vasoactive-intestinal-peptide and Intellectual-Disability

To estimate the associations between polymorphisms in neuronal homeostasis, neuroprotection, and oxidative stress candidate genes and neurodevelopmental disability.. This was a nested case-control analysis of a randomized trial of magnesium sulfate administered to women at imminent risk for early (before 32 weeks) preterm birth for the prevention of death or cerebral palsy in their offspring. We evaluated 21 single-nucleotide polymorphisms (SNPs) in 17 genes associated with neuronal homeostasis, neuroprotection, or oxidative stress in umbilical cord blood. Cases included infant deaths (n=43) and children with cerebral palsy (n=24), mental delay (Bayley Mental Developmental Index less than 70; n=109), or psychomotor delay (Bayley Psychomotor Developmental Index less than 70; n=91) diagnosed. Controls were race-matched and sex-matched children with normal neurodevelopment. Associations between each SNP and each outcome were assessed in logistic regression models assuming an additive genetic pattern, conditional on maternal race and infant sex, and adjusting for study drug assignment, gestational age at birth, and maternal education.. The odds of cerebral palsy were increased more than 2.5 times for each copy of the minor allele of vasoactive intestinal polypeptipe (VIP, rs17083008) (adjusted odds ratio 2.67, 95% confidence interval 1.09-6.55, P=.03) and 4.5 times for each copy of the minor allele of N-methyl-D-aspartate receptor subunit 3A (GRIN3A, rs3739722) (adjusted odds ratio 4.67, 95% CI 1.36-16.01, P=.01). The association between the advanced glycosylation end product-specific receptor (AGER, rs3134945) SNP and mental delay was modulated by study drug allocation (P=.02).. Vasoactive intestinal polypeptipe and GRIN3A SNPs may be associated with cerebral palsy at age 2 in children born preterm.

Topics: Case-Control Studies; Cerebral Palsy; Child, Preschool; Developmental Disabilities; Female; Genetic Markers; Homeostasis; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intellectual Disability; Logistic Models; Male; Oxidative Stress; Polymorphism, Single Nucleotide; Psychological Tests; Psychomotor Disorders; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Receptors, N-Methyl-D-Aspartate; Vasoactive Intestinal Peptide

Stearyl-Nle-VIP (SNV) is a novel agonist of vasoactive intestinal peptide (VIP) exhibiting a 100-fold greater potency than the parent molecule and specificity for a receptor associated with neuronal survival. Here, the developmental and protective effects of SNV were investigated in vivo using two models of developmental retardation, hypoxia and cholinergic blockade. In both cases chronic administration of SNV during development provided protective effects. Water maze experiments on the weaned animals have demonstrated a prophylactic action for SNV and enhancement of spatial memory in animals exposed to a cholinotoxin. SNV may act by providing neuroprotection, thereby improving cognitive functions. This work is dedicated to Prof. R.J. Wurtman whose inspiration and leadership in the field of neuroscience and cognition is beyond comparison.

Topics: Aging; Animals; Aziridines; Choline; Hypoxia; Intellectual Disability; Male; Maze Learning; Memory; Neuromuscular Blocking Agents; Neurotoxins; Rats; Space Perception; Vasoactive Intestinal Peptide