Vasoactive intestinal peptide in the brain of a mouse model for Down syndrome.
The most common genetic cause of mental retardation is Down syndrome, trisomy of chromosome 21, which is accompanied by small stature, developmental delays, and mental retardation. In the Ts65Dn segmental trisomy mouse model of Down syndrome, the section of mouse chromosome 16 most homologous to human chromosome 21 is trisomic. This model exhibits aspects of Down syndrome including growth restriction, delay in achieving developmental milestones, and cognitive dysfunction. Recent data link vasoactive intestinal peptide malfunction with developmental delays and cognitive deficits. Blockage of vasoactive intestinal peptide during rodent development results in growth and developmental delays, neuronal dystrophy, and, in adults, cognitive dysfunction. Also, vasoactive intestinal peptide is elevated in the blood of newborn children with autism and Down syndrome. In the current experiments, vasoactive intestinal peptide binding sites were significantly increased in several brain areas of the segmental trisomy mouse, including the olfactory bulb, hippocampus, cortex, caudate/putamen, and cerebellum, compared with wild-type littermates. In situ hybridization for VIP mRNA revealed significantly more dense vasoactive intestinal peptide mRNA in the hippocampus, cortex, raphe nuclei, and vestibular nuclei in the segmental trisomy mouse compared with wild-type littermates. In the segmental trisomy mouse cortex and hippocampus, over three times as many vasoactive intestinal peptide-immunopositive cells were visible than in wild-type mouse cortex. These abnormalities in vasoactive intestinal peptide parameters in the segmental trisomy model of Down syndrome suggest that vasoactive intestinal peptide may have a role in the neuropathology of Down-like cognitive dysfunction.
Hill
Joanna M
JM
Section on Developmental and Molecular Pharmacology, NICHD, NIH, Bethesda, MD 20892, USA. jh139h@nih.gov
Ades
Anne M
AM
McCune
Susan K
SK
Sahir
Nadia
N
Moody
Elizabeth M
EM
Abebe
Daniel T
DT
Crnic
Linda S
LS
Brenneman
Douglas E
DE
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D012333:RNA, Messenger / Q000096:biosynthesis; D014314:Trisomy; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D012333:RNA, Messenger; D014660:Vasoactive Intestinal Peptide