Increased vulnerability of ApoE4 neurons to HIV proteins and opiates: Protection by diosgenin and l-deprenyl

Jadwiga Turchan-Cholewo; Yiling Liu; Suzanne Gartner; Rollie Reid; Chunfa Jie; Xuejun Peng; Kuey Chu C. Chen; Ashok Chauhan; Norman Haughey; Roy Cutler; Mark P. Mattson; Carlos Pardo; Katherine Conant; Ned Sacktor; Justin C. McArthur; Kurt F. Hauser; Chandra Gairola; Avindra Nath

Neurobiology of Disease (Jul 2006)

Increased vulnerability of ApoE4 neurons to HIV proteins and opiates: Protection by diosgenin and l-deprenyl

Jadwiga Turchan-Cholewo,
Yiling Liu,
Suzanne Gartner,
Rollie Reid,
Chunfa Jie,
Xuejun Peng,
Kuey Chu C. Chen,
Ashok Chauhan,
Norman Haughey,
Roy Cutler,
Mark P. Mattson,
Carlos Pardo,
Katherine Conant,
Ned Sacktor,
Justin C. McArthur,
Kurt F. Hauser,
Chandra Gairola,
Avindra Nath

Affiliations

Jadwiga Turchan-Cholewo: Departments of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40546, USA
Yiling Liu: Department of Neurology, Johns Hopkins University, 600 N. Wolfe Street, 509 Pathology, Baltimore, MD 21287, USA
Suzanne Gartner: Department of Neurology, Johns Hopkins University, 600 N. Wolfe Street, 509 Pathology, Baltimore, MD 21287, USA
Rollie Reid: Department of Neurology, Johns Hopkins University, 600 N. Wolfe Street, 509 Pathology, Baltimore, MD 21287, USA
Chunfa Jie: Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21287, USA
Xuejun Peng: Microarray core, University of Kentucky, Lexington, KY 40546, USA
Kuey Chu C. Chen: Microarray core, University of Kentucky, Lexington, KY 40546, USA
Ashok Chauhan: Department of Neurology, Johns Hopkins University, 600 N. Wolfe Street, 509 Pathology, Baltimore, MD 21287, USA
Norman Haughey: Department of Neurology, Johns Hopkins University, 600 N. Wolfe Street, 509 Pathology, Baltimore, MD 21287, USA
Roy Cutler: National Institute of Aging, Baltimore, MD 20892, USA
Mark P. Mattson: National Institute of Aging, Baltimore, MD 20892, USA
Carlos Pardo: Department of Neurology, Johns Hopkins University, 600 N. Wolfe Street, 509 Pathology, Baltimore, MD 21287, USA
Katherine Conant: Department of Neurology, Johns Hopkins University, 600 N. Wolfe Street, 509 Pathology, Baltimore, MD 21287, USA
Ned Sacktor: Department of Neurology, Johns Hopkins University, 600 N. Wolfe Street, 509 Pathology, Baltimore, MD 21287, USA
Justin C. McArthur: Department of Neurology, Johns Hopkins University, 600 N. Wolfe Street, 509 Pathology, Baltimore, MD 21287, USA
Kurt F. Hauser: Departments of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40546, USA
Chandra Gairola: Department of Pharmacy, University of Kentucky, Lexington, KY 40546, USA
Avindra Nath: Department of Neurology, Johns Hopkins University, 600 N. Wolfe Street, 509 Pathology, Baltimore, MD 21287, USA; Corresponding author. Fax: +1 410 502 8075.

Journal volume & issue: Vol. 23, no. 1
pp. 109 – 119

Abstract

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Human immunodeficiency virus (HIV) infection continues to rise in drug-abusing populations and causes a dementing illness in a subset of individuals. Factors contributing to the development of dementia in this population remain unknown. We found that HIV-infected individuals with the E4 allele of Apolipoprotein E (ApoE) or history of intravenous drug abuse had increased oxidative stress in the CNS. In vitro studies showed that HIV proteins, gp120 and Tat, Tat + morphine but not tumor necrosis factor-α (TNF-α), caused increased neurotoxicity in human neuronal cultures with ApoE4 allele. Microarray analysis showed a differential alteration of transcripts involved in energy metabolism in cultures of ApoE3 and 4 neurons upon treatment with Tat + morphine. This was confirmed using assays of mitochondrial function and exposure of the neurons to Tat + morphine. Using this in vitro model, we screened a number of novel antioxidants and found that only l-deprenyl and diosgenin protected against the neurotoxicity of Tat + morphine. Furthermore, Tat-induced oxidative stress impaired morphine metabolism which could also be prevented by diosgenin. In conclusion, opiate abusers with HIV infection and the ApoE4 allele may be at increased risk of developing dementia. l-deprenyl and a plant estrogen, diosgenin, may have therapeutic potential in this population.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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