Journal of Cell Science & Therapy
Open Access
ISSN: 2157-7013
+44 1300 500008
ISSN: 2157-7013
+44 1300 500008
Bianca Marchetti
University of Catania Medical School, Italy
OASI Institute for Research and Care on Mental Retardation and Brain Aging, Italy
Posters & Accepted Abstracts: J Cell Sci Ther
Within their specialized germinal niches, populations of local astrocytes instruct neural stem/progenitor cells (NSCs) via. complex cell-cell interactions and signaling cascades, which include the activation of the Wnt/�²-catenin pathway, a signalling system required for specification and neurogenesis of midbrain dopaminergic (mDA) neurons, the pivotal neuronal population that degenerates in Parkinsonâ��s disease (PD) and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Recently, we uncovered that the midbrain aqueduct (Aq)-periventricular regions (PVRs) SVZ act as a natural niche for mDA progenitors. Accordingly, mDA neuron death induced by the neurotoxin MPTP, promotes an early astrocyte-dependent activation of these Aq- PVR-DA progenitors, but a lack of appropriate niche environmental signals restrict their neurogenic potential and compromise neuronal survival/rescue. Given that transplanted NSCs possess intrinsic capacity to ameliorate the injured microenvironment and to rescue dysfunctional neurons, here we used adult green fluorescent protein (GFP)+ NSCs as a graft source for unilateral transplantation above the subtantia nigra (SN) of MPTP mice. Remarkably, grafted GFP-NSC survived within the SN, in situ. Spatio-temporal analyses showed a significant protection/restoration of SN-TH+ cell bodies. Additionally, GFP+-NSCs were seen to accumulate at the Aq-SVZ niche, where they induced a profound remodelling of host GFAP+ astrocytes and �²-catenin over-expression thus suggesting activation of astrocyte-dependent Wnt signaling. Increased �²-catenin expression was also observed in SN-repairing neurons together with a robust striatal reinnervation, thereby uncovering a critical role of NPC crosstalk with the host niche and DA neurons via astrocytes for DA neuroprotection and neurorestoration, with implications for cell-based therapies for PD.
Email: biancamarchetti@libero.it