SDF-1α is expressed in astrocytes and neurons in the AIDS dementia complex

An in vivo and in vitro study

Kevin Rostasy, Christophe Egles, Ashok Chauhan, Michelle Kneissl, Padmanabhan Bahrani, Constantin Yiannoutsos, Dale D. Hunter, Avindra Nath, John C. Hedreen, Bradford A. Navia

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)617-626
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume62
Issue number6
StatePublished - Jun 1 2003

Fingerprint

AIDS Dementia Complex
Basal Ganglia
Astrocytes
Neurons
Frontal Lobe
CXCR Receptors
Staining and Labeling
CXC Chemokines
GABAergic Neurons
Central Nervous System Diseases
Brain
Brain Diseases
Neurites
Temporal Lobe
Chemokines
HIV Infections
Alzheimer Disease
Cytoplasm
Acquired Immunodeficiency Syndrome
Immunohistochemistry

Keywords

  • AIDS dementia complex
  • Chemokines
  • HIV
  • Neurons
  • SDF-1α

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

SDF-1α is expressed in astrocytes and neurons in the AIDS dementia complex : An in vivo and in vitro study. / Rostasy, Kevin; Egles, Christophe; Chauhan, Ashok; Kneissl, Michelle; Bahrani, Padmanabhan; Yiannoutsos, Constantin; Hunter, Dale D.; Nath, Avindra; Hedreen, John C.; Navia, Bradford A.

In: Journal of Neuropathology and Experimental Neurology, Vol. 62, No. 6, 01.06.2003, p. 617-626.

Research output: Contribution to journalArticle

Rostasy, K, Egles, C, Chauhan, A, Kneissl, M, Bahrani, P, Yiannoutsos, C, Hunter, DD, Nath, A, Hedreen, JC & Navia, BA 2003, 'SDF-1α is expressed in astrocytes and neurons in the AIDS dementia complex: An in vivo and in vitro study', Journal of Neuropathology and Experimental Neurology, vol. 62, no. 6, pp. 617-626.
Rostasy, Kevin ; Egles, Christophe ; Chauhan, Ashok ; Kneissl, Michelle ; Bahrani, Padmanabhan ; Yiannoutsos, Constantin ; Hunter, Dale D. ; Nath, Avindra ; Hedreen, John C. ; Navia, Bradford A. / SDF-1α is expressed in astrocytes and neurons in the AIDS dementia complex : An in vivo and in vitro study. In: Journal of Neuropathology and Experimental Neurology. 2003 ; Vol. 62, No. 6. pp. 617-626.
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