Decreased glial and synaptic glutamate uptake in the striatum of HIV-1 gp120 transgenic mice
In: Journal of neurovirology, Jg. 22 (2015-05-08), Heft 3
Online
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Zugriff:
The mechanisms leading to the neurocognitive deficits in humans with immunodeficiency virus type 1 (HIV-1) are not well resolved. A number of cell culture models have demonstrated that the HIV-envelope glycoprotein 120 (gp120) decreases the reuptake of glutamate, which is necessary for learning, memory, and synaptic plasticity. However, the impact of brain HIV-1 gp120 on glutamate uptake systems in vivo remains unknown. Notably, alterations in brain glutamate uptake systems are implicated in a number of neurodegenerative and neurocognitive disorders. We characterized the kinetic properties of system XAG (sodium-dependent) and systems xc- (sodium-independent) [3H]-L-glutamate uptake in the striatum and hippocampus of HIV-1 gp120 transgenic mice, an established model of HIV neuropathology. We determined the kinetic constant Vmax (maximal velocity) and Km (affinity) of both systems XAG and xc- using subcellular preparations derived from neurons and glial cells. We show significant (30-35 %) reductions in the Vmax of systems XAG and xc- in both neuronal and glial preparations derived from the striatum, but not from the hippocampus of gp120 mice relative to wild-type (WT) controls. Moreover, immunoblot analysis showed that the protein expression of glutamate transporter subtype-1 (GLT-1), the predominant brain glutamate transporter, was significantly reduced in the striatum but not in the hippocampus of gp120 mice. These extensive and region-specific deficits of glutamate uptake likely contribute to the development and/or severity of HIV-associated neurocognitive disorders. Understanding the role of striatal glutamate uptake systems in HIV-1 gp120 may advance the development of new therapeutic strategies to prevent neuronal damage and improve cognitive function in HIV patients.
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Decreased glial and synaptic glutamate uptake in the striatum of HIV-1 gp120 transgenic mice
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Autor/in / Beteiligte Person: | Lasalde-Dominicci, José A. ; Capó-Vélez, Coral M. ; Roman, Cristina ; Melendez, Roberto I. |
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Zeitschrift: | Journal of neurovirology, Jg. 22 (2015-05-08), Heft 3 |
Veröffentlichung: | 2015 |
Medientyp: | unknown |
ISSN: | 1538-2443 (print) |
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