Glutamate and NMDA receptors activation leads to cerebellar dysfunction and impaired motor coordination in unilateral 6-hydroxydopamine lesioned Parkinson’s rat: functional recovery with bone marrow cells, serotonin and GABA
Parkinson’s disease (PD) is a chronic progressive neurodegenerative movement disorder characterised by a profound and selective loss of nigrostriatal dopaminergic neurons. In Parkinson’s disease, degeneration of dopaminergic neurons involves motor structures including basal ganglia and cerebellum. G...
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| Veröffentlicht in: | Molecular and cellular biochemistry 2011-07, Vol.353 (1-2), p.47-57 |
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| creator | Nandhu, M. S. Paul, Jes Kuruvila, Korah P. Abraham, Pretty M. Antony, Sherin Paulose, C. S. |
| description | Parkinson’s disease (PD) is a chronic progressive neurodegenerative movement disorder characterised by a profound and selective loss of nigrostriatal dopaminergic neurons. In Parkinson’s disease, degeneration of dopaminergic neurons involves motor structures including basal ganglia and cerebellum. Glutamate-mediated degeneration of the cerebellum contributes to motor dysfunction in Parkinson’s disease. Targeting neurotransmitter system beyond the dopamine system is of important, both for the motor and for the nonmotor problems of Parkinson’s disease. The aim of this study is to assess the glutamate and NMDA receptor functional regulation and motor performance of 6-hydroxydopamine-induced Parkinson’s rat and the effects of serotonin (5-HT), gamma aminobutyric acid (GABA) and bone marrow cells supplementation infused intranigrally to substantia nigra individually and in combination. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed a significant increase in
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max
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| doi_str_mv | 10.1007/s11010-011-0773-x |
| format | Article |
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B
max
(
P
< 0.001) in the cerebellum of 6-hydroxydopamine infused rat compared to control. Real-Time PCR amplification of NMDA2B, mGluR5, and bax were significantly (
P
< 0.001) upregulated in cerebellum of 6-hydroxydopamine infused rats compared to control. Activation of the glutamate and NMDA receptors gave rise to an increased cAMP and IP3 content in the cerebellum. Gene expression studies of GLAST and CREB showed a significant (
P
< 0.001) down regulation in 6-OHDA infused rats compared to control. Behavioural studies were carried out to confirm the biochemical and molecular studies. Serotonin and GABA along with bone marrow cells in combination showed reversal of glutamate receptors and motor abnormality shown in the Parkinson’s rat model. The therapeutic significance in Parkinson’s disease is of prominence.</description><identifier>ISSN: 0300-8177</identifier><identifier>EISSN: 1573-4919</identifier><identifier>DOI: 10.1007/s11010-011-0773-x</identifier><identifier>PMID: 21384157</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Animals ; bcl-2-Associated X Protein - genetics ; bcl-2-Associated X Protein - metabolism ; Binding, Competitive ; Biochemistry ; Biomedical and Life Sciences ; Bone marrow ; Brain ; Cardiology ; Cerebellar Diseases - chemically induced ; Cerebellar Diseases - physiopathology ; Cerebellar Diseases - therapy ; Cerebellum - metabolism ; Cerebellum - physiopathology ; Cyclic AMP - metabolism ; Dizocilpine Maleate - metabolism ; GABA ; Glutamate ; Inositol Phosphates - metabolism ; Life Sciences ; Male ; Medical Biochemistry ; Methyl aspartate ; Microscopy, Confocal ; Motor Activity - physiology ; Neurons ; Oncology ; Oxidopamine ; Parkinson Disease, Secondary - chemically induced ; Parkinson Disease, Secondary - physiopathology ; Parkinson Disease, Secondary - therapy ; Parkinson's disease ; Phenols ; Rats ; Rats, Wistar ; Receptor, Metabotropic Glutamate 5 ; Receptors, Glutamate - genetics ; Receptors, Glutamate - metabolism ; Receptors, Metabotropic Glutamate - genetics ; Receptors, Metabotropic Glutamate - metabolism ; Receptors, N-Methyl-D-Aspartate - genetics ; Receptors, N-Methyl-D-Aspartate - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Rodents ; Serotonin</subject><ispartof>Molecular and cellular biochemistry, 2011-07, Vol.353 (1-2), p.47-57</ispartof><rights>Springer Science+Business Media, LLC. 2011</rights><rights>COPYRIGHT 2011 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-1ee62518195218f9c5de6adf8c459784412bdcdb98a16442678ec0b2997c73df3</citedby><cites>FETCH-LOGICAL-c442t-1ee62518195218f9c5de6adf8c459784412bdcdb98a16442678ec0b2997c73df3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11010-011-0773-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11010-011-0773-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21384157$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nandhu, M. S.