Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598853 (forgetting)
 3,232 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats were given continuous intraventricular infusion of saline or the thiol-proteinase inhibitor leupeptin, via subcutaneously implanted osmotic minipumps, while being trained on a spatial learning water task using spaced trials. Leupeptin caused overnight forgetting during training, but performance eventually reached asymptote in both groups. A retention test conducted 48 h later to assess spatial memory revealed no significant group differences, but did cause, in saline-treated rats only, a disruption of subsequent retraining back to the correct spatial location. The groups showed no differences in Cl-dependent [3H]glutamate receptor binding to hippocampal or entorhinal cortex membranes subsequent to training. In a second experiment, normal rats trained on the same task also showed no differences in Cl-dependent [3H]glutamate binding relative to rats exposed to the water task but given random spatial position training and handled controls. The results are discussed in relation to the hypothesis of Lynch and Baudry (Science (1984) 224, 1057-1063) that a calcium-dependent thiol proteinase is involved in memory formation through its ability to modify glutamate receptor distribution and dendritic spine shape.
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PMID:Spatial learning in the rat: impairment induced by the thiol-proteinase inhibitor, leupeptin, and an analysis of [3H]glutamate receptor binding in relation to learning. 288 15

Long-term depression (LTD) of synaptic transmission, often used as an essential component in synaptic models for learning, memory and forgetting, can be produced in layer II/III of the visual cortex by a prolonged, low-frequency stimulation (LFS) of layer IV. The activation of Ca2+/calmodulin-dependent protein phosphatase, calcineurin, has been postulated to play a role in the induction of LTD. The recent introduction of a specific inhibitor for calcineurin, FK506, prompted the investigation of the involvement of this phosphatase in the induction of LTD in visual cortex. Thus, we administered FK506 at 1 microM to visual cortical slices of young rats, and found that it did not significantly affect field responses of layer II/III evoked by test stimulation of layer IV at 0.1 Hz, but prevented LTD of the responses from being induced by LFS (1 Hz for 15 min) in all the 10 slices tested. Without FK506, significant LTD was induced by the same parameters of LFS in 8 of the 12 slices. These results suggest the critical involvement of calcineurin in producing LTD in visual cortex.
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PMID:An inhibitor for calcineurin, FK506, blocks induction of long-term depression in rat visual cortex. 753 57

It has been demonstrated that long-term posttetanic heterosynaptic depression (LTHD), manifested in the form of a prolonged decrease in the probability of monosynaptic responses of the cell to stimulation of that afferent pathway which was not activated during conditioning tetanization of another input, takes place in the neocortex, as it does in the hippocampus. LTHD is characterized by such properties as its long-term character, cooperativity, and nonspecificity of input. LTHD in the nonconditioned input and long-term posttetanic potentiation or long-term posttetanic homosynaptic depression in the conditioned input may develop both in parallel or independantly of one another. It is hypothesized on the basis of the results obtained that LTHD (as is the case with LTP and LTD) is a calcium-dependant phenomenon, and that the achievement of a specific level of depolarization of the membrane in the region of the disposition of the inactive synapses is required for its occurrence. "Contrasting," i.e., a relative increase in the efficiency of transmission in the activating synapse, may be effected through LTHD; LTHD may be one of the mechanisms underlying forgetting.
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PMID:Neurobiology of the integrative activity of the brain: some properties of long-term posttetanic heterosynaptic depression in the motor cortex of the cat. 771 72

