Short-term Memory Enhancement Research Articles

The Lysine Acetyltransferase PCAF Functionally Interacts with Estrogen Receptor Alpha in the Hippocampus of Gonadally Intact Male-But Not Female-Rats to Enhance Short-Term Memory.

Acetylation of histone proteins by histone acetyltransferases (HATs), and the resultant change in gene expression, is a well-established mechanism necessary for long-term memory (LTM) consolidation, which is not required for short-term memory (STM). However, we previously demonstrated that the HAT p300/CBP-associated factor (PCAF) also influences hippocampus (HPC)-dependent STM in male rats. In addition to their epigenetic activity, HATs acetylate nonhistone proteins involved in nongenomic cellular processes, such as estrogen receptors (ERs). Given that ERs have rapid, nongenomic effects on HPC-dependent STM, we investigated the potential interaction between ERs and PCAF for STM mediated by the dorsal hippocampus (dHPC). Using a series of pharmacological agents administered directly into the dHPC, we reveal a functional interaction between PCAF and ERα in the facilitation of short-term object-in-place memory in male but not female rats. This interaction was specific to ERα, while ERβ agonism did not enhance STM. It was further specific to dHPC STM, as the effect was not present in the dHPC for LTM or in the perirhinal cortex. Further, while STM required local (i.e., dHPC) estrogen synthesis, the facilitatory interaction effect appeared independent of estrogens. Finally, western blot analyses demonstrated that PCAF activation in the dHPC rapidly (5 min) activated downstream estrogen-related cell signaling kinases (c-Jun N-terminal kinase and extracellular signal-related kinase). Collectively, these findings indicate that PCAF, which is typically implicated in LTM through epigenetic processes, also influences STM in the dHPC, possibly via nongenomic ER activity. Critically, this novel PCAF-ER interaction might exist as a male-specific mechanism supporting STM.

HHSKT: A learner–question interactions based heterogeneous graph neural network model for knowledge tracing

Knowledge tracing (KT) has evolved into a crucial component of the online education system with the rapid development of online adaptive learning. A key component of the online education system, knowledge tracing (KT) assesses the state of knowledge by tracing each learner’s learning activities. The deep KT model, however, is unable to completely extract the features of the questions and skills due to the heterogeneity of the knowledge structure and the sparsity of the interaction records. The model’s capacity to handle diverse data is also restricted by over parameterization. Additionally, rather than focusing solely on a precise fit, Intelligent Tutoring System (ITS) should stress interpretable feedback to the learner. The deep KT approach’s item parameters are still unable to give students useful feedback. This paper proposes to trace learner’s short-term attentional knowledge based on heterogeneous hierarchical differentiation, named HHSKT. Hierarchical heterogeneous knowledge structures and short-term memory enhancement will be used to model the effects of different interaction sequences on learners. Specifically, knowledge structure features are extracted by constructing a heterogeneous graph-based graph information augmentation component. Question differentiation parameters are derived by transforming the TrueSkill system. Besides, learners’ history-related practices are emphasized by windowing attention. Comparing regression-based and deep-based knowledge tracing experiments shows that HHSKT significantly outperforms the state-of-the-art approach on three real-world benchmark datasets (with an average AUC improvement of up to 3%), demonstrating the superiority of the proposed model.

Two New Diterpenoids from Biscogniauxia sp. and Their Activities.

Two new diterpenoids, including a seco-isopimarane type (1) and an abietane type (2), were isolated from Biscogniauxia sp. (71-10-1-1). Their structures, including absolute configurations, were elucidated by NMR spectroscopic analyses, X-ray crystallography, 13C chemical shifts calculations, and ECD calculations. This is the first report of diterpenoids from Biscogniauxia sp. Furthermore, short-term memory enhancement against Alzheimer’s disease (AD), anti-inflammatory, and cytotoxic activities of 1–2 were also evaluated. The results showed that compound 1 exhibited short-term memory enhancement activity against AD.

Bioassay-Guided Isolation of Anti-Alzheimer Active Components from the Aerial Parts of Hedyotis diffusa and Simultaneous Analysis for Marker Compounds.

Previous studies have reported that Hedyotis diffusa Willdenow extract shows various biological activities on cerebropathia, such as neuroprotection and short-term memory enhancement. However, there has been a lack of studies on the inhibitory activity on neurodegenerative diseases such as Alzheimer’s disease (AD) through enzyme assays of H. diffusa. Therefore, H. diffusa extract and fractions were evaluated for their inhibitory effects through assays of enzymes related to AD, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and on the formation of advanced glycation end-product (AGE). In this study, ten bioactive compounds, including nine iridoid glycosides 1–9 and one flavonol glycoside 10, were isolated from the ethyl acetate and n-butanol fractions of H. diffusa using a bioassay-guided approach. Compound 10 was the strongest inhibitor of cholinesterase, BACE1, and the formation of AGEs of all isolated compounds, while compound 5 had the lowest inhibitory activity. Compounds 3, 6, and 9 exhibited better inhibitory activity than other compounds on AChE, and two pairs of diastereomeric iridoid glycoside structures (compounds 4, 8, and 6, 7) showed higher inhibitory activity than others on BChE. In the BACE1 inhibitory assay, compounds 1–3 were good inhibitors, and compound 10 showed higher inhibitory activity than quercetin, the positive control. Moreover, compounds 1 and 3 were stronger inhibitors of the formation of AGE than aminoguanidine (AMG), the positive control. In conclusion, this study is significant since it demonstrated that the potential inhibitory activity of H. diffusa on enzymes related to AD and showed the potential use for further study as a natural medicine for AD treatment on the basis of the bioactive components isolated from H. diffusa.

