Relationships Between The Retina-midbrain-striatum-Pineal Gland Axis And Parkinson's Disease

Objective:1,To investigate the relationship between melatonin (MLT) levels and dopamine(DA) levels in the striatum and substantia nigra of hemiparkinsonium rats.2,To investigate the relationship between MLT levels and DA levels in the retinaof hemiparkinsonium rats.3,To investigate the relationship between MT1and MT2melatonin receptorsexpressions and tyrosine hydroxylase (TH) expression in the striatum, substantia nigraand retina of hemiparkinsonium rats.Methods:1,A hemiparkinsonium rat model was established by a unilateral injection of6-hydroxydopamine (6-OHDA) into the right substantia nigra pars compacta (SNc)and the right medial forebrain bundle (MFB). Dialysate samples were dynamicallycollected in the lesioned striatum of6-OHDA-induced hemiparkinsonium rats bymicrodialysis twice daily at10:00and22:00, respectively, at3w,4w,5w and6wpost-lesion. Tissue samples were collected in both ipsilateral and contralateral striata,substantia nigras and eyes to the6-OHDA-lesioned side of hemiparkinsonium rats at10:00and22:00, respectively, at3w,4w,5w and6w post-lesion. And the levels ofDA and its metabolites, such as3,4-dihydroxyphenylacetic acid (DOPAC) andhomovanillic acid (HVA), as well as MLT in dialysate samples and tissue sampleswere measured by high performance liquid chromotorgraphy (HPLC).2,The expressions of MT1and MT2melatonin receotors in both ipsilateral andcontralateral striatum, substantia nigra and eye tissues to the6-OHDA-lesioned sideof hemiparkinsonium rats were detected by RT-PCR and Western-Blot at6w post-lesion. At the same time, the expressions of MT1and MT2melatonin receotors aswell as TH were also detected by immunohistochemistry in both ipsilateral and contralateral substantia nigra and retina tissues to the lesion of hemiparkinsonium rats.Results:1,The concentrations of DA, DOPAC and HVA at10:00and22:00, respectively,in the lesioned striatum and substantia nigra of6-OHDA-induced hemiparkinsoniumrats were significantly decreased (P<0.001) and both DOPAC/DA and HVA/DAratios were increased (P<0.05) in comparison with those in the controls or in theintact striatum and substantia nigra. The levels of MLT at10:00and22:00,respectively, in the lesioned striatum and substantia nigra were distinctly increasedcompared with those in the controls or in the intact striatum and substantia nigra(P<0.05), while intact striatum and substantia nigra MLT levels showed a moderateincrease in contrast to the controls (P<0.05). The change of MLT levels appeared tocorrelate well with DA in the lesioned striatum and substantia nigra ofhemiparkinsonium rats, and the changes of DA and MLT in the lesioned striatum andsubstantia nigra also appeared to correlate well with the rotational behavior.2,The concentrations of DA, DOPAC and HVA at10:00and22:00, respectively,in the eye contralateral to the6-OHDA-lesioned side of hemiparkinsonium rats weresignificantly decreased (P<0.001) and both DOPAC/DA and HVA/DA ratios wereincreased (P<0.05) in comparison with those in the controls or in the ipsilateral eye.The levels of MLT at10:00and22:00, respectively, in the contralateral eye to thelesion were distinctly increased compared with those in the controls or in theipsilateral eye (P<0.05), while ipsilateral eye MLT levels showed a moderate increasein contrast to the controls (P<0.05). The change of MLT levels appeared to correlatewell with DA in the contralateral eye to the lesion of hemiparkinsonium rats, and thechanges of DA and MLT in the contralateral eye to the lesion appeared to correlatewell with the rotational behavior of hemiparkinsonium rats.3,The expressions of MT1and MT2melatonin receotors in the lesioned striatumand substantia nigra as well as TH in the lesioned substantia nigra of6-OHDA-induced hemiparkinsonium rats were distinctly decreased in comparison with those inthe controls or in the intact striatum and substantia nigra (P<0.01). Both MT1andMT2melatonin receptors and TH were co-localized in the substantia nigra. 4,The expressions of MT1and MT2melatonin receotors as well as TH in theretina contralateral to the lesioned side of6-OHDA-induced hemiparkinsonium ratswere significantly decreased in comparison with those in the controls or in theipsilateral retina (P<0.01). Both MT1and MT2melatonin receptors and TH wereco-localized at the border of the inner nuclear layer (INL) and the inner plexiformlayer (IPL).Conclusion:1,Significant increase of MLT levels in the lesioned striatum and substantianigra of6-OHDA-induced hemiparkinsonium rats may be associated with theprogression of Parkinson's disease (PD).2,Significant increase of MLT levels in the contralateral retina to the lesion of6-OHDA-induced hemiparkinsonium rats may be associated with the progression ofPD.3,Significant decrease of MT1and MT2melatonin receptors expression levelsin the lesioned striatum and substantia nigra as well as the contralateral retina to thelesion of6-OHDA-induced hemiparkinsonium rats may be associated with theprogression of PD. Significant increase of MLT levels in the lesioned striatum andsubstantia nigra as well as the contralateral retina to the lesion of hemiparkinsoniumrats may not exert its action by MT1and MT2melatonin receotors mediated signalpathway, while moderate increase of MLT levels in the intact striatum and substantianigra as well as the ipsilateral retina may exert such an effect. Other MLT receptorsmediated signal pathway may be associated with the progression of PD.