1. Long-term depression (LTD) is an activity-dependent reduction in the strength of synaptic transmission that can persist for hours. It is a neural model for processes underlying learning and memory, such as extinction and forgetting. LTD of excitatory postsynaptic potentials (EPSPs) in cells of the CA1 region of hippocampal slices can be induced in an anti-Hebbian paradigm, i.e., by conditioning stimuli that activate the postsynaptic neuron in the absence of evoked synaptic transmission in the test pathway. Past work showed that LTD was not produced consistently in a pharmacologically untreated slice, but it could be induced more reliably when the conditioning stimuli were applied during block of evoked transmitter release. We have now defined further the conditions in which LTD can be obtained using postsynaptic conditioning by investigating 1) whether intracellular conditioning is effective, 2) the requirement for extracellular Ca2+, and 3) the consequences of selective block of glutamate ionotropic receptor subtypes during the conditioning procedure. 2. Intracellular recordings were made from CA1 pyramidal neurons. Test shocks were applied to the stratum radiatum except during conditioning, and the depolarizing slopes and amplitudes of evoked EPSPs were measured. The conditioning procedure activated the postsynaptic neuron either antidromically (via trains of shocks at 100 Hz applied to the axons in the alveus) or intracellularly (via depolarizing pulses of 1.5-3.5 nA). During conditioning, postsynaptic potentials (PSPs) evoked by the conditioning stimuli either were transiently blocked by bathing slices for 5 min in artificial cerebrospinal fluid (CSF) containing a high [Mg2+] or were reduced by glutamate antagonists. 3. When slices were bathed in CSF containing 25 mM Mg2+ and 2 mM Ca2+, evoked PSPs were transiently abolished; conditioning, either by antidromic or intracellular stimulation, always evoked a significant LTD. During the LTD produced by antidromic stimulation, the mean EPSP slope was 52.6 +/- 11.4% (mean +/- SE) of its control at 30-35 min after conditioning (n = 7). The LTD produced by intracellular conditioning was of similar magnitude: the mean EPSP slope was 57.2 +/- 11.6% of its control at 30-35 min postconditioning (n = 7). When slices were bathed in CSF containing 25 mM Mg2+ and 2 mM Ca2+ without conditioning stimuli, there was no LTD (mean EPSP slope 109 +/- 8.1% of its control at 30-35 min after reperfusion with CSF; n = 5).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The postsynaptic induction of nonassociative long-term depression of excitatory synaptic transmission in rat hippocampal slices. 809 30

Renal lithiasis is a frequent disease which recurs in more than 60% of cases. Effective prevention of recurrence can be obtained once the cause has been identified. The laboratory investigation, based on clinical history, analysis of the stone and blood and urine assays, achieves this objective. As the stone is the main indicator of lithogenic disorders, the investigation must start by morphoconstitutional analysis of the stone by reliable physical methods. The results of this analysis guide the clinician towards the biochemical factors responsible for the lithogenic process and, in some cases, directly to certain infectious diseases, such as infections due to urease-positive bacteria, or metabolic diseases, such as primary hyperoxaluria, tubular acidosis or enzymatic deficits of purine metabolism, without forgetting drug causes, responsible for the formation of approximately one per cent of stones. Subsequent investigations guided by analysis of the stone are therefore much more selective and rational. When the stone is not available, the investigation, graduated according to the metabolic activity of the lithiasis, can be guided by its radiological appearance. Dynamic investigations are rarely necessary and must be reserved a second-line procedures for the most severe forms of calcium-dependent stones. In the absence of radiological data and when the stone has not been collected, a basic routine blood and urine investigation must be performed looking for laboratory factors potentially involved in the stone-forming process.
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PMID:[Metabolic assessment of urinary lithiasis in routine practice. Common task of nephrologists and urologists of the Lithiasis Committee of the French Association of Urology]. 923 85

The efficacy of excitatory synapses terminating on cortical and hippocampal pyramidal cells may be persistently depressed as well as potentiated. Homo-synaptic long-term depression (LTD) seems to be triggered by an entry of calcium into a post-synaptic cell less than that needed to initiate long-term potentiation (LTP). Theoretical work predicted, and experimental studies confirmed, that moderate elevations of calcium initiate LTD via a cascade of biochemical interactions involving calcium-dependent phosphatases. Genetically modified animals confirmed the prediction of a sliding threshold that defines the limit between LTD and LTP. While mechanisms for the initiation of LTD are quite well established, it remains unclear whether pre- or post-synaptic mechanisms, or both, are involved in its maintenance. A role for LTD in processes of learning and forgetting in the adult animal remains to be firmly established. It seems probable, however, that a persistent reduction in synaptic weight is a basic process used in the establishment and refinement of neuronal circuits during development.
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PMID:[Long-term depression of excitatory synapses in the cortex and hippocampus]. 975 29

Anatomical change in the anatomy of the gastrointestinal tract after bariatric surgery leads to modification of dietary patterns that have to be adapted to new physiological conditions, either related with the volume of intakes or the characteristics of the macro- and micronutrients to be administered. Restrictive diet after bariatric surgery (basically gastric bypass and restrictive procedures) is done at several steps. The first phase after surgery consists in the administration of clear liquids for 2-3 days, followed by completely low-fat and high-protein content (> 50-60 g/day) liquid diet for 2-4 weeks, normally by means of formula-diets. Soft or grinded diet including very soft protein-rich foods, such as egg, low-calories cheese, and lean meats such as chicken, cow, pork, or fish (red meats are not so well tolerated) is recommended 2-4 weeks after hospital discharge. Normal diet may be started within 8 weeks from surgery or even later. It is important to incorporate hyperproteic foods with each meal, such egg whites, lean meats, cheese or milk. All these indications should be done under the supervision of an expert nutrition professional to always advise the patients and adapting the diet to some special situations (nausea/vomiting, constipation, diarrhea, dumping syndrome, dehydration, food intolerances, overfeeding, etc.). The most frequent vitamin and mineral deficiencies in the different types of surgeries are reviewed, with a special focus on iron, vitamin B12, calcium, and vitamin D metabolism. It should not be forgotten that the aim of obesity surgery is making the patient loose weight and thus post-surgery diet is designed to achieve that goal although without forgetting the essential role that nutritional education has on the learning of new dietary habits contributing to maintain that weight loss over time.
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PMID:[Nutritional implications of bariatric surgery on the gastrointestinal tract]. 1767

