Vasoactive Intestinal Peptide in Neurodevelopmental Disorders:Therapeutic Potential

Abstract

Abstract:Vasoactive intestinal peptide (VIP) mediates important events during the development of the nervous system. VIP can stimulate neuronogenesis as well as differentiation and neurite outgrowth; it can promote the survival of neurons and assist in neuronal repair; it is also anti-inflammatory and can modulate immune responses. In addition, VIP is necessary for the normal growth and development of the early postimplantation mouse embryo during the period when the major embryonic events are neural tube formation, neuronogenesis and expansion of the vascular system. Receptors for VIP appear during early postimplantation embryogenesis in the rodent and exhibit changing localization patterns throughout the development of the brain. During embryogenesis, unregulated VIP may have major and permanent consequences on the formation of the brain and may be a participating factor in disorders of neurodevelopment. VIP has been linked to autism, Down syndrome and fetal alcohol syndrome. This paper will review the role of VIP in neurodevelopment, its known involvement in neurodevelopmental disorders and propose ways in which VIP might be of therapeutic value.

The Expression of Vasoactive Intestinal Polypeptide in Visual Cortex-17 in Normal Visual Development and Formation of Anisometropic Amblyopia

“…While not extensively studied in central neurons, VIP is a neurotrophic factor that can regulate neural growth, migration, and process formation. [29][30] In our current study, we deduced that abnormal visual stimulation may reduce the production of endogenous VIP, and then the cortical energy metabolism and the supply of metabolic substrates are influenced. Confirmed in the present study is that asymmetrical visual stimulation during the development of the visual cortex may cause amblyopia through reduction of VIP synthesis in the cortex.…”

Differential Regulation of Vasoactive Intestinal Peptide (VIP) in the Dentate Gyrus and Hippocampus via the NO-cGMP Pathway Following Kainic Acid-Induced Seizure in the Rat

“…During development, VIP promotes neurogenesis, differentiation of other cell types in the nervous system, neurite outgrowth, and mediates neuronal survival (Hill 2007). We have previously shown that ADNP expression increases in the SGZ of the DG (Cosgrave et al 2008), the site of adult neurogenesis, suggesting that it may play an important role in neurogenesis.…”

Therapeutic Potential of Vasoactive Intestinal Peptide and its Receptors in Neurological Disorders

“…In mice, a deficit in social behavior has been observed following a blockage of VIP during neural tube closure. This is analogous to the period in human development during which the improper neural development resulting in ASD is thought to occur [59]. Therefore, the strong associations between VIP and ASD suggest that this pluripotent peptide could have pharmacotherapeutic potential.…”

“…Studies of affected families and twins have indicated that ASD is highly genetic, as the relative risk of having a second child with ASD, particularly if both children are male, is 20–50 times higher than the population base rate [58]. In terms of environmental causes, incidents of ASD have been linked to thalidomide or valproic acid exposure, prenatal alcohol use, infections, and vaccinations [59]. However, it is likely that susceptibly to ASD is due to many interacting genes with the resulting phenotype modified by complex environmental factors [60].…”

“…For example, levels of neuropeptides, such as VIP, calcitonin gene-regulating peptide, brain-derived neurotrophic factor (BDNF), and neurotrophin 4/5 were higher than normal in the blood of newborns who were later diagnosed with ASD or mental retardation [61]. Likewise, an additional link between VIP and ASD is exemplified in a subset of ASD individuals who suffer from inflammatory bowel disorders, as VIP is an important gut peptide and immunomodulatory factor [59]. There is also evidence to suggest a connection between polymorphisms in the upstream region of the VPAC2 receptor gene with the gastrointestinal and stereotypical behaviors observed in autistic patients.…”