Selective retardation of the development of the basal forebrain cholinergic and pontine catecholaminergic nuclei in the brain of trisomy 16 mouse, an animal model of Down's syndrome

J. Kiss, M. Schlumpf, R. Balázs

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Brain development, examined at embryonic day 17, was retarded in murine trisomy 16 (Ts16). Ts16 is considered to serve as a model of the human trisomy 21 (Down's syndrome) by virtue of the presence in the mouse chromosome 16 of a set of genes located in humans in the segment of chromosome 21 that is requisite to produce the phenotypic features of Down's syndrome when present in triplicate. In addition to a reduction in brain size and cortical thickness, we observed a severe reduction throughout the brain in the density of muscarinic receptors, assessed by autoradiographic detection of specifically bound tritiated N-methyl-scopolamine, and by the failure of the development of the differentiated pattern of receptor distribution in the brainstem. The effect of gene dosage was also examined on specific neuronal populations. The distribution of acetylcholine esterase (AChE)-, tyrosine hydroxylase (TH)- and 5-hydroxytryptamine (5-HT)-positive cells in the trisomic brain was similar to that observed in chromosomally balanced littermates. On the other hand, the number of AChE-positive cells was 60-70% of the estimates in littermate controls in regions containing the septum, the vertical and horizontal limbs of the diagonal band and the basal forebrain cholinergic nuclei. Similarly, the number of TH-positive cells was reduced by about 30% in the pons. In contrast, in the trisomic foetuses the number of TH-positive cells in the mesencephalon and the diencephalon was similar to that in littermate controls, while that of 5-HT-positive cells in the mesencephalic nuclei was only slightly affected, if at all. Ts16 results, therefore, in a selective retardation of some neuronal systems, and this may lead to a perturbation of brain development. Furthermore, the systems whose development was retarded selectively are those which in Down's syndrome adults exhibit pronounced deficits of cells that - in case the murine Ts16 is a valid model - may also involve developmental disorders.

Original languageEnglish
Pages (from-to)251-264
Number of pages14
JournalDevelopmental Brain Research
Volume50
Issue number2
DOIs
Publication statusPublished - Dec 1 1989

Keywords

  • Basal forebrain cholinergic cell
  • Brain development
  • Catecholaminergic system
  • Down's syndrome
  • Locus ceruleus
  • Murine trisomy 16
  • Muscarinic cholinergic receptor autoradiography
  • Serotoninergic system

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology

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