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
| Autor: | Jes Paul, C.S. Paulose, Pretty Mary Abraham, Korah P. Kuruvila, Sherin Antony, M. S. Nandhu |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Cerebellum Parkinson's disease Inositol Phosphates Receptor Metabotropic Glutamate 5 Clinical Biochemistry Substantia nigra Biology Motor Activity Receptors Metabotropic Glutamate Binding Competitive Receptors N-Methyl-D-Aspartate chemistry.chemical_compound Dopamine Cerebellar Diseases Internal medicine medicine Cyclic AMP Animals Parkinson Disease Secondary Rats Wistar Oxidopamine Molecular Biology bcl-2-Associated X Protein Microscopy Confocal Metabotropic glutamate receptor 5 Reverse Transcriptase Polymerase Chain Reaction Glutamate receptor Cell Biology General Medicine medicine.disease Rats medicine.anatomical_structure Endocrinology nervous system chemistry Receptors Glutamate NMDA receptor Dizocilpine Maleate medicine.drug |
| Zdroj: | Molecular and cellular biochemistry. 353(1-2) |
| ISSN: | 1573-4919 |
| Popis: | 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 Bmax (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. |
| Databáze: | OpenAIRE |
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