title: Cholinergic receptor alterations in the brain stem of spinal cord injured rats.
abstract: Cholinergic receptors in upper motor neurons of brain stem control locomotion and coordination. Present study unravels cholinergic alterations in brain stem during spinal cord injury to understand signalling pathway changes which may be associated with spinal cord injury mediated motor deficits. We evaluated cholinergic function in brain stem by studying the expression of choline acetyl transferase and acetylcholine esterase. We quantified metabotropic muscarinic cholinergic receptors by receptor assays for total muscarinic, muscarinic M1 and M3 receptor subunits, gene expression studies using Real Time PCR and confocal imaging using FITC tagged secondary antibodies. The gene expression of ionotropic nicotinic cholinergic receptors and confocal imaging were also studied. The results from our study showed metabolic disturbance in cholinergic pathway as choline acetyl transferase is down regulated and acetylcholine esterase is up regulated in spinal cord injury group. The significant decrease in muscarinic receptors showed by decreased receptor number along with down regulated gene expression and confocal imaging accounts for dysfunction of metabotropic acetylcholine receptors in spinal cord injury group. Ionotropic acetylcholine receptor alterations were evident from the decreased gene expression of alpha 7 nicotinic acetylcholine receptors and confocal imaging. The motor coordination was analysed by Grid walk test which showed an increased foot slips in spinal cord injured rats. The significant reduction in brain stem cholinergic function might have intensified the motor dysfunction and locomotor disabilities.
authors.affiliation: Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Kochi 682 022, Kerala, India.
authors.forename: Chinthu
authors.initials: C
authors.lastname: Romeo
authors.forename: Anju Thoppil
authors.initials: AT
authors.lastname: Raveendran
authors.forename: Nandhu Mohan
authors.initials: NM
authors.lastname: Sobha
authors.forename: Cheramadathukuzhiyil Scaria
authors.initials: CS
authors.lastname: Paulose
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D008297:Male; D011485:Protein Binding / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579165:Chrna7 protein, rat; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor