Neonatal hyperoxia in mice triggers long-term cognitive deficits via impairments in cerebrovascular function and neurogenesis.

Preterm birth is the leading cause of death in children under 5 years of age. Premature infants who receive life-saving oxygen therapy often develop bronchopulmonary dysplasia (BPD), a chronic lung disease. Infants with BPD are at a high risk of abnormal neurodevelopment, including motor and cognitive difficulties. While neural progenitor cells (NPCs) are crucial for proper brain development, it is unclear whether they play a role in BPD-associated neurodevelopmental deficits. Here, we show that hyperoxia-induced experimental BPD in newborn mice led to lifelong impairments in cerebrovascular structure and function as well as impairments in NPC self-renewal and neurogenesis. A neurosphere assay utilizing nonhuman primate preterm baboon NPCs confirmed impairment in NPC function. Moreover, gene expression profiling revealed that genes involved in cell proliferation, angiogenesis, vascular autoregulation, neuronal formation, and neurotransmission were dysregulated following neonatal hyperoxia. These impairments were associated with motor and cognitive decline in aging hyperoxia-exposed mice, reminiscent of deficits observed in patients with BPD. Together, our findings establish a relationship between BPD and abnormal neurodevelopmental outcomes and identify molecular and cellular players of neonatal brain injury that persist throughout adulthood that may be targeted for early intervention to aid this vulnerable patient population.

Maternal high-fat diet in mice induces cerebrovascular, microglial and long-term behavioural alterations in offspring.

Various environmental exposures during pregnancy, like maternal diet, can compromise, at critical periods of development, the neurovascular maturation of the offspring. Foetal exposure to maternal high-fat diet (mHFD), common to Western societies, has been shown to disturb neurovascular development in neonates and long-term permeability of the neurovasculature. Nevertheless, the effects of mHFD on the offspring's cerebrovascular health remains largely elusive. Here, we sought to address this knowledge gap by using a translational mouse model of mHFD exposure. Three-dimensional and ultrastructure analysis of the neurovascular unit (vasculature and parenchymal cells) in mHFD-exposed offspring revealed major alterations of the neurovascular organization and metabolism. These alterations were accompanied by changes in the expression of genes involved in metabolism and immunity, indicating that neurovascular changes may result from abnormal brain metabolism and immune regulation. In addition, mHFD-exposed offspring showed persisting behavioural alterations reminiscent of neurodevelopmental disorders, specifically an increase in stereotyped and repetitive behaviours into adulthood.

A practical approach to RT-qPCR-Publishing data that conform to the MIQE guidelines.

Given the highly dynamic nature of mRNA transcription and the potential variables introduced in sample handling and in the downstream processing steps (Garson et al. (2009)), a standardized approach to each step of the RT-qPCR workflow is critical for reliable and reproducible results. The MIQE provides this approach with a checklist that contains 85 parameters to assure quality results that will meet the acceptance criteria of any journal (Bustin et al. (2009)). In this paper we demonstrate how to apply the MIQE guidelines (www.rdml.org/miqe) to establish a solid experimental approach.

Mutation in the ap2-6 allele causes recognition of a cryptic splice site.

Mutations in the homeotic gene APETALA2 of Arabidopsis thaliana cause severe developmental alterations, most prominently homeotic floral organ replacements from petals to carpels and petals to stamens in the outer two floral whorls. To date, ten different alleles have been identified conferring phenotypes of various degrees. Of these ten alleles, only three have been characterized at the sequence level. The identification of the sequence alteration in the ap2-6 allele is reported here. In ap2-6 a single G.C to A.T transition occurred at the 3' end of intron 6 (position 1342) which leads to a dinucleotide loss at the mRNA level. This change is consistent with the G.C to A.T transition destroying a conserved dinucleotide motif (AG) required for proper splice recognition and with the resulting recognition of the next available downstream AG dinucleotide which in AP2 is immediately adjacent to the authentic 3' splice site. The dinucleotide loss will cause a frameshift, the translation of three incorrect amino acids and a premature stop codon resulting in a truncation of the AP2 sequence within the AP2-R2 domain. Such a truncation is predicted to impact severely on the function of AP2 and is consistent with the observed phenotype.