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.

Publisher: Springer Country of Publication: Netherlands NLM ID: 0364456 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-4919 (Electronic) Linking ISSN: 03008177 NLM ISO Abbreviation: Mol Cell Biochem Subsets: MEDLINE

Publication: New York : Springer
Original Publication: The Hague, Dr. W. Junk B. V. Publishers.

Cerebellar Diseases/*physiopathology ; Motor Activity/*physiology ; Parkinson Disease, Secondary/*physiopathology ; Receptors, Glutamate/*metabolism ; Receptors, N-Methyl-D-Aspartate/*metabolism; Animals ; Binding, Competitive ; Cerebellar Diseases/chemically induced ; Cerebellar Diseases/therapy ; Cerebellum/metabolism ; Cerebellum/physiopathology ; Cyclic AMP/metabolism ; Dizocilpine Maleate/metabolism ; Inositol Phosphates/metabolism ; Male ; Microscopy, Confocal ; Oxidopamine ; Parkinson Disease, Secondary/chemically induced ; Parkinson Disease, Secondary/therapy ; Rats ; Rats, Wistar ; Receptor, Metabotropic Glutamate 5 ; Receptors, Glutamate/genetics ; Receptors, Metabotropic Glutamate/genetics ; Receptors, Metabotropic Glutamate/metabolism ; Receptors, N-Methyl-D-Aspartate/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; bcl-2-Associated X Protein/genetics ; bcl-2-Associated X Protein/metabolism

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.

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0 (Grm5 protein, rat)
0 (Inositol Phosphates)
0 (NR2B NMDA receptor)
0 (Receptor, Metabotropic Glutamate 5)
0 (Receptors, Glutamate)
0 (Receptors, Metabotropic Glutamate)
0 (Receptors, N-Methyl-D-Aspartate)
0 (bcl-2-Associated X Protein)
6LR8C1B66Q (Dizocilpine Maleate)
8HW4YBZ748 (Oxidopamine)
E0399OZS9N (Cyclic AMP)

Date Created: 20110309 Date Completed: 20111018 Latest Revision: 20211020

20250114

10.1007/s11010-011-0773-x

21384157