The Neuroprective And Therapeutic Effects Of Inosine On MPTP-induced Parkinson's Disease In C57BL Mice

Parkinson's disease(PD) is a common neurodegenerative disorder in clinic.It is characterized by a selective loss of dopaminergic neurons in the substantia nigra and result in a decrease of dopamine(DA) in the substantia nigra to striatum path,which associated with a series of motor functional impairment.The exact cause of this neuronal loss is still unknown,but it has been known by now that several factors,such as generation and enviroment,are correlated with PD. l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine(MPTP),a neurotoxin that selectively damages dopaminergic cells in the substantia nigra,can induce a syndrome and pathologic changes similar to PD in mice.So it has been used to generate an useful animal model in PD studing. Inosine, one of the catabolic products of purine nucleotide, has long been clinically used to supplementally treat a variety of diseases due to its involvement in energy synthesis. Recently, it has been reported that inosine also plays an important protective and trophic role in the impairment and reparament of center nervous system. This study aimed to explore the neuroprective and therapeutic effects of inosine on MPTP-induced PD in C57BL mice. The PD models were formed with intraperitoneal injections of MPTP. Inosine was administered intraperitoneally to mice prior or after to MPTP. The effects ofinosine which was given prior or after MPTP on behavioral exhibition, number of dopaminergic neurons in the substantia nigra and density of tyrosine hydroxylase-immunoreactive(TH-ir) nerve fibers in the striatum, level of DA in the striatum were studied by behavioral test(score of locomotion,Rotarod test and swim test), immunohistochemical analysis and fiuorospectrophotometry.We found that the score of locomotion and Rotarod and swim test were declined about 45 % and 43 % and 22 % .The number of dopaminergic neurons in the substantia nigra were declined about 58%. The density of TH-ir nerve fibers were also showed thin. The level of DA in the striatum were declined about 88%.But inosine which administered prior to MPTP attenuated the neurotoxic effects of MPTP. The score of locomotion and Rotarod and swim test were declined only about 5% and 11% and 12 % .The number of dopaminergic neurons in the substantia nigra were declined only about 43 %. The level of DA in the striatum were declined only about 71 %.There is a significant difference in two groups(P<0.01);In another part of study, the twenty MPTP-induced PD mice were divided into saline group and inosine group randomly each ten. Inosine was continuously administered to mice four weeks. As what we have described above,the effect of inosine on behavioral exhibition, number of dopaminergic neurons in the substantia nigra and density of TH-ir nerve fibers in the striatum, level of DA in the striatum were studied by behavioral test, immunohistochemical analysis and fluorospectrophotometry. We found that there is no significant difference in the behavioral activity and number of dopaminergic neurons in the substantia nigra. But comparing to saline,the density of TH-ir nerve fibers and level of DA in the striatum were higher in inosine group. The level of DA in the striatum of inosine group were 2.08 times to saline. There is a significant difference in two groups(P < 0.01).The results suggest that inosine is...