Basic Research Studies > HIV
and the Brain
HIV and the Brain
Human immunodeficiency virus type-1 (HIV-1) infection is
the most common cause of dementia in adults younger than
40 years of age. In fact, many patients infected with HIV-1
suffer cognitive impairment, including subcortical dementia
with psychomotor slowing, but also Parkinsonism and behavorial
abnormalities including psychosis and depression. HIV dementia
may result from neuronal death in the basal ganglia, cerebral
cortex, and hippocampus. HIV-1 does not kill neurons by infecting
them, but rather viral proteins released from infected glial
cells, macrophages, and/or stem cells may kill neurons directly
or may increase their vulnerability to other cell death stimuli.
It has been suggested that the biochemical and molecular
cascades by which neurons become dysfunctional and die in
HIV dementia are similar to those that occur in Alzheimer's
disease (gp120 and Tat initiating apoptosis, excitoxicity
, and inflammation in HIVdementia while beta- amyloid protein
could have a similar role in Alzheimer's disease). Because
antiretroviral agents are insufficient in the treatment of
HIV dementia, neuroprotective (e.g., excitatory amino-acid
receptor antagonists, antioxidants, and calcium-stabilizing
agents) as well as anti-inflammatory approaches are necessary
in addition to drugs that reduce viral load. On-going research
projects involve 1) providing neuroprotection based on a
SV40-mediated gene delivery of anti-oxidants agents (e.g.,
SOD, GPx , catalase ) to the brain regions more susceptible
to the toxic effects of the viral proteins (striatum, hippocampus);
and 2) developing a cell therapy approach by using bone marrow
stem cells transduced in situ in vivo by a SV40-based vector,
in order to study if the putative migration of these stem
cells into the CNS and their differentiation under different
circumstances (e.g., different growth factors, chemokines
, cytokines), may allow them to replenish the cells that
died after the viral injury.
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