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HIV-1 gp120 neurotoxicity proximally and at a distance from the point of exposure: protection by rSV40 delivery of antioxidant enzymes.
Neurobiol Dis. 2009 Jun; 34(3):462-76.ND

Abstract

Toxicity of HIV-1 envelope glycoprotein (gp120) for substantia nigra (SN) neurons may contribute to the Parkinsonian manifestations often seen in HIV-1-associated dementia (HAD). We studied the neurotoxicity of gp120 for dopaminergic neurons and potential neuroprotection by antioxidant gene delivery. Rats were injected stereotaxically into their caudate-putamen (CP); CP and (substantia nigra) SN neuron loss was quantified. The area of neuron loss extended several millimeters from the injection site, approximately 35% of the CP area. SN neurons, outside of this area of direct neurotoxicity, were also severely affected. Dopaminergic SN neurons (expressing tyrosine hydroxylase, TH, in the SN and dopamine transporter, DAT, in the CP) were mostly affected: intra-CP gp120 caused approximately 50% DAT+ SN neuron loss. Prior intra-CP gene delivery of Cu/Zn superoxide dismutase (SOD1) or glutathione peroxidase (GPx1) protected SN neurons from intra-CP gp120. Thus, SN dopaminergic neurons are highly sensitive to HIV-1 gp120-induced neurotoxicity, and antioxidant gene delivery, even at a distance, is protective.

Authors+Show Affiliations

Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. jplouboutin@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19327399

Citation

Louboutin, Jean-Pierre, et al. "HIV-1 Gp120 Neurotoxicity Proximally and at a Distance From the Point of Exposure: Protection By rSV40 Delivery of Antioxidant Enzymes." Neurobiology of Disease, vol. 34, no. 3, 2009, pp. 462-76.
Louboutin JP, Agrawal L, Reyes BA, et al. HIV-1 gp120 neurotoxicity proximally and at a distance from the point of exposure: protection by rSV40 delivery of antioxidant enzymes. Neurobiol Dis. 2009;34(3):462-76.
Louboutin, J. P., Agrawal, L., Reyes, B. A., Van Bockstaele, E. J., & Strayer, D. S. (2009). HIV-1 gp120 neurotoxicity proximally and at a distance from the point of exposure: protection by rSV40 delivery of antioxidant enzymes. Neurobiology of Disease, 34(3), 462-76. https://doi.org/10.1016/j.nbd.2009.03.003
Louboutin JP, et al. HIV-1 Gp120 Neurotoxicity Proximally and at a Distance From the Point of Exposure: Protection By rSV40 Delivery of Antioxidant Enzymes. Neurobiol Dis. 2009;34(3):462-76. PubMed PMID: 19327399.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HIV-1 gp120 neurotoxicity proximally and at a distance from the point of exposure: protection by rSV40 delivery of antioxidant enzymes. AU - Louboutin,Jean-Pierre, AU - Agrawal,Lokesh, AU - Reyes,Beverly A S, AU - Van Bockstaele,Elisabeth J, AU - Strayer,David S, Y1 - 2009/03/25/ PY - 2008/10/26/received PY - 2009/02/26/revised PY - 2009/03/04/accepted PY - 2009/3/31/entrez PY - 2009/3/31/pubmed PY - 2009/8/18/medline SP - 462 EP - 76 JF - Neurobiology of disease JO - Neurobiol Dis VL - 34 IS - 3 N2 - Toxicity of HIV-1 envelope glycoprotein (gp120) for substantia nigra (SN) neurons may contribute to the Parkinsonian manifestations often seen in HIV-1-associated dementia (HAD). We studied the neurotoxicity of gp120 for dopaminergic neurons and potential neuroprotection by antioxidant gene delivery. Rats were injected stereotaxically into their caudate-putamen (CP); CP and (substantia nigra) SN neuron loss was quantified. The area of neuron loss extended several millimeters from the injection site, approximately 35% of the CP area. SN neurons, outside of this area of direct neurotoxicity, were also severely affected. Dopaminergic SN neurons (expressing tyrosine hydroxylase, TH, in the SN and dopamine transporter, DAT, in the CP) were mostly affected: intra-CP gp120 caused approximately 50% DAT+ SN neuron loss. Prior intra-CP gene delivery of Cu/Zn superoxide dismutase (SOD1) or glutathione peroxidase (GPx1) protected SN neurons from intra-CP gp120. Thus, SN dopaminergic neurons are highly sensitive to HIV-1 gp120-induced neurotoxicity, and antioxidant gene delivery, even at a distance, is protective. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/19327399/HIV_1_gp120_neurotoxicity_proximally_and_at_a_distance_from_the_point_of_exposure:_protection_by_rSV40_delivery_of_antioxidant_enzymes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(09)00055-2 DB - PRIME DP - Unbound Medicine ER -