Toll-like receptor 3 signaling attenuates liver regeneration.

Unlabelled: The current model for liver regeneration suggests that cell damage triggers Toll-like receptor (TLR) signaling via MyD88, leading to the induction of nuclear factor kappaB (NF-kappaB) and secretion of inflammatory cytokines that in turn prime liver regeneration. TLR3 is unique among TLRs in that it signals through TRIF (TIR domain-containing adaptor-inducing interferon-beta), not through MyD88, and may lead to activation of either the inflammatory or apoptotic pathway. The inflammatory pathway leads to NF-kappaB activation, whereas the apoptotic pathway, believed to be mediated by Rip3, leads to caspase-8 activation.

Deficits in social behavior and reversal learning are more prevalent in male offspring of VIP deficient female mice.

Blockage of vasoactive intestinal peptide (VIP) receptors during early embryogenesis in the mouse has been shown to result in developmental delays in neonates, and social behavior deficits selectively in adult male offspring. Offspring of VIP deficient mothers (VIP +/-) also exhibited developmental delays, and reductions in maternal affiliation and play behavior. In the current study, comparisons among the offspring of VIP deficient mothers (VIP +/-) mated to VIP +/- males with the offspring of wild type (WT) mothers mated to VIP +/- males allowed assessment of the contributions of both maternal and offspring VIP genotype to general health measures, social behavior, fear conditioning, and spatial learning and memory in the water maze.

ADNP differential nucleus/cytoplasm localization in neurons suggests multiple roles in neuronal differentiation and maintenance.

Complete deficiency in activity-dependent neuroprotective protein (ADNP) results in neural tube closure defects and death at gestation day 9 in mice. ADNP-deficient embryos exhibit dramatic increases in gene transcripts associated with lipid metabolism coupled to reduction in organogenesis/neurogenesis-related transcripts. In the pluripotent teratocarcinoma cell line P19, ADNP was shown to interact with specific chromatin regions in the neurodifferentiated state, which was associated with binding to the heterochromatin protein 1 alpha.

Blockage of VIP during mouse embryogenesis modifies adult behavior and results in permanent changes in brain chemistry.

Vasoactive intestinal peptide (VIP) regulates growth and development during the early postimplantation period of mouse embryogenesis. Blockage of VIP with a VIP antagonist during this period results in growth restriction, microcephaly, and developmental delays. Similar treatment of neonatal rodents also causes developmental delays and impaired diurnal rhythms, and the adult brains of these animals exhibit neuronal dystrophy and increased VIP binding.

Neurotrophic effects of the peptide NAP: a novel neuroprotective drug candidate.

This short review outlines the scientific progression from the neuropeptide vasoactive intestinal peptide as a neuroprotective agent that acts through glial cells to increase and modulate the synthesis and secretion of novel neuroprotective substances. Recent development in the studies on activity-dependent neuroprotective protein (ADNP) and activity-dependent neurotrophic factor (ADNF) and short peptide derivatives of these proteins, ADNF-9 and NAP suggest that these peptides are neurotrophic and promote neurite outgrowth. These short peptides hold promise in future neuroprotective/neurotrophic drug development.