vasoactive-intestinal-peptide and Developmental-Disabilities

A hallmark in most neurological disorders is a massive neuronal cell death, in which uncontrolled immune response is usually involved, leading to neurodegeneration. The vasoactive intestinal peptide (VIP) is a pleiotropic peptide that combines neuroprotective and immunomodulatory actions. Alterations on VIP/VIP receptors in patients with neurodenegerative diseases, together with its involvement in the development of embryonic nervous tissue, and findings found in VIP-deficient mutant mice, have showed the relevance of this endogenous peptide in normal physiology and in pathologic states of the central nervous system (CNS). In this review, we will summarize the role of VIP in normal CNS and in neurological disorders. The studies carried out with this peptide have demonstrated its therapeutic effect and render it as an attractive candidate to be considered in several neurological disorders linked to neuroinflammation or abnormal neural development.

Topics: Alzheimer Disease; Animals; Autistic Disorder; Brain; Brain Injuries; Developmental Disabilities; Down Syndrome; Encephalitis; Female; Fetal Alcohol Spectrum Disorders; Humans; Mice; Multiple Sclerosis; Nervous System Diseases; Neuroprotective Agents; Parkinson Disease; Pregnancy; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide

GABAergic interneurons play important roles in cortical circuit development. However, there are multiple populations of interneurons and their respective developmental contributions remain poorly explored. Neuregulin 1 (NRG1) and its interneuron-specific receptor ERBB4 are critical genes for interneuron maturation. Using a conditional ErbB4 deletion, we tested the role of vasoactive intestinal peptide (VIP)-expressing interneurons in the postnatal maturation of cortical circuits in vivo. ErbB4 removal from VIP interneurons during development leads to changes in their activity, along with severe dysregulation of cortical temporal organization and state dependence. These alterations emerge during adolescence, and mature animals in which VIP interneurons lack ErbB4 exhibit reduced cortical responses to sensory stimuli and impaired sensory learning. Our data support a key role for VIP interneurons in cortical circuit development and suggest a possible contribution to pathophysiology in neurodevelopmental disorders. These findings provide a new perspective on the role of GABAergic interneuron diversity in cortical development. VIDEO ABSTRACT.

Topics: Action Potentials; Animals; Animals, Newborn; Calcium; Cerebral Cortex; Developmental Disabilities; Disease Models, Animal; Gene Expression Regulation, Developmental; Homeodomain Proteins; In Vitro Techniques; Interneurons; Mice; Mice, Transgenic; Patch-Clamp Techniques; Photic Stimulation; Receptor, ErbB-4; Signal Detection, Psychological; Somatostatin; Spectrum Analysis; Vasoactive Intestinal Peptide; Visual Pathways

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