NEURONAL PHYSIOLOGY AND HIV-1 ASSOCIATED DEMENTIA

Project: Research project

Description

DESCRIPTION (Provided by applicant): The biochemical basis for cognitive decline in human immunodeficiency virus type one (HIV-1)-associated dementia (HAD) is a reversible selective neuronal impairment, caused as a consequence of brain mononuclear phagocyte (MP) viral infection and immune activation. This proposal addresses the overall question of how HIV-l infection in brain influences neural physiological processes that inevitably lead to neural dysfunction or death in HAD. Electrophysiological, pharmacological, immunological and molecular biological techniques will be directed toward three specific aims. 1) Determination of the relative contribution of viral (HIV-1) and cellular (MPderived) secretory factors on neural physiology. The hypothesis is that MP-secretions alter neuronal electrophysiological processes and modulate synaptic transmission and plasticity. These experiments will clarify the role of viral and cellular factors in HIV-1-induced neuronal and synaptic dysfunction or injury in HAD. 2) Identification of N-methyl-D-aspartate (NMDA) receptor subtypes involved in MP secretory product-induced neurotoxicity. We hypothesize that activation of specific NMDA receptors represent common mechanisms for MP-mediated neurodestruction during HAD. These studies will provide insights into molecular mechanisms of immune-associated neurodegeneration in HAD. 3) How alterations in cellular and synaptic occur by MP secretory factors in an animal model of HIV-1-encephalitis (HIVE). This study serves to cross-validate observations made in aims 1 and 2 and investigates the relationship between physiological alterations and disease. Overall, these studies are directed specifically towards understanding the role(s) that MP-secreted factors play in HAD and the mechanisms underlying HAD neuropathogenesis. In addition, these investigations can potentially provide opportunities for new drug intervention strategies.
StatusFinished
Effective start/end date6/15/018/31/12

Funding

  • National Institutes of Health: $298,308.00
  • National Institutes of Health: $305,487.00
  • National Institutes of Health: $30,217.00
  • National Institutes of Health: $184,375.00
  • National Institutes of Health: $289,657.00
  • National Institutes of Health: $17,001.00
  • National Institutes of Health: $184,375.00
  • National Institutes of Health: $289,657.00
  • National Institutes of Health: $289,657.00
  • National Institutes of Health: $184,375.00
  • National Institutes of Health: $371,250.00
  • National Institutes of Health: $184,375.00

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HIV-1
AIDS Dementia Complex
Dementia
Phagocytes
Macrophages
Voltage-Gated Potassium Channels
Microglia
Encephalitis
N-Methyl-D-Aspartate Receptors
Animal Models
Neurotoxins
Brain
Channelopathies
Pharmacology
Electrophysiological Phenomena
Neurons
Aptitude
Critical Pathways
Physiological Phenomena
Neuronal Plasticity

ASJC

  • Medicine(all)
  • Neuroscience(all)