Effects of proteasome inhibitor MG132 on proliferation of neural stem cells in subventricular zone

AIM: To investigate the role of proteasome in the degeneration of neuron in age-related diseases such as Parkinson disease (PD) by observing the effects of proteasome inhibitor MG132 on the proliferation of neural stem cells (NSCs) in the subventricular zone (SVZ).METHODS: Stereotaxic microinjection of proteasome inhibitor MG132 at a dose of 10 μg into the left lateral ventricle of 90-day-old mice was performed.The control mice were received the same volume of DMSO into the left lateral ventricle.Three days, 7 days and 14 days after injection, the total proteins isolat from SVZ were subject to proteasome activity assay using the fluorescence microplate reader.Meanwhile, the mice were administered with 5-bromo-2'-deoxyuridine (BrdU) by intraperitoneal injection.The numbers of BrdU-positive cells were counted to examine the effect of MG132 on the proliferation of NSCs.RESULTS: After microinjection of MG132 into the left lateral ventricle, the proteasome activity in SVZ was significantly decreased on day 3 and day 7 post-injection (P<0.05) as compared with the control animals.Furthermore, the numbers of BrdU⁺ cells in SVZ were significantly reduced to 21±4 on day 3 and to 22±3 on day 7 post-injection (P<0.05).After long periods of treatment with MG132, the proteasome activity in SVZ was restored to normal level on day 14 post-injection.At the same time, no statistical difference of BrdU⁺ cells between the mice treated with MG132 (82±4) and DMSO (67±6) was observed (P>0.05).CONCLUSION: Short-term injection of reversible proteasome inhibitor MG132 attenuates the proteasome activity in SVZ, which in turn inhibits the proliferation of NSCs, suggesting that the proteasome activity may be closely related to the proliferation potential of NSCs.