Dec 15, 2017

Effect of J147 on Alzheimer's disease in Transgenic Mice

Randina Friestad '18

Alzheimer’s is a vicious disease that accounts for 50-70% of all diagnosed dementias. The main focus in Alzheimer’s disease (AD) research, has historically been in preventative treatments modalities, but rarely treatments post diagnosis, especially in late stages of the disease. The goal of this study was to determine the viability of the neurotrophic molecule J147 in diminishing symptoms of AD. In this study, AD was induced in Transgenic mice. A series of cognitive test were utilized to demonstrate how J147 treatments affected memory and cognitive ability in the mice. J147 treatment was found to be effective in improving memory along with nerve growth. Nerve growth factor and brain derived neurotrophic factor was increased in the treated mice brains. This research could be an effective tool in restoring memory and motor skills to individuals affected by AD.

Genomic Evidence for Syncytin Gene Decay Across Simian Species*

Madeline Reding '18

The syncytin family of genes originate from env retroviral genes, and by definition, are highly conserved in mammalian species, are expressed in the placenta, and encode proteins that enable cell-to-cell fusion. This fusion activity is central to their function in placental development; in mice without functional syncytins, there are defects in cell-to-cell fusion, impairing maternal-fetal exchange of nutrients. Though they are essential for placental formation, the oldest discovered syncytin genes were acquired 10-80mya, while mammals emerged around 225mya. In their 2013 paper, “Differential Evolutionary Fate of an Ancestral Primate Endogenous Retrovirus Envelope Gene,” Cecile Esnault et al. propose that over the course of placental mammal evolution, older env syncytin genes were replaced by others, as a result of more recent retroviral infections, with these older syncytin genes losing function over time due to lack of evolutionary pressure. Thus, they hypothesize, there should be genomic evidence of these decaying syncytin genes in mammalian genomes. To address this question, Esnault et al. examined the sequence and properties of the envV2 gene across simian species. Quantitative RT-PCR and in situ hybridization were used to examine envV2 expression in different tissue types, showing that in simians as diverse as humans and macaques, the envV2 gene is expressed preferentially in placental tissues, specifically in the syncytiotrophoblast layer. To examine fusogenic properties, non-placental cell lines were transfected with envV2 genes from different simians. In this assay,envV2 genes from all tested Old World simians were highly fusogenic, some New World monkey and hominoid genes were, and humans envV2 genes were not. The apparent loss of fusogenic activity, even while maintaining expression patterns, supports the decaying syncytin hypothesis. However, other possible functions of the gene require further study to conclude a loss of overall function.