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Increased density of large calretinin expressing interneurons in the striatum of Parkinsonian monkeys
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Abstracts / Parkinsonism and Related Disorders 22 (2016) e149ee192
injected MPTP and then ACEA, 7 days after injection of MPTP to assess preservation of dopamine function in brain. In the third group after 2 days of pretreatment with ACEA (intraperitoneal), MPTP were injected to assay neuroprotection effect of ACEA. Results: Behavioural analysis showed significant improvement in ACEA pretreatment group. Also Neurochemical analysis that were used to assess dopamine metabolites and immunohistochemistry studies after, brain resection showed significant rise in dopamine metabolites , CB1 receptors upregulation and survival of dopaminergic neurons in compared with controls. Conclusions: Our data indicates that ACEA as a CB1 receptor agonist protects against MPTP-induced nigrostriatal degeneration by inhibiting microglial cells activation that suggests ACEA as a new therapeutic target to slow down the degenerative process occurring and to improve motor function in PD. Ă
P 6.030. INCREASED DENSITY OF LARGE CALRETININ EXPRESSING INTERNEURONS IN THE STRIATUM OF PARKINSONIAN MONKEYS Sarah Petryszyn, Martin Parent. Centre de Recherche de l'Institut Universitaire en Sant e Mentale de Qu ebec, Qu ebec, Canada Objectives: Interneurons of the striatum play a crucial role in its functional organization. This study provides the first detailed morphological description of the distribution and chemical phenotype of calretinin (CR) interneurons of the striatum in a primate model of Parkinson's disease. Methods: Equally-spaced transverse sections taken throughout the entire striatum of four MPTP monkeys and four controls were stained for CR and NADPH. Density of CR immunostained neurons was quantified using an unbiased stereological approach. Results: In control animals, the density of CR interneurons was twice as high in the associative caudate nucleus (1,747 ± 163 neurons / mm3) than in the sensorimotor putamen (834 ± 28 neurons / mm3). Examination of immunostained sections from MPTP and control monkeys revealed three distinct groups of CR interneurons based on their soma size. In MPTP monkeys, we observed a 9-fold increase in the density of the large (20-35 mm) CR interneurons in the caudate nucleus and a 4-fold increase in the putamen, with only minimal changes in regards to the small (5-10 mm) and medium (10-20 mm) CR interneurons. Double immunostaining for NADPH and CR revealed the presence of a few double-labeled neurons in both, controls and MPTP monkeys. Conclusions: Our data indicate that lesion of the dopamine striatal input leads to an increase in the density of the large CR interneurons in both, the caudate nucleus and the putamen. P 6.031. EFFECTS OF ARACHIDONYL-2′-CHLOROETHYLAMIDE (ACEA) AS A CB1 RECEPTOR AGONIST IN THE RAT MODEL OF PARKINSON'S DISEASE Mahmoud Omidbeigi 1, Sina Asaadi 2, Zohreh Gholizadeh 2, Hossein Pakdaman 3. 1 Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran; 2 Functional Neurosurgery Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran; 3 Department of Neurology, Logman-e-hakim Hospital, Tehran, Islamic Republic of Iran Objectives: Cannabinoids have been demonstrated to be effective in preclinical studies involving oxidative stress, neuroinflammation, and motor complications associated with Parkinson's Disease (PD).The CB1 cannabinoid receptors are abundantly expressed in the basal ganglia, the circuitry that is mostly affected in PD. In this study we investigated effect of Arachidonyl-20 -chloroethylamide ( ACEA) as a CB1 receptor agonist in 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD model in male rats to assess the neuroprotective role of ACEA in slowing down of PD progression and improvement of motor function. Methods: Ninety rats were divided to three groups. One group were injected MPTP(systemically) as a control group. Second group were
