Neurochemical Changes in Murine Trisomy 16: Delay in Cholinergic and Catecholaminergic Systems |
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Authors: | P T Ozand R L Hawkins R M Collins Jr W D Reed P J Baab M L Oster-Granite |
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Institution: | W.P.C.C. Down's Syndrome Center, Department of Pediatrics, and Department of Anatomy, University of Maryland School of Medicine, Baltimore, Maryland, U.S.A. |
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Abstract: | Abstract: Two strains of Mus musculus musculus , C57BL/6J and CD-1, and Mus musculus poschiavinus , the tobacco mouse, were used to study the effects of increased gene dosage of mouse chromosome 16 (MMU 16). A developmental delay has been found in the brains of murine trisomy 16 (Ts 16) fetuses. Both the brain weight (in all three strains) and DNA content (in CD-1) were reduced, while protein content was unchanged in Ts16 compared to normal littermates. The daily increments of weight and protein (except in M. m. poschiavinus ) were significantly greater in Ts16. The activities of choline acetyltransferase and acetylcholinesterase and nuscarinic receptor binding were reduced. Their daily increments were also reduced to less than 56% that of littermates in Ts16 brains. The rate limiting enzymes of Catecholaminergic neurons, tyrosine hydroxylase and do-pamine β-hydroxylase, and the concentration of catecholamines in the brains of Ts16 animals were lower. The activities of three other Catecholaminergic enzymes, DOPA decarboxylase, catechol O -methyltransferase, and monoamine oxidase, were generally elevated in Ts16 brain, as were their daily increments. These observations indicate a significant developmental alteration in the maturation of the trisomic brain and suggest future avenues for defining the effect of increased gene dosage of MMU 16 in the CNS. |
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Keywords: | Trisomy 16 Mouse-Down's syndrome Cholinergic development Catecholaminergic development |
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