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.