Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002622 (amnesia)
 5,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been demonstrated that a gradual spontaneous recovery of a previously unreproducible memory trace and the prevention of the antiamnesic effect of the blockade of the GABAA receptor, but not of the blockade of the benzodiazepine receptor or the chloride channel, take place with the development of amnesia against the background of the activation of the GABAB receptor by baclofen. The "neurochemical set" created by the activation of the GABAA receptor by muscimol in a dose of 1 mg/kg prevents the antiamnesic effect of the blockade of any component of the benzodiazepine-GABA-ionophore complex, while at a dose of muscimol of 0.5 mg/kg, the retrieval of the amnestic trace takes place only by blockade of the benzodiazepine receptor. Thus, the development of amnesia is determined by the functional state of inhibitory GABAergic systems of the brain, which governs the subsequent correction of the amnestic memory trace.
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PMID:The role of GABAA and GABAB receptors in the development of amnesia. 217 29

The paper deals with analysis of the influence of blockade of separate components of benzodiazepine-GABA-ionophore complex on the recovery of memory trace amnesia under GABA-A and GABA-B receptors activation in the experiments with conditioned reaction of passive avoidance of mice. Activation of GABA-A receptors did not change the behavioural amnesia manifestation at all terms of testing. Activation of GABA-B receptors before learning and amnestic influence caused spontaneous recovery of avoidance reaction. Blockade of chloride channel by picrotoxin and of benzodiazepine receptor by flumazepil restored the reproduction of the memory trace disturbed against the background of GABA-B receptors activation. Systemic flumazepil administration contributed to the memory trace reproduction against the background of GABA-A receptors activation by muscimol in the dose of 0.5 mg/kg. In conditions of amnesia development against the background of muscimol in the dose of 1 mg/kg the blockade of any component of benzodiazepine-GABA-ionophore complex was not effective. The obtained data testify that activation of GABA-A and GABA-B receptors changes the amnesia development and correction of amnesia memory trace by the blockade of separate components of benzodiazepine-GABA-ionophore complex.
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PMID:[The role of GABA-A and GABA-B receptors in the development of amnesia]. 255 16

Dehydroepiandrosterone sulfate (DHEAS) is a neurosteroid which functions as a negative allosteric modulator of the GABA(A) receptor-gated chloride channel. Steroid sulfatase inhibitors including (p-O-sulfamoyl)-N-tetradecanoyl tyramine (DU-14), can potentiate the blockade of the amnestic effects of scopolamine by exogenously administered DHEAS. Moreover, when administered over a 15 day period, DU-14 can block scopolamine amnesia without the concurrent administration of DHEAS. Since the enzyme, steroid sulfatase, facilitates the hydrolysis of the sulfate moiety from DHEAS, the intent of this study was to determine whether chronic administration of DU-14 could increase whole brain concentrations of endogenous DHEAS. Rats were administered DU-14 or corn oil vehicle for 15 days. Following the last day the animals were sacrificed and the brains were removed and analyzed for DHEAS content. DU-14 increased the whole brain concentration of DHEAS 77.6%, from 0.65 +/- 0.06 to 1.15 +/- 0.12 microg/g (mean +/- SEM). This result suggests that steroid sulfatase inhibitors may enhance cognitive function following chronic treatment by increasing the concentration of excitatory neurosteroids such as DHEAS in the brain. Steroid sulfatase inhibitors, therefore, may provide a novel mechanism for facilitating central nervous system function.
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PMID:Chronic steroid sulfatase inhibition by (p-O-sulfamoyl)-N-tetradecanoyl tyramine increases dehydroepiandrosterone sulfate in whole brain. 939 36

Gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian Central Nervous System (CNS). GABA participates in the regulation of neuronal excitability through interaction with specific membrane proteins (the GABAA receptors). The binding of GABA to these postsynaptic receptors, results in an opening of a chloride channel integrated in the receptor which allows the entry of Cl- and consequently leads to hyperpolarization of the recipient cell. The action of GABA is allosterically modulated by a wide variety of chemical entities which interact with distinct binding sites at the GABAA receptor complex. One of the most thoroughly investigated modulatory site is the benzodiazepine binding site. The benzodiazepines constitute a well-known class of therapeutics displaying hypnotic, anxiolytic and anticonvulsant effects. Their usefulness, however, is limited by a broad range of side effects comprising sedation, ataxia, amnesia, alcohol and barbiturate potentiation, tolerance development and abuse potential. Consequently, there has been an intensive search for modulatory agents with an improved profile, and a diversity of chemical entities distinct from the benzodiazepines, but with GABA modulatory effects have been identified. The existence of endogenous ligands for the GABAA receptor complex beside GABA has often been described, but their role in the regulation of GABA action is still a matter of controversy. The progress of molecular biology during the last decade has contributed enormously to the understanding of benzodiazepine receptor pharmacology. A total of 14 GABAA receptor subunits have been cloned from mammalian brain and have been expressed/co-expressed in stable cell lines. These transfected cells constitute an important tool in the characterization of subtype selective ligands. In spite of the rapidly expanding knowledge of the molecular and pharmacological mechanisms involved in GABA/benzodiazepine related CNS disorders, the identification of clinically selective acting drugs is still to come.
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PMID:Ligands for the benzodiazepine binding site--a survey. 1021 98

Enhancing inhibition via gamma-aminobutyric acid type A (GABA(A)) receptors contributes to anesthetic-induced impairment of long-term potentiation (LTP) of excitatory synaptic transmission, which may account for general anesthesia-associated memory impairment (amnesia). The neuron-specific K+ -Cl- cotransporter 2 (KCC2) is necessary for fast synaptic inhibition via maintaining the low intracellular chloride concentration required for the hyperpolarizing actions of GABA via GABA(A) receptors. To explore a possible role of KCC2-dependent inhibition in anesthetic-induced impairment of LTP, we used field excitatory postsynaptic potentials (fEPSP) recording and immunoblotting to study the effect of propofol on LTP maintenance and KCC2 expression in CA1 region of rat hippocampal slices. We found that propofol (30 microM) not only impaired LTP expression but also prevented LTP-accompanied downregulation of KCC2 without affecting the basal transmission of glutamatergic synapses. Moreover, the recurrent inhibition in hippocampal slices was enhanced by propofol. These propofol-induced effects were completely abolished by picrotoxin, a specific GABA(A) receptor-chloride channel blocker. Thus, enhancement of GABAergic inhibition and suppression of neuronal excitability may account for the sustained expression of KCC2 and the impairment of LTP by propofol. Together, this study supports a novel role for KCC2 in LTP expression and gives hints to a molecular mechanism, by which anesthetics might cause impairment of LTP.
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PMID:Changes of K+ -Cl- cotransporter 2 (KCC2) and circuit activity in propofol-induced impairment of long-term potentiation in rat hippocampal slices. 1702 80