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P2.022 Behavioural improvements of hemiparkinsonian rats after intrastriatal injection of botulinum toxin A
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Poster presentations / Parkinsonism and Related Disorders 15S2 (2009) S29–S199
dynamin like protein-1 (Drp1) and PTEN induced putative kinase 1 (PINK1) which are involved in the mitochondrial fission and fusion machinery. The protein PINK1 was also upregulated in untreated astrocytes from THsyn and BAsyn mice compared to LM. Furthermore cells from these two lines displayed a deficit in mitochondrial Ca2+ -storage which was measured by applying FCCP – an uncoupler of the mitochondrial electron transport chain. Indirect cocultures showed differential effects of transgenic astrocytes on neuronal differentiation by secreted factors. Conclusions: These data suggest that astrocytes are prominent contributors to the pathophysiology of Parkinson’s disease.
the PD group (p < 0.0001, Mann-Whitney U test) compared with those in the control group. The area under the ROC curve (AUC) indicated sensitivity of 75.0% and specificity of 87.5% with an AUC of 0.859 for increased CSF a-syn oligomers in clinically diagnosed PD cases. However, when the ratio between CSF oligomers and total a-syn were analyzed, it provided even significant increase in sensitivity of 89.3%, and a specificity of 90.6% with an AUC of 0.948. Interpretation: Our results demonstrate that the CSF levels of a-syn oligomers and oligomers/total ratio can be a useful biomarker for diagnosis and early detection of PD, and for testing therapeutic agents aimed at preventing or reversing the aggregation of a-syn.
P2.022 Behavioural improvements of hemiparkinsonian rats after intrastriatal injection of botulinum toxin A
P2.024 Transcranial sonography in Parkinson’s disease: diagnostic and prognostic application
A. Wree1 , V. Antipova1 , A. Hawlitschka1 , R. Benecke2 , E. Mix2 . 1 Institute of Anatomy, 2 Department of Neurology, Medical Faculty/ University of Rostock, Rostock, Germany
E.Y. Fedotova1 , A.O. Chechetkin2 , N.Y. Abramycheva1 , I.A. IvanovaSmolenskaya1 , S.N. Illarioshkin1 . 1 Department of Neurogenetics, 2 Department of Ultrasonology, Research Center of Neurology, Moscow, Russia
Here we investigated consequences of intrastriatal injection of botulinum toxin A (BT-A) into rats on motor function in an animal model of Parkinson’s disease (PD) to analyze the potential applicability of the intrastriatal BT treatment as a therapeutic option of PD. Young adult Wistar rats, which had received 6-hydroxydopamine (6-OHDA) in the right medial forebrain bundle 4 weeks before BTtreatment (Hemiparkinson model) and healthy rats were injected with BT-A at (100 pg, 1 ng, 2 ng), respectively, into the right striatum. Behaviour changes were investigated by: apomorphine and amphetamine induced rotations, cylinder test according to Schallert (forepaw preference) and Rotarod test according to Dunham and Miya (forced motor activity). BT application into control rats leads to a slight dose-dependent and transient (<2 months) induction of rotations (2–3 per minute) by apomorphine clockwise. In the PD rats deafferentiation of dopaminergic neurons by 6-OHDA causes approximately 8 rotations away from the lesion (anti-clockwise). Ipsilateral injection of BT-A at doses of 1–2 ng abrogates these rotations almost completely for at least 3 months. In contrast, amphetamine induces approximately 8 rotations per minute clockwise in PD rats. Here, BT-A injections enhance the rotations, but transiently (1 month) to 12 per minute. No significant alterations in cylinder tests and Rotarod tests were seen during 3 months. In conclusion, BT-A reduces the inhibitory ipsilateral cholinergic inputs in the striatum of PD rats thereby antagoning pathological apomorphine induced rotations. We suppose that intrastriatal application of BT-A can contribute to an improved treatment of PD. P2.023 Detection of a-synuclein oligomers in CSF from Parkinson’s disease patients T. Tokuda1 , O. El-Agnaf2 . 1 Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2 Biochemistry, United Arab Emirates University, Al Ain, United Arab Emirates Background: The discovery of mutations in SNCA gene encoding a-synuclein (a-syn) in familial parkinsonism suggested a critical role for this protein in the etiology of Parkinson’s disease (PD). In addition, the neuropathologic lesions that best characterize endstage PD, Lewy bodies (LBs) are largely comprised of deposits of fibrillar a-syn. Recently, we reported the levels of total a-syn in CSF from PD patients is decreased compared to controls. Methods: Here, we investigated the levels of a-syn oligomers in CSF from 32 patients with PD and 28 age-matched controls using an enzyme-linked immunosorbent assay (ELISA) that specifically detects a-syn oligomers. We also measured the levels of CSF total a-syn using an ELISA method. Results: The levels of a-syn oligomers and the ratio between oligomers and total a-syn in CSF were significantly higher in
