Seminar: Robyn Klein

Virus-mediated cognitive impairment

This presentation will focus on how emerging RNA viral infections and systemic inflammation drive cognitive deficits.  Neurotropic flaviviruses (WNV and ZIKV) and neurovirulent coronavirus (SARS-CoV-2) induce blood-brain barrier (BBB) dysfunction and the CNS entry of mononuclear cells within the hippocampus, a forebrain structure in which memory formation occurs via strengthening of new synapses and the generation of new neurons. Using animal models with validation in human tissue, the Klein lab has defined mechanisms that alter BBB permeability, and impairments in learning and memory using transcriptomic, cell biologic, and behavioral approaches. These mechanisms include activation of GPCRs (S1PR2) and innate immune receptors (IL-1R1, C3aR, TNFR1) on resident neural cells, including neural stems cells, microglia, astrocytes and neurons, that lead to synapse elimination and loss of neurogenesis within the adult hippocampus. Targeting these receptors via genetic or pharmacologic manipulation during acute infections can prevent memory impairments during and after recovery.