Resumo

OBJECTIVES: Dopamine (DA) receptors play an important role in movement, reward, and learning and are implicated in a number of neurological and psychiatric disorders. These receptors are concentrated in dendritic spines of neurons. PSD-95 is a prototypical scaffolding protein highly enriched in the PSD (postsynaptic density) and belongs to the membrane-associated guanylate kinase family. PSD may play an important role in functional regulation of the DA receptor because physically associates with either D1 or D2 DA receptors and regulates its trafficking and function. Abnormal PSD-95 expression has been implicated in Parkinson’s disease (PD). Therefore, the aim of this study was to evaluate the time course of PSD-95 content modulation in the striatum using a mice model of PD. METHODS: Adult C57⁄BL10 mice were anesthetized and submitted to unilateral injection of 6-OHDA prepared freshly (2µl at a rate of 0,5µl/5 min) into the right medial forebrain bundle using stereotaxic procedures. Using a video camera to recording (Sony DSC-W1) and a box, rotation test was performed after intraperitoneal injection of apomorphine (0,5mg/kg) 1, 2 and 4 weeks after surgery to evaluate the locomotor activity. Then, the brain was removed and striatum was extracted to perform western blot (WB) analysis. The expression of tyrosine hydroxilase (TH) and PSD-95 were evaluated with specific antibodies. RESULTS: Lesioned mice presented remarkable difficulties in coordinating movements in every time analyzed. A contra-lateral rotational activity was also observed, especially after 2 weeks survival. The WB analysis demonstrates a transient increase in TH expression after 2 weeks post- lesion followed by decrease below to control levels after 4 weeks. At this time,PSD-95 content is enhanced in the lesioned striatum. CONCLUSION:. Our data suggest an attempt to restore dopamine levels 2 weeks after lesion. followed by a possible change in dopaminergic receptors modulation within the period analyzed. This may be useful to develop a time-window for new therapeutic strategies. Key words: 6-OHDA,striatum, PSD-95,TH,Parkinson´s disease