Killick, R. | Search bioRxiv

bioRxiv2019

Identifying Novel Candidates for Re-Purposing as Potential Therapeutic Agents for Alzheimer’s disease

The current paper describes the identification of novel candidate compounds for repositioning as treatments for Alzheimers disease (AD) from the CMAP library. Candidate compounds were identified based on inverse correlation with transcriptome signatures developed from meta-analyses of Alzheimer RNA expression studies using the SPIED platform. The 78 compounds with a significant inverse correlation were taken forward into an in vitro programme using 6 well validated screening assays relevant to potential treatment targets in AD. Nineteen pf the compounds were hits in at least 2 of these assays. A description of each of these compounds is presented.

neuroscience↗

bioRxiv2019

Measuring vision using innate behaviours in mice with intact and impairedretina function

Measuring vision in rodents is a critical step for understanding vision, improving models of human disease, and developing therapies. Established behavioural tests for perceptual vision, such as the visual water task, rely on learning. The learning process, while effective for sighted animals, can be laborious and stressful in animals with impaired vision, requiring long periods of training. Current tests that that do not require training are based on sub-conscious, reflex responses (e.g. optokinetic nystagmus) that dont require involvement of visual cortex and higher order thalamic nuclei. A potential alternative for measuring vision relies on using visually guided innate defensive responses, such as escape or freeze, that involve cortical and thalamic circuits. In this study we address this possibility in mice with intact and degenerate retinas. We first develop automatic methods to detect behavioural responses based on high dimensional tracking and changepoint detection of behavioural time series. Using those methods, we show that visually guided innate responses can be elicited using parametisable stimuli, and applied to describing the limits of visual acuity in healthy animals and discriminating degrees of visual dysfunction in mouse models of retinal degeneration.

neuroscience↗