SDF-1alpha is expressed in astrocytes and neurons in the AIDS dementia complex: an in vivo and in vitro study.
Recent in vitro studies suggest that the alpha chemokine stromal-derived factor-1alpha (SDF-1alpha) 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-1alpha 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-1alpha expression was studied in 3 different neuronal cultures: differentiated SK-N-MC cells, primary human fetal neuronal, and mouse hippocampal cultures. SDF-1alpha 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-1alpha 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-1alpha 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.
Rostasy
Kevin
K
Pediatric Neurology, University of Goettingen, Germany.
Egles
Christophe
C
Chauhan
Ashok
A
Kneissl
Michelle
M
Bahrani
Padmanabhan
P
Yiannoutsos
Constantin
C
Hunter
Dale D
DD
Nath
Avindra
A
Hedreen
John C
JC
Navia
Bradford A
BA
D015526:AIDS Dementia Complex / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015152:Blotting, Northern / Q000379:methods; D015139:Blotting, Southern / Q000379:methods; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured / Q000821:virology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D005333:Fetus; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation; D015696:Gene Products, tat / Q000378:metabolism; D006678:HIV / Q000472:pathogenicity; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D006573:Heterocyclic Compounds, 1-Ring / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D051379:Mice; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D015696:Gene Products, tat; D015699:HIV Envelope Protein gp120; D006573:Heterocyclic Compounds, 1-Ring; D012333:RNA, Messenger; D011994:Recombinant Proteins; C411322:Tat-DOTA; D014409:Tumor Necrosis Factor-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus; D005680:gamma-Aminobutyric Acid