Appraising the Neurobehavioural Toxicity Potential of Aqueous Methanol Leaf Extract of Tapinanthus globiferus Growing on Azadirachta indica

The high prevalence and disease burden of anxiety disorders against the paucity and liabilities of existing anxiolytics indicates a need for the discovery of additional/new anti-anxiety agents. However, it is necessary to further screen these new/putative anxiolytic compounds/extracts to rule out the unwanted neurobehavioural toxicities inherent in the existing anti-anxiety drugs. Aqueous methanol leaf extract of Tapinanthus globiferus growing on Azadirachta indica host tree has previously demonstrated significant (p<0.05) anxiolytic effects in mice. This study, therefore, set out to counter-screen this extract for locomotion-suppressant, acute amnesic, sedative (myorelaxant) and hypnotic effects using standard mouse behavioural and biochemical paradigms. The leaf extract (150, 500 and 1500 mg/kg) did not cause significant (p>0.05) alterations in spontaneous locomotor activity, motor coordination/balance, sleep onset or duration, but dose-dependent and significant (p<0.05) increases (63.28±5.63, 65.63±4.12 and 69.18±3.69) in novel object recognition indices of extract-treated compared to 51.54±4.03 and 61.06±2.91 scores in diazepam- and aqua-treated mice, respectively. These findings indicate the aqueous methanol leaf extract is mostly devoid of the evaluated neurobehavioural toxicities and may possess short-term memory enhancement property in mice. These findings may justify the traditional use of Tapinanthus globiferus extracts for memory enhancement.

An Agent-Based Model for the Role of Short-Term Memory Enhancement in the Emergence of Grammatical Agreement.

What is the influence of short-term memory enhancement on the emergence of grammatical agreement systems in multi-agent language games? Agreement systems suppose that at least two words share some features with each other, such as gender, number, or case. Previous work, within the multi-agent language-game framework, has recently proposed models stressing the hypothesis that the emergence of a grammatical agreement system arises from the minimization of semantic ambiguity. On the other hand, neurobiological evidence argues for the hypothesis that language evolution has mainly related to an increasing of short-term memory capacity, which has allowed the online manipulation of words and meanings participating particularly in grammatical agreement systems. Here, the main aim is to propose a multi-agent language game for the emergence of a grammatical agreement system, under measurable long-range relations depending on the short-term memory capacity. Computer simulations, based on a parameter that measures the amount of short-term memory capacity, suggest that agreement marker systems arise in a population of agents equipped at least with a critical short-term memory capacity.

No effect of transcranial direct current stimulation of the dorsolateral prefrontal cortex on short-term memory.

Short-term memory refers to the capacity for holding information in mind for a short period of time with conscious memorization. It is an important ability for daily life and is impaired in several neurological and psychiatric disorders. Anodal transcranial direct current stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) was reported to enhance the capability of short-term memory in healthy subjects. However, results were not consistent and what is the possible impact factor is not known. One important factor that may significantly influence the effect of tDCS is the timing of tDCS administration. In order to explore whether tDCS impact short-term memory and the optimal timing of tDCS administration, we applied anodal tDCS to the left DLPFC to explore the modulatory effect of online and off-line tDCS on digit span as well as visual short-term memory performance in healthy subjects. Results showed tDCS of the left DLPFC did not influence intentional digit span memory performance, whether before the task or during the task. In addition, tDCS of the DLPFC administered before the task showed no effect on visual short-term memory, while there was a trend of increase in false alarm when tDCS of the DLPFC administered during the task. These results did not provide evidence for the enhancement of short-term memory by tDCS of the left DLPFC in healthy subjects, but it suggested an importance of administration time for visual short-term memory. Further studies are required to taking into account the baseline performance of subjects and time-dependence feature of tDCS.

Dimericbiscognienyne A: A Meroterpenoid Dimer from Biscogniauxia sp. with New Skeleton and Its Activity.

Dimericbiscognienyne A (1), an unusual diisoprenyl-cyclohexene-type meroterpenoid dimer, was isolated from Biscogniauxia sp. together with three new monomeric diisoprenyl-cyclohexene-type meroterpenoids (2-4) and one new isoprenyl-benzoic acid-type meroterpenoid (5). All structures were determined by extensive NMR spectroscopic methods, quantum chemical calculations, chemical derivatization, and X-ray crystallography. The formation of 1 is related to a unique intermolecular redox coupling Diels-Alder adduct reaction. Their cytotoxicities and short-term memory enhancement activities against Alzheimer's disease were assessed.

