells (NPCs) or if neurogenesis is affected by an indirect mechanism, for example through the extensively described effects of PRL on the HPA axis. To address this point, we used neurosphere cultures derived from the adult rat hippocampus as an in vitro model for NPCs. Dexamethasone (DEX) was applied to stress the NPCs, and proliferation, survival and differentiation of cells were examined. DEX markedly inhibited proliferation of NPCs and cells entered the G(0) phase of cell cycle. Moreover, DEX reduced NPC survival and repressed astroglial differentiation, which is normally induced by serum or bone morphogenetic protein application. Even though we could demonstrate that NPCs express the PRL receptor and ERK1/2 signaling is induced by PRL, we did not observe any effect of PRL on NPCs proliferation, differentiation or survival, neither in the presence nor during absence of DEX. In summary, our results indicate that PRL action on NPCs and neurogenesis in vivo occurs via an indirect mechanism.
Wagner
Katrin
K
Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, Austria.
Couillard-Despres
Sebastien
S
Lehner
Bernadette
B
Brockhoff
Gero
G
Rivera
Francisco J
FJ
Blume
Annegret
A
Neumann
Inga
I
Aigner
Ludwig
L
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D011388:Prolactin / Q000494:pharmacology*; D051381:Rats; D011981:Receptors, Prolactin / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D013234:Stem Cells / Q000166:cytology*
D005938:Glucocorticoids; D011981:Receptors, Prolactin; D003907:Dexamethasone; D011388:Prolactin; D048052:Mitogen-Activated Protein Kinase 3