P 6.032. PHOSPHORYLATION BY OKADAIC ACID ENHANCES MPP+ INDUCED HYDROXYL RADICAL GENERATION IN RAT STRIATUM Toshio Obata 1, Michiko Nakajima 2. 1 Osaka Aoyama University, Osaka, Japan; 2 Department of Nursing, School of Health Sciences, Asahi University, Gifu, Japan Objectives: The present study examined the effect of okadaic acid, an inhibitor of protein phosphatase, on 1-methyl-4-phenylpyridinium ion (MPP+)-induced hydroxyl radical (OH) generation via dopamine (DA) release in rat striatum. Methods: Rats were anesthetized, and sodium salicylate (0.5 mM or 0.5 nmol/microl/min) was infused through a microdialysis probe to detect the OH generation as reflected by the non-enzymatic formation of 2,3dihydroxybenzoic acid (2,3-DHBA) in the striatum. Results: Okadaic acid (10 mM), an inhibitor of protein phosphatase, enhanced generation of OH by MPP+ with concomitant increased efflux of DA. The application of tamoxifen (100 mmol/L), a protein kinase C (PKC) inhibitor, significantly attenuated okadaic acid enhanced MPP+-induced OH formation via DA release. Conclusions: These results suggest that activation of PKC via phosphorylation enhances MPP+-induced OH generation via DA release in rat brain. P 6.033. STUDYING PAIN-RELATED MANIFESTATIONS IN AN MPTP-INDUCED RAT MODEL OF PARKINSON'S DISEASE Manuela Padurariu 1, Alin Ciobica 2, Radu Lefter 3, Emil Anton 1. 1 Gr. T. Popa University, Iasi, Romania; 2 Alexandru Ioan Cuza University, Iasi, Romania; 3 Romanian Academy, Iasi, Romania Objectives: Parkinson's disease (PD) is less widely appreciated as a disease causing pain syndromes, although pain is found in 40-80 % of PD patients, as described by the very few reports in this area of research. Moreover, in some PD patients, pain is so severe and intractable that it overshadows the motor symptoms of the disorder. Still, pain in PD frequently goes underacknowledged and undertreated. Also, the studies regarding pain perception in the existing animal models of PD are very few. Methods: We experimentally induced the PD model in rats by injecting subcutaneously one dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 20mg/kg, while the control group received saline. The behavioral testing for pain included the hot-plate task and was performed 7 days after MPTP injection. Results: Our rat model resulted from the acute treatment with a low dose of MPTP, exhibited an increased sensitivity to pain perception, as demonstrated by the significant decrease in the values of the latency time in hot-plate for rats treated with MPTP, as compared to the controls. The latency time is expressed in seconds and is referring to the reaction time to two different types of behavior: licking the paw and jumping (11.33 s ± 2.1 in controls vs. 6.8 s ± 4.1 in MPTP group). Conclusions: Our data is suggesting, for the first time in our best of knowledge, an increased sensitivity to pain in a MPTP-induced rat model of PD. In this way, further studies in this area of research seem warranted.
Abstracts / Parkinsonism and Related Disorders 22 (2016) e149ee192
injected MPTP and then ACEA, 7 days after injection of MPTP to assess preservation of dopamine function in brain. In the third group after 2 days of pretreatment with ACEA (intraperitoneal), MPTP were injected to assay neuroprotection effect of ACEA. Results: Behavioural analysis showed significant improvement in ACEA pretreatment group. Also Neurochemical analysis that were used to assess dopamine metabolites and immunohistochemistry studies after, brain resection showed significant rise in dopamine metabolites , CB1 receptors upregulation and survival of dopaminergic neurons in compared with controls. Conclusions: Our data indicates that ACEA as a CB1 receptor agonist protects against MPTP-induced nigrostriatal degeneration by inhibiting microglial cells activation that suggests ACEA as a new therapeutic target to slow down the degenerative process occurring and to improve motor function in PD. Ă
P 6.030. INCREASED DENSITY OF LARGE CALRETININ EXPRESSING INTERNEURONS IN THE STRIATUM OF PARKINSONIAN MONKEYS Sarah Petryszyn, Martin Parent. Centre de Recherche de l'Institut Universitaire en Sant e Mentale de Qu ebec, Qu ebec, Canada Objectives: Interneurons of the striatum play a crucial role in its functional organization. This study provides the first detailed morphological description of the distribution and chemical phenotype of calretinin (CR) interneurons of the striatum in a primate model of Parkinson's disease. Methods: Equally-spaced transverse sections taken throughout the entire striatum of four MPTP monkeys and four controls were stained for CR and NADPH. Density of CR immunostained neurons was quantified using an unbiased stereological approach. Results: In control animals, the density of CR interneurons was twice as high in the associative caudate nucleus (1,747 ± 163 neurons / mm3) than in the sensorimotor putamen (834 ± 28 neurons / mm3). Examination of immunostained sections from MPTP and control monkeys revealed three distinct groups of CR interneurons based on their soma size. In MPTP monkeys, we observed a 9-fold increase in the density of the large (20-35 mm) CR interneurons in the caudate nucleus and a 4-fold increase in the putamen, with only minimal changes in regards to the small (5-10 mm) and medium (10-20 mm) CR interneurons. Double immunostaining for NADPH and CR revealed the presence of a few double-labeled neurons in both, controls and MPTP monkeys. Conclusions: Our data indicate that lesion of the dopamine striatal input leads to an increase in the density of the large CR interneurons in both, the caudate nucleus and the putamen. P 6.031. EFFECTS OF ARACHIDONYL-2′-CHLOROETHYLAMIDE (ACEA) AS A CB1 RECEPTOR AGONIST IN THE RAT MODEL OF PARKINSON'S DISEASE Mahmoud Omidbeigi 1, Sina Asaadi 2, Zohreh Gholizadeh 2, Hossein Pakdaman 3. 