Neurotransmitter Related Immunocytochemistry of the Human Central Nervous System

Summary

Immunocytochemical methods permit the precise anatomical study of neurotransmitter specific pathways in the human brain. It has been possible using antibodies to tyrosine hydroxylase (TH) to provide an atlas of human catecholaminergic (CA) neurons. A striking increase in complexity of CA neurons is seen in the human mesencephalon when compared with lower animals. Not only synthetic enzymes but also neurotransmitters themselves can be detected. Antibodies to the putative transmitter peptide substance P reveal its presence in axons and terminals. Areas of apparent interaction between systems can be studied and may give indications of distinct subdivisions within nuclei.

Alterations of specific neurons can be detected in human disease. It is possible to show increase in TH in the reduced numbers of sympathetic neurons in familial dysautonomia and to detect depletion of substance P containing primary sensory afferent terminals in this disease which is associated with decreased sensitivity to pain. Depletion of catechol-aminergic neurons is demonstrated in Parkinson’s disease.

Some neurotransmitters for which antibodies are available, notably serotonin, can be readily detected in animal tissue fixed by perfusion but, after death, rapidly diffuse away from their normal localization making their study virtually impossible in the human brain. Some antigens, such as TH, are present throughout the neuron in sufficient quantities to be immunocytochemically detectable; others, such as substance P, are detectable in axons and terminals but not (in the absence of colchicine treatment) in cell bodies.

Despite these difficulties immunocytochemistry has the potential of greatly increasing knowledge of human chemical neuroanatomy and pathology at the microscopic level of individual cells.