INTRODUCTION: In Parkinson's disease, L-dopa-induced dyskinesia (LID) and motor fluctuations incapacitate patients as much as the disease itself. Many studies demonstrated that postsynaptic alterations and striatal synaptic plasticity changes play a role in LID development. Here, we aimed to study the role of striatal presynaptic proteins in LID pathogenesis. METHODS: For this purpose, 6-hydroxydopamine model of parkinsonism was used. To induce LID, these rats were treated with intraperitoneal injections of L-dopa 25 mg/kg with benserazide 6.25 mg/kg b.i.d for 21 days. Rats with parkinsonism treated with saline and control rats treated with saline or L-dopa/ benserazide were also included. Behaviors of rats were videotaped and scored according to dyskinesia scale. Striatal tissue was analysed with immunofluorescence staining and immunoblotting to confirm loss of tyrosine hydroxylase (TH) expression due to dopaminergic denervation and to explore the alterations in the expression of presynaptic proteins, secretogranin 2 (SG2), synaptophysin (Syp) and synaptotagmin 7 (Syt7). RESULT: LID developed only in rats with parkinsonism treated with chronic L-dopa. Immunofluorescence and immunoblotting studies for TH confirmed depletion of dopaminergic neurons, which was also strongly and negatively correlated with severity of LID. Striatal SG2 and Syp levels were found increased in parkinsonian rats. Chronic L-dopa treatment further increased SG2 levels in denervated striatum. Striatal SG 2 level showed a significant moderate, positive correlation with LID severity. Immunofluorescence studies also demonstrated increased expression of these presynaptic proteins in the denervated striatum. CONCLUSION: As, severity of LID was clearly correlated with striatal SG2 expression; there is supposedly a functional relationship between striatal SG2 and LID. Further studies are needed to find out molecular mechanisms linking increased SG2 expression and LID.
INTRODUCTION: In Parkinson's disease, L-dopa-induced dyskinesia (LID) and motor fluctuations incapacitate patients as much as the disease itself. Many studies demonstrated that postsynaptic alterations and striatal synaptic plasticity changes play a role in LID development. Here, we aimed to study the role of striatal presynaptic proteins in LID pathogenesis. METHODS: For this purpose, 6-hydroxydopamine model of parkinsonism was used. To induce LID, these rats were treated with intraperitoneal injections of L-dopa 25 mg/kg with benserazide 6.25 mg/kg b.i.d for 21 days. Rats with parkinsonism treated with saline and control rats treated with saline or L-dopa/ benserazide were also included. Behaviors of rats were videotaped and scored according to dyskinesia scale. Striatal tissue was analysed with immunofluorescence staining and immunoblotting to confirm loss of tyrosine hydroxylase (TH) expression due to dopaminergic denervation and to explore the alterations in the expression of presynaptic proteins, secretogranin 2 (SG2), synaptophysin (Syp) and synaptotagmin 7 (Syt7). RESULT: LID developed only in rats with parkinsonism treated with chronic L-dopa. Immunofluorescence and immunoblotting studies for TH confirmed depletion of dopaminergic neurons, which was also strongly and negatively correlated with severity of LID. Striatal SG2 and Syp levels were found increased in parkinsonian rats. Chronic L-dopa treatment further increased SG2 levels in denervated striatum. Striatal SG 2 level showed a significant moderate, positive correlation with LID severity. Immunofluorescence studies also demonstrated increased expression of these presynaptic proteins in the denervated striatum. CONCLUSION: As, severity of LID was clearly correlated with striatal SG2 expression; there is supposedly a functional relationship between striatal SG2 and LID. Further studies are needed to find out molecular mechanisms linking increased SG2 expression and LID.
Entities:
Keywords:
Parkinson’s disease; motor fluctuations; secretogranin 2; striatum; synaptic plasticity
Authors: Z B You; A Saria; R Fischer-Colbrie; L Terenius; M Goiny; M Herrera-Marschitz Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 1996-12 Impact factor: 3.000