·To explore whether 6-hydroxydopamine(6-OHDA)-induced Parkinson disease (PD) mouse models have senescent phenotypes and explore the changes of senescence-related glial cells.

·Thirty 9?10 months old C57BL/6J male mice were divided into Sham-operated group (n=15) and 6-OHDA group (n=15). PD mouse models were established by stereotactic injection of 6-OHDA into striatum. The neurological function deficit was evaluated by rotarod test and apomorphine (APO)-induced rotational behavior on the 21st day after modeling. The brain was taken after the last behavioral experiment. Western blotting was used to detect the protein content of tyrosine hydroxylase (TH) in both caudate putamen (CPu) and substantia nigra (SN) regions. Immunofluorescence was used to observe the expression of glial cells and aging marker p16^Ink4a / p21 in both CPu and SN regions. RT-qPCR was also used to detect the expression and changes of cyclin-dependent kinase inhibitor including p16^Ink4a, p15^Ink4b, p19^Ink4d, p21 and p27^Kip1, and senescence-associated secretory phenotype including Cxcl10, Ccl2, tumor necrosis factor-α (Tnf-α), interleukin-1α (Il-1α), Il-1β, Il-6 and matrix metalloproteinase 3 (MMP3).

·The decreased falling latency in rotarod test (P=0.000), the increased number of rotations induced by APO (P=0.000) and the loss of TH protein measured by Western blotting (P=0.000), suggested that 6-OHDA unilateral striatum mouse model of PD was successfully established. Immunofluorescence staining showed that the upregulation of an aging marker p16^Ink4a in both CPu and SN regions of the 6-OHDA group compared with the Sham group, but p21 was not significantly expressed in both groups; senescent astrocytes, microglia and oligodendrocytes were accumulated in CPu and SN regions as well, while the number of astrocytes was larger than the other two types of glia cells (P<0.05). RT-qPCR results showed that, compared with those of the Sham group, p15^Ink4b, p16^Ink4a and p19^Ink4d in CPu and SN regions of the 6-OHDA group were up-regulated (P<0.05); p21 was slightly up-regulated, but the difference was not statistically significant (P?0.05); p27^kip1 was slightly up-regulated, but statistically significant difference only presented in SN region (P=0.016). RT-qPCR also showed that, compared with those of the Sham group, the levels of Cxcl10, Ccl2, Il-1α and Il-6 were significantly up-regulated while Il-1β was significantly decreased in CPu region of the 6-OHDA group (P<0.05); the levels of Ccl2, Tnf-α, Il-1α and Il-6 were significantly increased while Mmp3 and Il-1β were significantly decreased in SN region of the 6-OHDA group (P<0.05).

·6-OHDA-induced PD mice exhibit senescent phenotypes characterized by upregulation of p16^Ink4a and astrocyte senescence.