Purinergic Signaling Induce Proliferation Of Adult Olfactory Neural Stem Cells

Olfactory receptor neurons ( ORNs ) is a kind of special neuron in vertebrates. This particularity can be inferred from that: ORNs are the only neuron which keep its'soma so closely to the peripheral environment; The axons of ORNs is unmyelinated; Indifferent to other primary sensory neurons, Olfactory information transduced to the cortex directly. However, the most unique feature of ORNs is that it can be regenerate permanently throughout the adult life. ORNs are regenerated by the OE neural stem cells which reside in the basal region of the OE. The regenerable characteristic of ORNs makes the olfactory system as a good model to study the dynamics and regulation mechanism of stem cells.Olfactory neurogenesis can be classified into three different phases: embryonic establishment, from E10 to P0, postnatal expansion, from P1 to P30, and adult maintenance, from P30 to death. In every phase of olfactory neurogenesis, ORNs are differentiated from OE neural stem cells. In the OE, different phase have different stem cells, and they posses different regulation mechanism. In embryo development, olfactory system is originated from the olfactory placode. Olfactory placode emerges at E9.5, and at E10, olfactory placode invaginates and forms the olfactory pit. As the olfactory pit emerges, cells of the ORNs lineage have been differentiated out. At E14.5, Cells in the OE show the mutual characteristics and express the markers of OE cells. Many factors regulate the embryo olfactory neurogenesis, such as FGF8, GDF11 and transcription factors MASH1, Six1, SOX2 et al. During the adult hood, olfactory neurogenesis under more precisely controls. But the detailed mechanisms are still unknown. Apoptosised ORNs can activate the resided and migrated macrophages in the OE. Activated macrophages can release cytokines such as LIF, TGF-βand promote the proliferation of OE stem cells.Purins as a kind of signal molecular play an important role in the signal transduction of cells. Purinergic signals have been reported that it take part in the regulation of proliferation, differentiation and migration of stem cells. Purinergic signals can meditate the induction of HSP and play a neural protective role in the OE when ORNs are injured. Whether purinergic signals meditate the regulation of ORNs neural genesis remains to be clarified.Our researches have focused on the purinergic signals in the neural genesis of ORNs. Data show that purinergic receptors– P2X1, P2X2, P2X3 and P2X7 expressed in the basal region of OE in where are the OE stem cells reside. Olfactory bulbctomies can induce synchronization apoptosis of ORNs. Most of the ORNs apoptosised 4 days after OBX, and at the same time the macrophages reach they peak amount in the OE. After OBX, lumbar injection with the antagonists of purin receptors, Suramin and PPADS ( 50μmol/kg ) for 4 days, and label the proliferating cells with Brdu before mouse were killed. Statistic analyze of the Brdu positive cells of experimental group and control group show that puinergic signal antagonists can significantly inhibit the proliferation of OE stem cells after 4d OBX. Based on these results, we can conclude that purinergic signals can regulate the proliferation of OE stem cells, but more work is needed to clarify the mechanism of this process.