ABSTRACT
Objective To observe the changes of dopamine and its metabolites,melatonin,as well as melatonin receptors in the substantia nigras (SN) in 6-OHDA induced hemiparkinsonian rats.Methods PD rat was established by a unilateral injection of 6-OHDA into the right substantia nigra pars compacta and medial forebrain bundle.Rats were divided into PD groups and vehicle groups,and sacrificed at 10:00 and 22:00 respectively,at 3 and 6 weeks post-lesion.The contents of dopamine and its metabolites as well as melatonin were measured by HPLC.The expressions of MT1 and MT2 mRNA and protein were detected by RT-PCR and Western-Blot respectively.Results Dopamine levels declined by 83％ and 88％ respectively at 3 and 6 weeks post-lesion in the injected side of PD rats,compared with the contralateral side.Melatonin levels in the injected side increased by 22％ and 29％ respectively.However,melatonin increased by 46％ and 31％ respectively at 10:00 and 22:00,at 6 weeks post-lesion in the contralateral side,compared with the same side of the vehicle.The expressions of MT1 and MT2 receptors mRNA were significantly decreased by 91.04％ and 90.24％ respectively in comparison with the vehicle,while the protein expression of MT1 and MT2 receptors significantly declined by 58％ and 70％ respectively.Conclusion Increased melatonin and down-regulated MT1 and MT2 receptors in the lesioned SN in 6-OHDA-induced rats may be associated with the progression of PD.
ABSTRACT
Objective To investigate dynamic changes in extracellular striatal 5-hydroxy indole acetic acid (5-HIAA) and melatonin (MLT) concentrations in the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) rat models.Methods A hemiparkinsonium rat model was established by a unilateral injection of 6-OHDA into the right substantia nigra pars compacta (SNc) and the right medial forebrain bundle (MFB).Dialysate samples were collected at 10:00 in the lesioned striatum by microdialysis at 1,2,3 and 4 weeks post-lesion,respectively.The levels of dopamine (DA) and 5-HIAA,as well as MLT in dialysate sanples were measured by high performance liquid chromotorgraphy (HPLC).Results One week after surgery,the level of DA in PD group was (1.19±0.22) ng/ml,which was distinctly lower than those in the vehicle group ((8.62 ± 0.73) ng/ml) and the sham group ((8.73 ± 0.78) ng/ml) (P ＜ 0.01).The levels of 5-HIAA in PD group had a downward trend,but there were no significant differences.The level of MLT in PD group was (43.31 ± 11.37) pg/ml at 4 weeks post-lesion,and significantly higher than those in the vehicle group ((19.13 ± 5.38)pg/ml) and the sham group ((19.80 ± 6.96) pg/ml) (P＜ 0.05).The striatal dialysate DA and 5-HIAA concentrations had a good positive correlation in the PD group (r =0.867,P ＜ 0.01).Conclusion Decreased DA level concomitantly with changes of 5-HIAA and MLT in the ipsilateral striatum of 6-OHDA-induced PD rats,and these changes may be related to PD progression.