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Antisense Oligonucleotide to GABAA Receptor Gamma 2 Subunit Induces Loss of Neurones in Rat Hippocampus

Antisense Oligonucleotide to GABAA Receptor Gamma 2 Subunit Induces Loss of Neurones in Rat Hippocampus

J Karle, M R Witt, M Nielsen

Neurosci Lett. 1995 Dec 29;202(1-2):97-100.

PMID: 8787840

Abstract:

The binding site for 1,4-benzodiazepines in the brain is part of the hetero-oligomeric gamma-aminobutyric acid (GABA)A receptor complex which regulates a chloride ion channel. The presence of the gamma 2 subunit in the complex is necessary for the binding of benzodiazepines to their binding site. This study demonstrates a reduction of benzodiazepine receptor radioligand binding by 43% compared to control following infusion of phosphorothioate antisense oligodeoxynucleotide to gamma 2 subunit into rat hippocampus. Reduction of benzodiazepine binding sites was paralleled by a decrease in [35S]tert-butyl-bicyclo-phosphorothionate ([35S]TBPS) binding (51%) and [3H]muscimol binding (37%), indicating a reduction in the number of GABAA receptors. Changed macroscopic appearance, reduced protein content and severe loss of neurones in antisense-treated hippocampi suggests that the reduced formation of GABAA receptors leads to neuronal cell death.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP70636861	tert-Butyl bicyclo[2.2.2]phosphorothionate		70636-86-1	Price

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