Background: Parkinson’s disease (PD) is characterized by a long period of latent neurodegeneration which should be the primary target of neuroprotection. The identification of individuals “at risk” may rely on well-validated biomarkers, such as: genetic testing, different neuroimaging approaches, testing for olfaction, cognitive and autonomic function, etc. Methods: In our study we used transcranial sonography as an available and harmless method characterized by rather high specificity and sensitivity in PD (hyperechogenicity of the substantia nigra). Using this method we studied several groups: idiopathic PD (N = 75 with late onset and N = 26 with early onset), asymptomatic carriers of mutations in the parkin, LRRK2 and GBA genes (N = 10), atypical and secondary parkinsonism (N = 12), essential tremor (N = 15) and control group (N = 40). Results: The lack of a sufficient acoustic window was found in 12% of examined persons. In the rest, we found that the area of hyperechogenicity in patients with PD (31.5±10.8 mm2 ) was increased compared with the other groups – atypical and secondary parkinsonism (8.4±10.9), essential tremor (9.8±10.2) and control (7.3±11.1). There was a clear difference between the early-onset (24.1±11.7) and late-onset (33.7±9.7) cases. Gene carriers were comparable with early-onset PD. Conclusions: These results show that the hyperechogenicity of the substantia nigra can be considered as a specific PD biomarker. Transcranial sonography can be applied for differential diagnosis and also for detecting predisposition to PD. Our results provided additional evidence of pathogenic heterogeneity of idiopathic PD. The study was supported by the Russian Foundation for Basic Research (grant #07-04-01682). P2.025 Amyotrophic lateral sclerosis and Hirayama disease-associated metabolite biomarker pattern revealed by 1 H NMR spectroscopy A. Kumar, J. Kalita, U.K. Misra, G.N. Babu. Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India Aims: Neurodegenerative diseases, like Amyotrophic Lateral Sclerosis (ALS) and Hirayama disease may produce characteristic perturbations of the metabolome. Methods: Serum analysis was performed by 1 H NMR. Results: Patients with ALS had significantly higher median concentrations (microM) of creatine/creatinine (43 vs 30, P < 0.02), glutamate (92 vs ND, P < 0.001), beta-hydroxybutyrate (2 vs ND, P < 0.001), acetate (15 vs 8, P < 0.01), acetone (15 vs 9, P < 0.05), and formate (16 vs ND, P < 0.001) than healthy controls, and significantly lower concentrations of N-acetyl derivatives (P < 0.001), glutamine (406 vs 448, P < 0.02) and histidine (55 vs 67, P < 0.001). On the other hand, we found that in Hirayama disease, patients had significantly
Poster presentations / Parkinsonism and Related Disorders 15S2 (2009) S29–S199
dynamin like protein-1 (Drp1) and PTEN induced putative kinase 1 (PINK1) which are involved in the mitochondrial fission and fusion machinery. The protein PINK1 was also upregulated in untreated astrocytes from THsyn and BAsyn mice compared to LM. Furthermore cells from these two lines displayed a deficit in mitochondrial Ca2+ -storage which was measured by applying FCCP – an uncoupler of the mitochondrial electron transport chain. Indirect cocultures showed differential effects of transgenic astrocytes on neuronal differentiation by secreted factors. Conclusions: These data suggest that astrocytes are prominent contributors to the pathophysiology of Parkinson’s disease.
the PD group (p < 0.0001, Mann-Whitney U test) compared with those in the control group. The area under the ROC curve (AUC) indicated sensitivity of 75.0% and specificity of 87.5% with an AUC of 0.859 for increased CSF a-syn oligomers in clinically diagnosed PD cases. However, when the ratio between CSF oligomers and total a-syn were analyzed, it provided even significant increase in sensitivity of 89.3%, and a specificity of 90.6% with an AUC of 0.948. Interpretation: Our results demonstrate that the CSF levels of a-syn oligomers and oligomers/total ratio can be a useful biomarker for diagnosis and early detection of PD, and for testing therapeutic agents aimed at preventing or reversing the aggregation of a-syn.