</creatorcontrib><creatorcontrib>Paul, Jes</creatorcontrib><creatorcontrib>Kuruvila, Korah P.</creatorcontrib><creatorcontrib>Abraham, Pretty M.</creatorcontrib><creatorcontrib>Antony, Sherin</creatorcontrib><creatorcontrib>Paulose, C. S.</creatorcontrib><title>Glutamate and NMDA receptors activation leads to cerebellar dysfunction and impaired motor coordination in unilateral 6-hydroxydopamine lesioned Parkinson’s rat: functional recovery with bone marrow cells, serotonin and GABA</title><title>Molecular and cellular biochemistry</title><addtitle>Mol Cell Biochem</addtitle><addtitle>Mol Cell Biochem</addtitle><description>Parkinson’s disease (PD) is a chronic progressive neurodegenerative movement disorder characterised by a profound and selective loss of nigrostriatal dopaminergic neurons. In Parkinson’s disease, degeneration of dopaminergic neurons involves motor structures including basal ganglia and cerebellum. Glutamate-mediated degeneration of the cerebellum contributes to motor dysfunction in Parkinson’s disease. Targeting neurotransmitter system beyond the dopamine system is of important, both for the motor and for the nonmotor problems of Parkinson’s disease. The aim of this study is to assess the glutamate and NMDA receptor functional regulation and motor performance of 6-hydroxydopamine-induced Parkinson’s rat and the effects of serotonin (5-HT), gamma aminobutyric acid (GABA) and bone marrow cells supplementation infused intranigrally to substantia nigra individually and in combination. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed a significant increase in
B
max
(
P
< 0.001) in the cerebellum of 6-hydroxydopamine infused rat compared to control. Real-Time PCR amplification of NMDA2B, mGluR5, and bax were significantly (
P
< 0.001) upregulated in cerebellum of 6-hydroxydopamine infused rats compared to control. Activation of the glutamate and NMDA receptors gave rise to an increased cAMP and IP3 content in the cerebellum. Gene expression studies of GLAST and CREB showed a significant (
P
< 0.001) down regulation in 6-OHDA infused rats compared to control. Behavioural studies were carried out to confirm the biochemical and molecular studies. Serotonin and GABA along with bone marrow cells in combination showed reversal of glutamate receptors and motor abnormality shown in the Parkinson’s rat model. The therapeutic significance in Parkinson’s disease is of prominence.</description><subject>Animals</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Binding, Competitive</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Bone marrow</subject><subject>Brain</subject><subject>Cardiology</subject><subject>Cerebellar Diseases - chemically induced</subject><subject>Cerebellar Diseases - physiopathology</subject><subject>Cerebellar Diseases - therapy</subject><subject>Cerebellum - metabolism</subject><subject>Cerebellum - physiopathology</subject><subject>Cyclic AMP - metabolism</subject><subject>Dizocilpine Maleate - metabolism</subject><subject>GABA</subject><subject>Glutamate</subject><subject>Inositol Phosphates - metabolism</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Medical Biochemistry</subject><subject>Methyl aspartate</subject><subject>Microscopy, Confocal</subject><subject>Motor Activity - physiology</subject><subject>Neurons</subject><subject>Oncology</subject><subject>Oxidopamine</subject><subject>Parkinson Disease, Secondary - chemically induced</subject><subject>Parkinson Disease, Secondary - physiopathology</subject><subject>Parkinson Disease, Secondary - therapy</subject><subject>Parkinson's disease</subject><subject>Phenols</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptor, Metabotropic Glutamate 5</subject><subject>Receptors, Glutamate - genetics</subject><subject>Receptors, Glutamate - metabolism</subject><subject>Receptors, Metabotropic Glutamate - genetics</subject><subject>Receptors, Metabotropic Glutamate - metabolism</subject><subject>Receptors, N-Methyl-D-Aspartate - genetics</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Rodents</subject><subject>Serotonin</subject><issn>0300-8177</issn><issn>1573-4919</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1ks1u1DAUhSMEokPhAdggixULUuz8OuxCKQNS-VnAOnLsm9YlsYdrp53Z9TV4vT4Jd0gLEhLKIlF8vnOP7ZMkTwU_EpzXr4IQXPCUC5Hyus7T7b1kJUr6KBrR3E9WPOc8laKuD5JHIVxwEpP2YXKQiVwWpFwlN-txjmpSEZhyhn36-LZlCBo20WNgSkd7qaL1jo2gTGDRMw0IPYyjQmZ2YZid_r2-p-20URbBsMkTzrT3aKxbeOvY7OxIg1CNrErPdwb9dmf8Rk3WAfkHkhH7ReF364J3N9c_A0MVX7O7IQRSNn8JuGNXNp6zngg2KUR_RbnGMbxkAZCGO7skWrdv2sfJg0GNAZ7cvg-Tb-9Ovh6_T08_rz8ct6epLoospgKgykohRVNmQg6NLg1UygxSF2VTy6IQWW-06RupREVEVUvQvM-aptZ1bob8MHmx-G7Q_5ghxG6yYZ9KOfBz6ATPJCcjUZP0-T_SCz8j7S90smoKup2yINHRIjpTI3TWDT6i0vQYmKymnQ-W_rd52XBZVHLvKhZAow8BYeg2aOl0djS62xemWwrTUQm6fWG6LTHPbpPM_QTmD3HXEBJkiyDQkjsD_Bv1_66_AKjX0aI</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>Nandhu, M. 