The paper reviews the existing and future nootropic drugs (cognition enhancers) with different mechanisms of action and heterogenous chemical structures, which have been developed on the basis of knowledge of the mechanisms of learning, memory and forgetting, as well as degenerative processes in aging brain and disease-associated cognitive impairments. These agents influence on acetylcholine-, glutamate-, GABA-, 5-HT-, dopamine-, histamine-, adenosine-, phosphodiesterase-, neurotrophic- systems, and neurohormones. Neuropeptides and their analogs, blood flow enhancers, calcium-channel blockers, antioxidants and vitamins and herbal preparations, and some other agents improving cerebral metabolism and influencing the neurodegeneracy involved in Alzheimer's disease are considered. An original classification of cognition enhancers, based on mechanisms of their action, includes more than 200 drugs in current use and those currently under development.
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PMID:[Nootropes (cognition enhancers) and neuroprotectors]. 1807 43

Calcium/calmodulin-dependent kinases (CaM-kinases) are central to various forms of long-term memory (LTM) in a number of evolutionarily diverse organisms. However, it is still largely unknown what contributions specific CaM-kinases make to different phases of the same specific type of memory, such as acquisition, or early, intermediate, and late consolidation of associative LTM after classical conditioning. Here, we investigated the involvement of CaM-kinase II (CaMKII) in different phases of associative LTM induced by single-trial reward classical conditioning in Lymnaea, a well established invertebrate experimental system for studying molecular mechanisms of learning and memory. First, by using a general CaM-kinase inhibitor, KN-62, we found that CaM-kinase activation was necessary for acquisition and late consolidation, but not early or intermediate consolidation or retrieval of LTM. Then, we used Western blot-based phosphorylation assays and treatment with CaMKIINtide to identify CaMKII as the main CaM-kinase, the intrinsic activation of which, in a critical time window ( approximately 24 h after learning), is central to late consolidation of LTM. Additionally, using MK-801 and CaMKIINtide we found that acquisition was dependent on both NMDA receptor and CaMKII activation. However, unlike acquisition, CaMKII-dependent late memory consolidation does not require the activation of NMDA receptors. Our new findings support the notion that even apparently stable memory traces may undergo further molecular changes and identify NMDA-independent intrinsic activation of CaMKII as a mechanism underlying this "lingering consolidation." This process may facilitate the preservation of LTM in the face of protein turnover or active molecular processes that underlie forgetting.
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PMID:Delayed intrinsic activation of an NMDA-independent CaM-kinase II in a critical time window is necessary for late consolidation of an associative memory. 2005 87

Forgetting may allow an animal to react more appropriately to current conditions, rather than continuing to exhibit a previously learned, possibly maladaptive behaviour based on previous experience. One theory is that forgetting is an active process, whereby the previously learnt response is replaced by new learning that interferes with the older memory. Hence, we hypothesized that an appropriately timed environmental stressor that blocks long-term memory (LTM) formation would also block forgetting. Lymnaea stagnalis (L.) is a freshwater snail, which requires environmental calcium of at least 20 mg l(-1) to meet its requirements. Low environmental Ca(2+) (i.e. 20 mg l(-1)) in their environment acts as a stressor, and prevents LTM formation. Here, we asked whether a low Ca(2+) environment would also prevent forgetting, concordant with the retrograde interference model of Jenkins and Dallenbach. Snails were operantly conditioned to reduce aerial respiration in hypoxia. When maintained in standard conditions (80 mg l(-1) Ca(2+)), snails demonstrated LTM following training lasting 24 h, but not 72 h; however, when trained in standard conditions then exposed to a low Ca(2+) environment (20 mg l(-1)) immediately following training, they retained memory for at least 96 h, indicating that forgetting had been blocked. Thus, when exposed to low environmental Ca(2+), Lymnaea will fail to form new memories, but will also continue to retain information previously learned and remembered as the low calcium blocks forgetting.
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PMID:Low external environmental calcium levels prevent forgetting in Lymnaea. 2161 29


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