Multiple Drug Treatments That Increase cAMP Signaling Restore Long-Term Memory and Aberrant Signaling in Fragile X Syndrome Models.

Fragile X is the most common monogenic disorder associated with intellectual disability (ID) and autism spectrum disorders (ASD). Additionally, many patients are afflicted with executive dysfunction, ADHD, seizure disorder and sleep disturbances. Fragile X is caused by loss of FMRP expression, which is encoded by the FMR1 gene. Both the fly and mouse models of fragile X are also based on having no functional protein expression of their respective FMR1 homologs. The fly model displays well defined cognitive impairments and structural brain defects and the mouse model, although having subtle behavioral defects, has robust electrophysiological phenotypes and provides a tool to do extensive biochemical analysis of select brain regions. Decreased cAMP signaling has been observed in samples from the fly and mouse models of fragile X as well as in samples derived from human patients. Indeed, we have previously demonstrated that strategies that increase cAMP signaling can rescue short term memory in the fly model and restore DHPG induced mGluR mediated long term depression (LTD) in the hippocampus to proper levels in the mouse model (McBride et al., 2005; Choi et al., 2011, 2015). Here, we demonstrate that the same three strategies used previously with the potential to be used clinically, lithium treatment, PDE-4 inhibitor treatment or mGluR antagonist treatment can rescue long term memory in the fly model and alter the cAMP signaling pathway in the hippocampus of the mouse model.

Atomic force microscopy: a tool for studying biophysical surface properties underpinning fungal interactions with plants and substrates.

One of the primary roles of the cell surface is to provide an effective barrier to various external environmental factors. Specifically, the surface properties of organisms serve as a critical obstacle to pathogen attack. Since its inception, Atomic Force Microscopy (AFM) has enabled nanoscale imaging of cell surfaces in their native state. However AFM has yet to be systematically applied toward resolving surface features and the forces underpinning plant-fungal interactions. In an effort to understand the physical forces involved at the plant-microbe interface, we describe a method for the attachment of fungal spores to AFM tips and the subsequent measurement of unbinding forces between spores with a range of substrates and plant surfaces under physiologically relevant conditions. Investigations of binding events using AFM offer an unexplored, sensitive, and quantitative method for analyzing host-pathogen/microbe-surface interactions.