TY - JOUR
T1 - SDF-1α is expressed in astrocytes and neurons in the AIDS dementia complex
T2 - An in vivo and in vitro study
AU - Rostasy, Kevin
AU - Egles, Christophe
AU - Chauhan, Ashok
AU - Kneissl, Michelle
AU - Bahrani, Padmanabhan
AU - Yiannoutsos, Constantin
AU - Hunter, Dale D.
AU - Nath, Avindra
AU - Hedreen, John C.
AU - Navia, Bradford A.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - Recent in vitro studies suggest that the alpha chemokine stromal-derived factor-1α (SDF-1α) and its receptor CXCR-4 may contribute to neuronal apoptosis in HIV infection of the brain. The cellular and regional expression of this chemokine and its relationship to the AIDS dementia complex (ADC), however, have remained undetermined. Using immunohistochemistry and semiquantitative RT-PCR, we examined the expression of SDF-1α in the frontal cortex (FC), the adjacent deep white matter (DWM), and the basal ganglia (BG) of 17 patients with ADC and 5 normal controls, and the FC and temporal cortex of 6 patients with Alzheimer disease (AD). Additionally, SDF-1α expression was studied in 3 different neuronal cultures: differentiated SK-N-MC cells, primary human fetal neuronal, and mouse hippocampal cultures. SDF-1α staining was predominantly localized to astrocytes in all 3 groups in the gray matter of the FC and the BG, often in the vicinity of cortical and basal ganglia neurons, but was generally absent in the DWM. Further, the number of positive neurons was significantly greater in the BG of AIDS subjects with advanced brain disease compared to subjects with lesser disease (p = 0.029). All cultures showed prominent SDF-1α staining of neurons within the cytoplasm and in neurites, whereas preferential expression in GABA-ergic neurons was found in hippocampal cultures. This is the first study to show that SDF-1α is constitutively expressed in astrocytes of the deep and cortical gray matter as well as in neurons of the human brain. Its increased expression in basal ganglia neurons of patients with advanced HIV CNS disease suggests it may also contribute to pathogenesis.
AB - Recent in vitro studies suggest that the alpha chemokine stromal-derived factor-1α (SDF-1α) and its receptor CXCR-4 may contribute to neuronal apoptosis in HIV infection of the brain. The cellular and regional expression of this chemokine and its relationship to the AIDS dementia complex (ADC), however, have remained undetermined. Using immunohistochemistry and semiquantitative RT-PCR, we examined the expression of SDF-1α in the frontal cortex (FC), the adjacent deep white matter (DWM), and the basal ganglia (BG) of 17 patients with ADC and 5 normal controls, and the FC and temporal cortex of 6 patients with Alzheimer disease (AD). Additionally, SDF-1α expression was studied in 3 different neuronal cultures: differentiated SK-N-MC cells, primary human fetal neuronal, and mouse hippocampal cultures. SDF-1α staining was predominantly localized to astrocytes in all 3 groups in the gray matter of the FC and the BG, often in the vicinity of cortical and basal ganglia neurons, but was generally absent in the DWM. Further, the number of positive neurons was significantly greater in the BG of AIDS subjects with advanced brain disease compared to subjects with lesser disease (p = 0.029). All cultures showed prominent SDF-1α staining of neurons within the cytoplasm and in neurites, whereas preferential expression in GABA-ergic neurons was found in hippocampal cultures. This is the first study to show that SDF-1α is constitutively expressed in astrocytes of the deep and cortical gray matter as well as in neurons of the human brain. Its increased expression in basal ganglia neurons of patients with advanced HIV CNS disease suggests it may also contribute to pathogenesis.
KW - AIDS dementia complex
KW - Chemokines
KW - HIV
KW - Neurons
KW - SDF-1α
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U2 - 10.1093/jnen/62.6.617
DO - 10.1093/jnen/62.6.617
M3 - Article
C2 - 12834106
AN - SCOPUS:0038279766
SN - 0022-3069
VL - 62
SP - 617
EP - 626
JO - Journal of neuropathology and experimental neurology
JF - Journal of neuropathology and experimental neurology
IS - 6
ER -