Inhibition of tumor necrosis factor-alpha signaling prevents human immunodeficiency virus-1 protein Tat and methamphetamine interaction

Our previous studies demonstrated that the psychostimulant methamphetamine (MA) and the human immunodeficiency virus-1 (HIV-1) protein Tat interacted to cause enhanced dopaminergic neurotoxicity. The present study examined whether tumor necrosis factor-alpha (TNF-alpha) mediates the interaction between Tat and MA. In Sprague-Dawley rats, injections of Tat caused a small but significant increase in striatal TNF-alpha level, whereas MA resulted in no change. The increase in TNF-alpha induced by Tat + MA was not significantly different from that induced by Tat alone. Temporal analysis of TNF-alpha levels revealed a 50-fold increase 4 h after Tat administration. In C57BL/6 mice, Tat + MA induced a 50% decline in striatal dopamine levels, which was significantly attenuated in mice lacking both receptors for TNF-alpha. TNF-alpha synthesis inhibitors significantly attenuated Tat + MA neurotoxicity in hippocampal neuronal culture. The results suggest that Tat-induced elevation of TNF-alpha may predispose the dopaminergic terminals to subsequent damage by MA.

Medienart:

Artikel

Erscheinungsjahr:

2006

Erschienen:

2006

Enthalten in:

Zur Gesamtaufnahme - volume:23

Enthalten in:

Neurobiology of disease - 23(2006), 3 vom: 15. Sept., Seite 663-8

Sprache:

Englisch

Beteiligte Personen:

Theodore, Shaji [VerfasserIn]
Cass, Wayne A [VerfasserIn]
Nath, Avindra [VerfasserIn]
Steiner, Joseph [VerfasserIn]
Young, Kristie [VerfasserIn]
Maragos, William F [VerfasserIn]

Themen:

44RAL3456C
Dopamine
Dopamine Uptake Inhibitors
Gene Products, tat
Journal Article
Methamphetamine
Protein Synthesis Inhibitors
Research Support, N.I.H., Extramural
Tat Gene Products, Human Immunodeficiency Virus
Tumor Necrosis Factor-alpha
VTD58H1Z2X

Anmerkungen:

Date Completed 01.11.2006

Date Revised 21.11.2013

published: Print-Electronic

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM16401442X