P2.022 Behavioural improvements of hemiparkinsonian rats after intrastriatal injection of botulinum toxin A
P2.024 Transcranial sonography in Parkinson’s disease: diagnostic and prognostic application
A. Wree1 , V. Antipova1 , A. Hawlitschka1 , R. Benecke2 , E. Mix2 . 1 Institute of Anatomy, 2 Department of Neurology, Medical Faculty/ University of Rostock, Rostock, Germany
E.Y. Fedotova1 , A.O. Chechetkin2 , N.Y. Abramycheva1 , I.A. IvanovaSmolenskaya1 , S.N. Illarioshkin1 . 1 Department of Neurogenetics, 2 Department of Ultrasonology, Research Center of Neurology, Moscow, Russia
Here we investigated consequences of intrastriatal injection of botulinum toxin A (BT-A) into rats on motor function in an animal model of Parkinson’s disease (PD) to analyze the potential applicability of the intrastriatal BT treatment as a therapeutic option of PD. Young adult Wistar rats, which had received 6-hydroxydopamine (6-OHDA) in the right medial forebrain bundle 4 weeks before BTtreatment (Hemiparkinson model) and healthy rats were injected with BT-A at (100 pg, 1 ng, 2 ng), respectively, into the right striatum. Behaviour changes were investigated by: apomorphine and amphetamine induced rotations, cylinder test according to Schallert (forepaw preference) and Rotarod test according to Dunham and Miya (forced motor activity). BT application into control rats leads to a slight dose-dependent and transient (<2 months) induction of rotations (2–3 per minute) by apomorphine clockwise. In the PD rats deafferentiation of dopaminergic neurons by 6-OHDA causes approximately 8 rotations away from the lesion (anti-clockwise). Ipsilateral injection of BT-A at doses of 1–2 ng abrogates these rotations almost completely for at least 3 months. In contrast, amphetamine induces approximately 8 rotations per minute clockwise in PD rats. Here, BT-A injections enhance the rotations, but transiently (1 month) to 12 per minute. No significant alterations in cylinder tests and Rotarod tests were seen during 3 months. In conclusion, BT-A reduces the inhibitory ipsilateral cholinergic inputs in the striatum of PD rats thereby antagoning pathological apomorphine induced rotations. We suppose that intrastriatal application of BT-A can contribute to an improved treatment of PD. P2.023 Detection of a-synuclein oligomers in CSF from Parkinson’s disease patients T. Tokuda1 , O. El-Agnaf2 . 1 Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2 Biochemistry, United Arab Emirates University, Al Ain, United Arab Emirates Background: The discovery of mutations in SNCA gene encoding a-synuclein (a-syn) in familial parkinsonism suggested a critical role for this protein in the etiology of Parkinson’s disease (PD). In addition, the neuropathologic lesions that best characterize endstage PD, Lewy bodies (LBs) are largely comprised of deposits of fibrillar a-syn. Recently, we reported the levels of total a-syn in CSF from PD patients is decreased compared to controls. Methods: Here, we investigated the levels of a-syn oligomers in CSF from 32 patients with PD and 28 age-matched controls using an enzyme-linked immunosorbent assay (ELISA) that specifically detects a-syn oligomers. We also measured the levels of CSF total a-syn using an ELISA method. Results: The levels of a-syn oligomers and the ratio between oligomers and total a-syn in CSF were significantly higher in
Background: Parkinson’s disease (PD) is characterized by a long period of latent neurodegeneration which should be the primary target of neuroprotection. The identification of individuals “at risk” may rely on well-validated biomarkers, such as: genetic testing, different neuroimaging approaches, testing for olfaction, cognitive and autonomic function, etc. Methods: In our study we used transcranial sonography as an available and harmless method characterized by rather high specificity and sensitivity in PD (hyperechogenicity of the substantia nigra). Using this method we studied several groups: idiopathic PD (N = 75 with late onset and N = 26 with early onset), asymptomatic carriers of mutations in the parkin, LRRK2 and GBA genes (N = 10), atypical and secondary parkinsonism (N = 12), essential tremor (N = 15) and control group (N = 40). Results: The lack of a sufficient acoustic window was found in 12% of examined persons. In the rest, we found that the area of hyperechogenicity in patients with PD (31.5±10.8 mm2 ) was increased compared with the other groups – atypical and secondary parkinsonism (8.4±10.9), essential tremor (9.8±10.2) and control (7.3±11.1). There was a clear difference between the early-onset (24.1±11.7) and late-onset (33.7±9.7) cases. Gene carriers were comparable with early-onset PD. Conclusions: These results show that the hyperechogenicity of the substantia nigra can be considered as a specific PD biomarker. Transcranial sonography can be applied for differential diagnosis and also for detecting predisposition to PD. Our results provided additional evidence of pathogenic heterogeneity of idiopathic PD. The study was supported by the Russian Foundation for Basic Research (grant #07-04-01682). P2.025 Amyotrophic lateral sclerosis and Hirayama disease-associated metabolite biomarker pattern revealed by 1 H NMR spectroscopy A. Kumar, J. Kalita, U.K. Misra, G.N. Babu. Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India Aims: Neurodegenerative diseases, like Amyotrophic Lateral Sclerosis (ALS) and Hirayama disease may produce characteristic perturbations of the metabolome. Methods: Serum analysis was performed by 1 H NMR. Results: Patients with ALS had significantly higher median concentrations (microM) of creatine/creatinine (43 vs 30, P < 0.02), glutamate (92 vs ND, P < 0.001), beta-hydroxybutyrate (2 vs ND, P < 0.001), acetate (15 vs 8, P < 0.01), acetone (15 vs 9, P < 0.05), and formate (16 vs ND, P < 0.001) than healthy controls, and significantly lower concentrations of N-acetyl derivatives (P < 0.001), glutamine (406 vs 448, P < 0.02) and histidine (55 vs 67, P < 0.001). On the other hand, we found that in Hirayama disease, patients had significantly