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S.</au><au>Paul, Jes</au><au>Kuruvila, Korah P.</au><au>Abraham, Pretty M.</au><au>Antony, Sherin</au><au>Paulose, C. S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glutamate and NMDA receptors activation leads to cerebellar dysfunction and impaired motor coordination in unilateral 6-hydroxydopamine lesioned Parkinson’s rat: functional recovery with bone marrow cells, serotonin and GABA</atitle><jtitle>Molecular and cellular biochemistry</jtitle><stitle>Mol Cell Biochem</stitle><addtitle>Mol Cell Biochem</addtitle><date>2011-07-01</date><risdate>2011</risdate><volume>353</volume><issue>1-2</issue><spage>47</spage><epage>57</epage><pages>47-57</pages><issn>0300-8177</issn><eissn>1573-4919</eissn><abstract>Parkinson’s disease (PD) is a chronic progressive neurodegenerative movement disorder characterised by a profound and selective loss of nigrostriatal dopaminergic neurons. In Parkinson’s disease, degeneration of dopaminergic neurons involves motor structures including basal ganglia and cerebellum. Glutamate-mediated degeneration of the cerebellum contributes to motor dysfunction in Parkinson’s disease. Targeting neurotransmitter system beyond the dopamine system is of important, both for the motor and for the nonmotor problems of Parkinson’s disease. The aim of this study is to assess the glutamate and NMDA receptor functional regulation and motor performance of 6-hydroxydopamine-induced Parkinson’s rat and the effects of serotonin (5-HT), gamma aminobutyric acid (GABA) and bone marrow cells supplementation infused intranigrally to substantia nigra individually and in combination. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed a significant increase in
B
max
(
P
< 0.001) in the cerebellum of 6-hydroxydopamine infused rat compared to control. Real-Time PCR amplification of NMDA2B, mGluR5, and bax were significantly (
P
< 0.001) upregulated in cerebellum of 6-hydroxydopamine infused rats compared to control. Activation of the glutamate and NMDA receptors gave rise to an increased cAMP and IP3 content in the cerebellum. Gene expression studies of GLAST and CREB showed a significant (
P
< 0.001) down regulation in 6-OHDA infused rats compared to control. Behavioural studies were carried out to confirm the biochemical and molecular studies. Serotonin and GABA along with bone marrow cells in combination showed reversal of glutamate receptors and motor abnormality shown in the Parkinson’s rat model. The therapeutic significance in Parkinson’s disease is of prominence.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>21384157</pmid><doi>10.1007/s11010-011-0773-x</doi><tpages>11</tpages></addata></record> |
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| subjects | Animals bcl-2-Associated X Protein - genetics bcl-2-Associated X Protein - metabolism Binding, Competitive Biochemistry Biomedical and Life Sciences Bone marrow Brain Cardiology Cerebellar Diseases - chemically induced Cerebellar Diseases - physiopathology Cerebellar Diseases - therapy Cerebellum - metabolism Cerebellum - physiopathology Cyclic AMP - metabolism Dizocilpine Maleate - metabolism GABA Glutamate Inositol Phosphates - metabolism Life Sciences Male Medical Biochemistry Methyl aspartate Microscopy, Confocal Motor Activity - physiology Neurons Oncology Oxidopamine Parkinson Disease, Secondary - chemically induced Parkinson Disease, Secondary - physiopathology Parkinson Disease, Secondary - therapy Parkinson's disease Phenols Rats Rats, Wistar Receptor, Metabotropic Glutamate 5 Receptors, Glutamate - genetics Receptors, Glutamate - metabolism Receptors, Metabotropic Glutamate - genetics Receptors, Metabotropic Glutamate - metabolism Receptors, N-Methyl-D-Aspartate - genetics Receptors, N-Methyl-D-Aspartate - metabolism Reverse Transcriptase Polymerase Chain Reaction Rodents Serotonin |
| title | Glutamate and NMDA receptors activation leads to cerebellar dysfunction and impaired motor coordination in unilateral 6-hydroxydopamine lesioned Parkinson’s rat: functional recovery with bone marrow cells, serotonin and GABA |
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