Immunocytochemical visualization of muscarinic cholinoceptors in the human cerebral cortex

The monoclonal antibody M 35 was used to study the cellular and subcellular distribution of muscarinic acetylcholine receptors in the human cerebral cortex. M 35, raised against purified muscarinic receptor protein, exerts muscarinic agonist-like effects at cholinergic synapses. Applied to human cortical tissue immediately fixed upon neurosurgical removal, light microscopically M 35 revealed immunoreactive perikarya predominantly of the pyramidal cell type in layers II/III and V, their labeled apical dendrites extending into the superficial layers. Furthermore, a smaller number of neurons of various non-pyramidal morphology in layers VI, IV and III was immunopositive. At the ultrastructural level, immunoprecipitate decorated distinct regions of the perikaryal cytoplasm, numerous dendritic profiles and synapses of both symmetric and asymmetric appearance. In the perikarya immunoprecipitate was associated with ribosomes, the endoplasmic reticulum and the Golgi apparatus. In dendrites the mierotubular system, in synaptic complexes the postsynaptic membranes were decorated. The results suggest that novel informations about the cell type specific and subcellular distribution of human muscarinic cholinoceptors can be obtained by M 35 immunocytochemistry

Muscarinic Cholinoceptive Neurons in the Frontal Cortex in Alzheimer’s Disease

The cellular distribution of muscarinic acetylcholine receptor protein in the frontal cortex of Alzheimer (AD) patients, age-matched and middle-aged controls was assessed quantitatively by means of immunohistochemistry using the monoclonal antibody M35. As shown previously in biopsy cortices, mainly layer II/III and V pyramidal neurons were immunolabeled. Neither distribution nor numbers of labeled cells displayed significant differences between the groups investigated. This is in accordance with the results of ligand binding studies that mostly failed to reveal different binding characteristics in AD compared to controls. Muscarinic and nicotinic receptor proteins have been shown to be colocalized in many cholinoceptive pyramidal neurons. Since nicotinic receptors-in contrast to muscarinic receptor proteins-are severely reduced in AD, this indicates a selective impairment of nicotinic receptor expression and not a significant death of cholinoceptive neurons per se.