The raphe serotonin system was studied in patients with senile dementia of the Alzheimer type (SDAT) or with Parkinson's disease and compared with normal controls. Postmortem brain stems were cut in coronal sections from the red nucleus to the decussation of the pyramidal tract and were reacted with PH8 antibodies (PH8) which cross-react with tryptophan hydroxylase, the synthesizing enzyme for serotonin. In addition, adjacent sections were reacted with antibodies against tyrosine hydroxylase (TH) to detect catecholamine neurons in the locus ceruleus (LC), with monoamine oxidase (MAO) A antibodies, which labeled most neurons in the LC, or with MAO B antibodies which labeled a subpopulation of neurons in the raphe nuclei. A computer-based-image-analysis system was used for counting cell numbers and, in addition, 3-dimensional reconstructions of all raphe nuclei were made with this program. In SDAT, a loss of PH8-immunoreactive (PH8-i) neurons was detected in the raphe nuclei. This loss was most pronounced in the ventrolateral division of the dorsal raphe nucleus and was correlated to the cortical pathology and age of the patients. In addition the number of TH-immunoreactive (TH-i) neurons was reduced in the LC, with the rostral parts of the nucleus being the most severely affected. A comparison of the morphological changes in SDAT revealed that, in the same cases, the greatest neuronal alterations were found in the TH-i neurons in the LC rather than in the PH8-i neurons in the raphe nuclei. This reduction of TH-i neurons was matched by a loss of MAO A-immunoreactive (MAO A-i) neurons in the LC in SDAT. Similarly, the loss of PH8-i neurons was accompanied by a loss of MAO B-immunoreactive neurons in the raphe nuclei. In Parkinson's disease two different types of pathologies were found in the raphe nuclei; in one case with dementia a reduction of PH8-i neurons was seen in the ventrolateral and caudal subnucleus of the dorsal raphe. In two other cases with depression, severe cell loss was found in the raphe obscurus. All these Parkinson cases showed a considerable reduction of TH-i and MAO A-i neurons in the LC. Thus, the catecholamine lesions of the LC are more severe than the serotonin lesions of the raphe in SDAT patients and this was true of Parkinson patients as well. The relationships of catecholamine neurons with the MAO A enzyme localization and of serotonin neurons with the MAO B enzyme were also confirmed.

Keywords:
Immunocytochemistry, Locus ceruleus, Monoamine oxidase A and B, Noradrenaline, Quantitation
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© 1992 S. Karger AG, Basel
1992
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