NEUROBIOLOGY CORE PROJECT SUMMARY/ABSTRACT: The overall objective of the Neurobiology Core (NB) is to provide the NeuroAIDS community with a set of neurobiological resources that will enhance the analysis and discovery of the mechanisms of neurodegeneration associated with prolonged survival with HIV infection, from a comprehensive and dynamic perspective. The NB Core has been re-organized into In Vivo and In Vitro Units to better serve the current and future needs of the neuroAIDS field. The main resource objectives will be to: (a) provide a set of innovative state-of-the-art neuropathological and neurobiological in vivo and in vitro resources to support studies of the mechanisms of viral persistence/eradication, influence of microbiome in neuro-inflammation and role of aging in neurodegeneration with HIV infection, (b) encourage and facilitate collaborative work addressing these and other scientific themes of the Center, and (c) provide user training and consultation to new investigators. In addition, the NB Core Scientific objectives will include: (1) To provide support for studies of HIV infection in the CNS that address viral persistence and eradication, including molecular studies of chromatin modifiers, epigenetic markers and markers of viral production and cycling; (2) To provide in vitro and in vivo neuropathological resources and assays in support of the Microbiome theme, that could include studies of patterns of neuro-inflammation, neuro-vascular unit injury and gut pathology in patients with HAND; (3) To provide quantitative analysis of novel sets of HIV related neuropathologies in support of the theme on Aging. Examples of work on the Aging theme could include neuropathological and biochemical studies of: amyloid-? protein (A?) deposits including cerebral amyloid angiopathy; Tau and ?-synuclein accumulation; markers of autophagy and lysosomal activation; markers of mitochondrial biogenesis and mitophagy; brain immunophilin response; and human primary neuro-glial, brain endothelial and vascular smooth muscle cell cultures. And finally, (4) we will continue supporting clinico-pathological studies which investigate the relationship between new markers of neurodegeneration and HAND. Understanding the neuropathological basis for viral persistence and neural injury in the context of aging and the microbiome as contributing factors, will elucidate mechanisms through which HIV leads to HAND and inform new treatments for this disabling condition.