Alpha-MSH modulates hippocampal neural precursor cell proliferation and differentiation

L. CARNIGLIA; J. SABA; D. RAMIREZ; J. TURATI; F. LOPEZ COUSELO; C. CARUSO; D. DURAND; M. LASAGA

CORDOBA

Congreso; SANXXXIII Reunión Anual. de la. Sociedad Argentina de Investigación en Neurociencias.; 2018

SAN

Hippocampal neurogenesis is essential for learning and memory. Neural precursor cells (NPCs) in the subgranular zone of the hippocampal dentate gyrus proliferate and differentiate into either glial cells or dentate granule cells. Alpha-melanocyte-stimulating hormone (-MSH) improves learning and memory, neuronal survival and plasticity in models of neuroinflammation, brain ischemia and Alzheimer?s disease and is a mitogen for adult rat subventricular zone neural stem cells. Here, we studied the effect of [Nle4,D-Phe7]--MSH (NDP-MSH) on hippocampal NPC differentiation. Postanatal hippocampal NPCs were propagated in vitro as neurospheres. Cells were dispersed and cultured without growth factors. NDP-MSH was added on days 0 and 3. After 6 days in culture, a large proportion of NPCs become quiescent, evidenced by loss of nuclear Ki-67 expression. Treatment with NDP-MSH prevents the exit from cell cycle, increasing the proportion of Ki-67+/Nestin+ cells (putative type 2 precursors), and promotes cell proliferation evidenced by BrdU incorporation. In turn, there is a decrease in the expression of neuroblast marker DCX and in the proportion of NS-1+ cells (oligodendrocytes), as well as GFAP+/Ki-67- cells (putative astrocytes or quiescent type 1 precursors). Additionally, NDP-MSH stimulates microglial phagocytosis of dead neurons. To conclude, NDP-MSH modulates the hippocampal neurogenic niche by regulating NPC fate while acting on local microglia to promote clearance of dead cells.