Unveiling the role of monocytes in neurodegeneration using human brain organoid models 9369

Abstract Description Neurodegeneration is characterized by neuroinflammation, neuronal dysfunction,and death. Similarly, people living with HIV (PLWH) experience neuronal dysfunction, with around 50% developing HIV-associated neurocognitive disorders (HAND), despite effective viral suppression achieved by combined antiretroviral therapy. In HAND, peripheral immune cells such as monocytes infiltrate the central nervous system (CNS), altering homeostasis and causing inflammation. However, their role in neuropathogenesis is still unclear. To study these interactions, human cortical brain organoids were co-cultured with blood monocytes from PLWH – including Normal (N) and Cognitive Impaired (CI) – and HIV-negative controls, for 24 and 48 hours. Cell lysates were collected to quantify markers of neuronal function via western blot. Neuronal activity markers, synaptophysin and vGLUT1, showed slightly higher levels in co-cultured organoids HIV- monocytes when compared to HIV+ monocytes treated organoids. Co-cultured organoids with monocytes from HIV+ CI have similar levels of neuronal markers than the untreated control organoids. On the other hand, at 48H, MAP2 presented a slight decrease in HIV+ CI monocyte co-culture when compared to HIV+ and HIV- monocyte treated organoids. Further studies are being conducted, aiming mechanistically study the role of peripheral monocytes in neuronal activity. Funding Sources This work was funded by NIHMHD U54 MD007600, NINDS K22NS118975, 5R21NS131061-02, NIGMS PR-INBRE 5P20GM103475, The Alliance U54GM133807, HiREC S21MD001830. Topic Categories Neuroimmunology (NEUR)