1 Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran; 2 Functional Neurosurgery Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran; 3 Department of Neurology, Logman-e-hakim Hospital, Tehran, Islamic Republic of Iran Objectives: Cannabinoids have been demonstrated to be effective in preclinical studies involving oxidative stress, neuroinflammation, and motor complications associated with Parkinson's Disease (PD).The CB1 cannabinoid receptors are abundantly expressed in the basal ganglia, the circuitry that is mostly affected in PD. In this study we investigated effect of Arachidonyl-20 -chloroethylamide ( ACEA) as a CB1 receptor agonist in 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD model in male rats to assess the neuroprotective role of ACEA in slowing down of PD progression and improvement of motor function. Methods: Ninety rats were divided to three groups. One group were injected MPTP(systemically) as a control group. Second group were
P 6.032. PHOSPHORYLATION BY OKADAIC ACID ENHANCES MPP+ INDUCED HYDROXYL RADICAL GENERATION IN RAT STRIATUM Toshio Obata 1, Michiko Nakajima 2. 1 Osaka Aoyama University, Osaka, Japan; 2 Department of Nursing, School of Health Sciences, Asahi University, Gifu, Japan Objectives: The present study examined the effect of okadaic acid, an inhibitor of protein phosphatase, on 1-methyl-4-phenylpyridinium ion (MPP+)-induced hydroxyl radical (OH) generation via dopamine (DA) release in rat striatum. Methods: Rats were anesthetized, and sodium salicylate (0.5 mM or 0.5 nmol/microl/min) was infused through a microdialysis probe to detect the OH generation as reflected by the non-enzymatic formation of 2,3dihydroxybenzoic acid (2,3-DHBA) in the striatum. Results: Okadaic acid (10 mM), an inhibitor of protein phosphatase, enhanced generation of OH by MPP+ with concomitant increased efflux of DA. The application of tamoxifen (100 mmol/L), a protein kinase C (PKC) inhibitor, significantly attenuated okadaic acid enhanced MPP+-induced OH formation via DA release. Conclusions: These results suggest that activation of PKC via phosphorylation enhances MPP+-induced OH generation via DA release in rat brain. P 6.033. STUDYING PAIN-RELATED MANIFESTATIONS IN AN MPTP-INDUCED RAT MODEL OF PARKINSON'S DISEASE Manuela Padurariu 1, Alin Ciobica 2, Radu Lefter 3, Emil Anton 1. 1 Gr. T. Popa University, Iasi, Romania; 2 Alexandru Ioan Cuza University, Iasi, Romania; 3 Romanian Academy, Iasi, Romania Objectives: Parkinson's disease (PD) is less widely appreciated as a disease causing pain syndromes, although pain is found in 40-80 % of PD patients, as described by the very few reports in this area of research. Moreover, in some PD patients, pain is so severe and intractable that it overshadows the motor symptoms of the disorder. Still, pain in PD frequently goes underacknowledged and undertreated. Also, the studies regarding pain perception in the existing animal models of PD are very few. Methods: We experimentally induced the PD model in rats by injecting subcutaneously one dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 20mg/kg, while the control group received saline. The behavioral testing for pain included the hot-plate task and was performed 7 days after MPTP injection. Results: Our rat model resulted from the acute treatment with a low dose of MPTP, exhibited an increased sensitivity to pain perception, as demonstrated by the significant decrease in the values of the latency time in hot-plate for rats treated with MPTP, as compared to the controls. The latency time is expressed in seconds and is referring to the reaction time to two different types of behavior: licking the paw and jumping (11.33 s ± 2.1 in controls vs. 6.8 s ± 4.1 in MPTP group). Conclusions: Our data is suggesting, for the first time in our best of knowledge, an increased sensitivity to pain in a MPTP-induced rat model of PD. In this way, further studies in this area of research seem warranted.