HIV-1 protein gp120 rapidly impairs memory in chicks by interrupting the glutamate-glutamine cycle

Samantha Paubrey Fernandes, Thomas Mark Edwards, Kim Tee Ng, Stephen Richard Robinson

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Abstract Learning and memory impairments are frequently observed in patients suffering from AIDS Dementia Complex (ADC). These effects have been linked to the presence of gp120, an HIV viral coat glycoprotein. The present study investigated the possibility that gp120 prevents the uptake of extracellular glutamate by astrocytes, leading to an interruption of the glutamate?glutamine cycle and a subsequent impairment of memory. Ten microliters of 10 nM gp120 was bilaterally injected into the region of the intermediate medial mesopallium of day-old chicks at various times before, or after, training using a single-trial passive avoidance task. Gp120 was found to significantly impair memory retention when injected 10?40 min after training. Memory impairments were evident within 5 min of gp120 administration and remained evident 24 h later. Further, the amnestic effect of gp120 could be overcome with glutamine or with precursors of glutamate synthesis, but only weakly by glutamate. These results support the conclusion that the amnestic effect of gp120 is due to an impaired uptake of glutamate by astrocytes and a subsequent interruption of glutamine supply to neurones. The data indicate that the glutamate?glutamine cycle may be a useful therapeutic target in the treatment of ADC.
Original languageEnglish
Pages (from-to)1 - 8
Number of pages8
JournalNeurobiology of Learning and Memory
Volume87
Issue number1
DOIs
Publication statusPublished - 2007

Cite this

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title = "HIV-1 protein gp120 rapidly impairs memory in chicks by interrupting the glutamate-glutamine cycle",
abstract = "Abstract Learning and memory impairments are frequently observed in patients suffering from AIDS Dementia Complex (ADC). These effects have been linked to the presence of gp120, an HIV viral coat glycoprotein. The present study investigated the possibility that gp120 prevents the uptake of extracellular glutamate by astrocytes, leading to an interruption of the glutamate?glutamine cycle and a subsequent impairment of memory. Ten microliters of 10 nM gp120 was bilaterally injected into the region of the intermediate medial mesopallium of day-old chicks at various times before, or after, training using a single-trial passive avoidance task. Gp120 was found to significantly impair memory retention when injected 10?40 min after training. Memory impairments were evident within 5 min of gp120 administration and remained evident 24 h later. Further, the amnestic effect of gp120 could be overcome with glutamine or with precursors of glutamate synthesis, but only weakly by glutamate. These results support the conclusion that the amnestic effect of gp120 is due to an impaired uptake of glutamate by astrocytes and a subsequent interruption of glutamine supply to neurones. The data indicate that the glutamate?glutamine cycle may be a useful therapeutic target in the treatment of ADC.",
author = "Fernandes, {Samantha Paubrey} and Edwards, {Thomas Mark} and Ng, {Kim Tee} and Robinson, {Stephen Richard}",
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HIV-1 protein gp120 rapidly impairs memory in chicks by interrupting the glutamate-glutamine cycle. / Fernandes, Samantha Paubrey; Edwards, Thomas Mark; Ng, Kim Tee; Robinson, Stephen Richard.

In: Neurobiology of Learning and Memory, Vol. 87, No. 1, 2007, p. 1 - 8.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - HIV-1 protein gp120 rapidly impairs memory in chicks by interrupting the glutamate-glutamine cycle

AU - Fernandes, Samantha Paubrey

AU - Edwards, Thomas Mark

AU - Ng, Kim Tee

AU - Robinson, Stephen Richard

PY - 2007

Y1 - 2007

N2 - Abstract Learning and memory impairments are frequently observed in patients suffering from AIDS Dementia Complex (ADC). These effects have been linked to the presence of gp120, an HIV viral coat glycoprotein. The present study investigated the possibility that gp120 prevents the uptake of extracellular glutamate by astrocytes, leading to an interruption of the glutamate?glutamine cycle and a subsequent impairment of memory. Ten microliters of 10 nM gp120 was bilaterally injected into the region of the intermediate medial mesopallium of day-old chicks at various times before, or after, training using a single-trial passive avoidance task. Gp120 was found to significantly impair memory retention when injected 10?40 min after training. Memory impairments were evident within 5 min of gp120 administration and remained evident 24 h later. Further, the amnestic effect of gp120 could be overcome with glutamine or with precursors of glutamate synthesis, but only weakly by glutamate. These results support the conclusion that the amnestic effect of gp120 is due to an impaired uptake of glutamate by astrocytes and a subsequent interruption of glutamine supply to neurones. The data indicate that the glutamate?glutamine cycle may be a useful therapeutic target in the treatment of ADC.

AB - Abstract Learning and memory impairments are frequently observed in patients suffering from AIDS Dementia Complex (ADC). These effects have been linked to the presence of gp120, an HIV viral coat glycoprotein. The present study investigated the possibility that gp120 prevents the uptake of extracellular glutamate by astrocytes, leading to an interruption of the glutamate?glutamine cycle and a subsequent impairment of memory. Ten microliters of 10 nM gp120 was bilaterally injected into the region of the intermediate medial mesopallium of day-old chicks at various times before, or after, training using a single-trial passive avoidance task. Gp120 was found to significantly impair memory retention when injected 10?40 min after training. Memory impairments were evident within 5 min of gp120 administration and remained evident 24 h later. Further, the amnestic effect of gp120 could be overcome with glutamine or with precursors of glutamate synthesis, but only weakly by glutamate. These results support the conclusion that the amnestic effect of gp120 is due to an impaired uptake of glutamate by astrocytes and a subsequent interruption of glutamine supply to neurones. The data indicate that the glutamate?glutamine cycle may be a useful therapeutic target in the treatment of ADC.

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