Muscarinic, N-methyl- d-aspartate (NMDA) and benzodiazepine receptor binding sites in cortical membranes from amyotrophic lateral sclerosis patients

• Published in: Journal of the neurological sciences Vol. 143; no. 1; pp. 121 - 125
• Main Authors: Gredal, Ole, Pakkenberg, Bente, Nielsen, Mogens
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.11.1996; Elsevier Science
• Subjects: Aged; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - metabolism; Benzodiazepine receptor; Binding Sites - physiology; Biological and medical sciences; Brain Chemistry - physiology; Cortex; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dizocilpine Maleate - metabolism; Dizocilpine Maleate - pharmacology; Excitatory Amino Acid Antagonists - metabolism; Excitatory Amino Acid Antagonists - pharmacology; Female; Flumazenil - metabolism; Flumazenil - pharmacology; GABA Modulators - metabolism; GABA Modulators - pharmacology; Humans; Male; Medical sciences; Middle Aged; Motor cortex; Motor Cortex - chemistry; Muscarinic; Muscarinic Antagonists - metabolism; Muscarinic Antagonists - pharmacology; Neurology; NMDA receptor; Quinuclidinyl Benzilate - metabolism; Quinuclidinyl Benzilate - pharmacology; Radioligand Assay; receptor; Receptor binding; Receptors, GABA-A - analysis; Receptors, GABA-A - metabolism; Receptors, Muscarinic - analysis; Receptors, Muscarinic - metabolism; Receptors, N-Methyl-D-Aspartate - analysis; Receptors, N-Methyl-D-Aspartate - metabolism; Tritium; Muscarinic; receptor; Motor cortex; Cortex; Amyotrophic lateral sclerosis; Benzodiazepine receptor; Receptor binding; NMDA receptor; Human; Nervous system diseases; Pathophysiology; Central nervous system disease; Degenerative disease; Muscarinic receptor; Spinal cord disease
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/S0022-510X(96)00196-7

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder causing marked pathology in the motoneuron system. The pathophysiology of the selective degeneration of motor neurons in the disease is as yet unknown, but evidence suggests that excitotoxic mechanisms might be involved. The present study was undertaken to determine whether defects in neurotransmitter receptors are involved in the disease, analyzing uniformly sampled specimens from neocortex and motorcortex. The binding to benzodiazepine, muscarinic cholinergic, and NMDA receptors in ALS brains was compared to that in control brains, using a single radioligand concentration of [ 3H]Ro 15-1788, [ 3H]QNB and [ 3H]MK-801. The benzodiazepine and the muscarinic cholinergic receptor binding was unaffected in any cortical region from the ALS subjects compared to controls. NMDA receptor binding labeled by [ 3H]MK-801 was significantly increased in several neocortical regions in the ALS group compared to the control group. Scatchard analysis of [ 3H]MK-801 binding in frontal cortex revealed a single binding site with an unaltered maximal binding capacity but an increased binding affinity of the site in the ALS group compared to the controls. The generalized alteration in the affinity of the binding site for [ 3H]MK-801 in the ALS cortex may indicate a modification of the NMDA receptor due to different sensitivity for endogenous modulators or to a different subunit composition of the NMDA receptor in ALS with altered functional properties. These findings may reflect a pathophysiological phenomenon in ALS.