Human striatum: Chemoarchitecture of the caudate nucleus, putamen and ventral striatum in health and Alzheimer's disease

N. Selden, C. Geula, L. Hersh, M. M. Mesulam

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101 Scopus citations

Abstract

The morphology and distribution of perikarya positive for choline acetyltransferase, somatostatin, calcium binding protein (calbindin D28K) and nicotinamide adenine dinucleotide phosphate diaphorase were surveyed in the human striatum. Choline acetyltransferase and somatostatin antibodies labeled separate populations of large striatal interneurons. Somatostatin immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (nitric oxide synthase) activity were completely co-localized. Calbindin antibody identified two distinct groups of striatal neurons: (1) numerous medium-sized, lightly stained neurons, probably analogous to striatopallidal projection neurons in the rat, and (2) much less numerous, large, darkly stained neurons. Half of the latter group, but none of the former, were also nicotinamide adenine dinucleotide phosphate diaphorase-positive. Somatostatin-positive and medium-sized, calbindin-positive neurons were more numerous in the caudate nucleus than in the putamen or ventral striatum. By contrast, large calbindin-immunoreactive neurons were more frequently encountered in the putamen. Choline acetyltransferase-positive neurons were evenly distributed across striatal components. In aged control subjects, the size of large, darkly stained calbindin-positive neurons was reduced relative to young subjects. Aging had no effect on somatostatin-, medium-sized calbindin-, or choline acetyltrans-ferase-positive neurons. However, in histologically confimed cases of Alzheimer's disease, there was a selective, 75% loss of choline acetyltransferase-immunoreactive perikarya from the ventral striatum, but not from the dorsal striatum, compared to aged controls. Furthermore, the remaining cholinergic neurons in the ventral striatum of Alzheimer's disease cases were significantly smaller than similar neurons in controls. These results indicate that various striatal components which have been shown to differ in their anatomical connectivity and functional specialization, also differ in their neurochemical signatures. The specific and marked loss of choline acetyltransferase-positive neurons from the ventral striatum in Alzheimer's disease is consistent with the characteristic cholinergic and 'limbic' pathology in this disease.

Original languageEnglish
Pages (from-to)621-636
Number of pages16
JournalNeuroscience
Volume60
Issue number3
DOIs
StatePublished - Jun 1994

Bibliographical note

Funding Information:
This and various other studiesa greet hat ChAT- positive neurons and cholinergic activity in the caudate nucleus and putamen are not affectedb y AD.8.54,79’I”n keeping with Lehericy et al.,79 the presents tudy demonstratesa 74% reduction in the density of large, ChAT-immunoreactiven eurons in the ventral striatumo f AD patients,c omparedw ith agedc ontrols. This effectc ould reflectt he deatha nd thus absence of many cholinergic striatal inter-Acknowledgements-We thank L. Christie, K. Bouve and neurons.A lternatively,o nly the expressiono f ChAT M. Celio and R. Benoit for the generous donation, respect-T. Hashimi for expert secretarial and technical support and in thesen eurons, and not the neurons themselves, ively, of calbindin and somatostatin antibodies. This work might be lost.79H owever,t he reduceds ize of ChAT-was supported in part by a Javits Neuroscience investigator immunoreactiven eurons in the ventral striatum of Award (NSZOZSS), an AIzheimer’s Research Center Grant AD casess uggestst hat theser emaining choline&c (AGO5 I34), and grants from the American Federation for neurons continue to expressh igh levels of ChAT (AG10282). N. Selden was supported by an American Aging Research and the National Institute on Aging even after presumablyb eing affectedb y the disease Federation for Aging Research/Hartford Foundation process. Scholarship.

ASJC Scopus subject areas

  • Neuroscience (all)

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