The Wu Lab applies advanced neuroimaging techniques to various animal models. We first validated alterations in the diffusion function with histological evidence using the shaking pup, a canine model of dysmyelination for human multiple sclerosis (Wu et al., NeuroImage 2011). More recently, we have studied volumetric changes (Grecco et al., eLife 2021) and diffusion microstructural changes using the NODDI metrics (Grecco et al., Scientific Reports 2022) in mouse brains of prenatal methadone exposure. For Alzheimer’s disease, we have explored brain atrophy in a mouse model of PS19 tauopathy using volumetric imaging with ROI-based and voxel-based analyses (Martinez et al., Nature neuroscience 2022). Our lab leads the neuroimaging component in a multicenter project (i.e., Immune-AD R01AG022304-15S1) to study the microstructural and capillary perfusion in an animal model of Alzheimer’s disease with exercise intervention. We also support the Model-AD U54 project characterizing small animal models of Alzheimer’s disease.
Synaptic structure and function are the keys to several neurodegenerative disorders, including Alzheimer’s disease. Specifically, dysfunctional synapses and dysregulated synaptic plasticity in the hippocampus are responsible for early memory and cognitive decline in Alzheimer's disease. For a decade, invasive tools, such as electrophysiological or immunohistochemical techniques, have been developed to study synaptic morphology and density in animal models or human postmortem brain samples. Nevertheless, it has been challenging to study synaptic structure in living humans. Our lab received NIH R01 award to use a rodent model of Alzheimer’s disease (i.e., 5xFAD) to validate the diffusion imaging metric with synaptic density measured by autoradiography with a radioactive synaptic protein-binding tracer (UCB-J) and by histology with immunohistochemistry.
