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Expression of the endoplasmic reticulum stress response marker, BiP, in the central nervous system of HIV‐positive individuals
Author(s) -
Lindl K. A.,
Akay C.,
Wang Y.,
White M. G.,
JordanSciutto K. L.
Publication year - 2007
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/j.1365-2990.2007.00866.x
Subject(s) - microglia , endoplasmic reticulum , biology , unfolded protein response , neurodegeneration , immunofluorescence , oxidative stress , atf6 , microbiology and biotechnology , excitotoxicity , immunology , inflammation , pathology , antibody , programmed cell death , medicine , endocrinology , apoptosis , biochemistry , disease
The prevalence of HIV‐associated neurocognitive impairment (NCI), which includes HIV‐associated dementia (HAD) and minor cognitive and motor disorder (MCMD), has been increasing. HIV‐infected and/or activated macrophages/microglia in the brain initiate the neurodegeneration seen in HIV‐associated NCI via soluble neurotoxic mediators, including reactive oxygen species, viral proteins and excitotoxins. Neurotoxic factors released by macrophages/microglia injure neurones directly and alter astrocytic homeostatic functions, which can lead to excitotoxicity and oxidative stress‐mediated neuronal injury. Often, cells respond to oxidative stress by initiating the endoplasmic reticulum (ER) stress response. Thus, we hypothesize that ER stress response is activated in HIV‐infected cortex. We used immunofluorescence and immunoblotting to assess expression patterns of the ER stress proteins, BiP and ATF6, in HIV‐positive cortical autopsy tissue. Additionally, we performed immunofluorescence using cell type‐specific markers to examine BiP staining in different cell types, including neurones, astrocytes and macrophages/microglia. We observed a significant increase in BiP expression by both immunoblotting and immunofluorescence in HIV‐positive cortex compared with control tissue. Additionally, phenotypic analysis of immunofluorescence showed cell type‐specific increases in BiP levels in neurones and astrocytes. Further, ATF‐6β, an ER stress response initiator, is up‐regulated in the same patient group, as assessed by immunoblotting. These results suggest that ER stress response is activated in HIV‐infected cortex. Moreover, data presented here indicate for the first time that numbers of macrophages/microglia increase in brains of MCMD patients, as has been observed in HAD.