Cholinergic Receptor Alterations in the Brain Stem of Spinal Cord Injured Rats

• Published in: Neurochemical research 2013-02, Vol.38 (2), p.389-397
• Main Authors: Romeo, Chinthu, Raveendran, Anju Thoppil, Sobha, Nandhu Mohan, Paulose, Cheramadathukuzhiyil Scaria
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors; alpha7 Nicotinic Acetylcholine Receptor; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain Stem - metabolism; Cell Biology; Down-Regulation - physiology; Male; Neurochemistry; Neurology; Neurosciences; Original Paper; Protein Binding - physiology; Random Allocation; Rats; Rats, Wistar; Receptor, Muscarinic M1 - metabolism; Receptor, Muscarinic M3 - metabolism; Receptors, Cholinergic - metabolism; Receptors, Nicotinic - metabolism; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-012-0931-x

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.