Substance use disorder (SUD) frequently co-occurs with comorbid conditions such as chronic pain or infection, however preclinical models typically investigate SUD in isolation. Our lab believes that developing complex models will yield greater insight into underlying mechanisms with implication for therapeutic development. This talk will describe aberrant cocaine-seeking behavior in dual mouse models of co-occurring cocaine use and HIV infection (EcoHIV infection of wild-type mice and HIV-1 infection of humanized mice). In particular, we identify increased resistance to extinction of cocaine seeking and elevated reinstatement. In addition, it will describe nucleus accumbens neuroimmune alterations and characterize astrocyte morphological consequences of infection. Finally, it will include data on the ability of a promising pharmacological target, troriluzole, to suppress reinstatement in control populations, with mitigated efficacy in the context of HIV.
Abstract: Alterations to brain vasculature are a noted feature of Alzheimer's disease and related dementias (ADRD). In some cases, dysfunction of brain vasculature, including changes to the blood-brain barrier and vascular inflammation, may precede other ADRD signatures. However, the mechanisms governing vascular pathology remain poorly understood. This talk will focus on SERPINA3, a serine protease inhibitor, as a key driver of brain vascular dysfunction under AD conditions, as determined using human induced pluripotent stem cell models, in vivo studies, and human tissue profiling.
Abstract: Join Dr. Jesús Torres-Vázquez for an engaging overview of how blood and lymphatic vessels develop and adapt in living organisms. Using transparent zebrafish embryos, live imaging, and powerful genetic tools, his laboratory explores how endothelial cells respond to developmental signals and mechanical forces from circulatory flow in health and disease. The talk will also introduce a novel technology to visualize tissue oxygenation at cellular resolution, opening exciting new possibilities for understanding development, hypoxia, cardiovascular disease, and cancer in both in vivo and in vitro models.
Abstract: Coleoid cephalopods are the only lineage outside of vertebrates to independently evolve large brains. Post-hatching, squid and octopus brains can grow over a thousandfold in a matter of weeks. We identify the source of these neurons in a collection of novel neurogenic tissues located entirely outside the brain. A custom, targeted spatial transcriptomics platform reveals a heterogeneous population of neural stem cells and progenitors within these tissues. We identify migratory routes that allow neuroblasts to continually populate lobes in the brain adjacent to the neuropil, creating an oldest-out layering of cell bodies within individual brain regions. Functional manipulations confirm that these tissues are both required and sufficient for proper neurogenesis post-hatching. This finding reveals a novel, cephalopod-specific developmental modality for large-scale adult neurogenesis, driving the expansion of the largest invertebrate brains, and provides a novel model for understanding how newborn neurons migrate to target locations and integrate into complex circuits.