Enhancement of Short-Term Memory by Methyl-6-(Phenylethynyl)-Pyridine in the BTBR T+tf/J Mouse Model of Autism Spectrum Disorder.

BackgroundAutism spectrum disorder (ASD) encompasses a range of disorders that are characterized by social and communication deficits and repetitive behaviors. This study evaluated the effect of methyl-6-(phenylethynyl)-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, on memory enhancement in the BTBR T+tf/J (BTBR) mouse strain, which has been recognized as a model of ASD.MethodsThe pharmacological effects of MPEP on memory and motor coordination were assessed using the Morris water maze and rotarod tests in BTBR and C57BL/6J (B6) mice. Furthermore, we performed morphological analyses of cerebellar foliation in BTBR and B6 mice using hematoxylin and eosin staining.ResultsMPEP-treated BTBR mice exhibited improved learning and memory in the Morris water maze test. MPEP administration also improved motor coordination in the rotarod test. However, no significant difference was observed regarding the numbers of Purkinje cells in the cerebella of BTBR versus normal B6 mice.ConclusionThis study suggests that the mGluR5 antagonist MPEP has the potential to ameliorate learning and memory dysfunction and impaired motor coordination in BTBR mice. These results further suggest that the BTBR mouse model may be useful in pharmacological studies investigating drugs that could potentially alleviate cognitive dysfunction in ASD.

Novel brain penetrant benzofuropiperidine 5-HT6 receptor antagonists

7-Arylsulfonyl substituted benzofuropiperidine was discovered as a novel scaffold for 5HT(6) receptor antagonists. Optimization by substitution at C-1 position led to identification of selective, orally bioavailable, brain penetrant antagonists with reduced hERG liability. An advanced analog tested in rat social recognition model showed significant activity suggesting potential utility in the enhancement of short-term memory.

Enhancement of Learning and Memory by Elevating Brain Magnesium

Learning and memory are fundamental brain functions affected by dietary and environmental factors. Here, we show that increasing brain magnesium using a newly developed magnesium compound (magnesium-L-threonate, MgT) leads to the enhancement of learning abilities, working memory, and short- and long-term memory in rats. The pattern completion ability was also improved in aged rats. MgT-treated rats had higher density of synaptophysin-/synaptobrevin-positive puncta in DG and CA1 subregions of hippocampus that were correlated with memory improvement. Functionally, magnesium increased the number of functional presynaptic release sites, while it reduced their release probability. The resultant synaptic reconfiguration enabled selective enhancement of synaptic transmission for burst inputs. Coupled with concurrent upregulation of NR2B-containing NMDA receptors and its downstream signaling, synaptic plasticity induced by correlated inputs was enhanced. Our findings suggest that an increase in brain magnesium enhances both short-term synaptic facilitation and long-term potentiation and improves learning and memory functions.

Multiple effects of pentyl-4-yn-VPA enantiomers: From toxicity to short-term memory enhancement

2- n-Pentyl-4-pentynoic acid (PE-4-yn-VPA) is a derivative of the antiepileptic and mood-stabilizing drug valproic acid (VPA). PE-4-yn-VPA exists as R- and S-enantiomers, the latter being more teratogenic. PE-4-yn-VPA also possesses antiepileptic, antiproliferative, and cell-differentiating properties. Moreover, the less teratogenic enantiomer, R-PE-4-yn-VPA, was recently shown to improve learning and memory. We here present a detailed investigation of the enantioselective properties of PE-4-yn-VPA using a range of in vitro and in vivo assays including measurements of cellular growth and migration, neuronal differentiation and survival, intracellular signal transduction, synaptic plasticity and maturation, and short-term memory as determined by the social recognition test. The results show that the enantiomers of PE-4-yn-VPA largely had similar effects in vitro. However, in all in vitro experiments the more teratogenic enantiomer, S-PE-4-yn-VPA, exhibited a stronger potency than R-PE-4-yn-VPA, and only S-PE-4-yn-VPA had a detrimental effect on cell survival. Interestingly, both the R- and S-enantiomer improved learning and memory. In contrast, the beneficial effect of S-PE-4-yn-VPA on memory was lost by time, whereas the effect of R-PE-4-yn-VPA administration was longer lasting, suggesting that the beneficial effect of the S-enantiomer on memory formation may be counteracted by its detrimental effect on neuronal cell survival.

Effects of β-carboline alkaloids on the object recognition task in mice

β-carboline alkaloids are found in several medicinal plants and display a variety of actions on the central nervous, muscular and cardiovascular systems. The aim of the present study was to evaluate the effects of systemic administration of β-carboline alkaloids on object recognition in mice. Adult Swiss mice received an intra-peritoneal injection (i.p.) of alkaloids (1.0, 2.5 or 5.0 mg/kg) 30 min before training in an object recognition task. The fully aromatic β-carbolines, harmine and harmol, induced an enhancement of short-term memory (STM) at all doses tested when compared to controls. Harmaline, a dihydro β-carboline and inverse agonist of the MK-801 binding site on the N-methyl- d-aspartate (NMDA) receptor, also induced an enhancement of both short-term memory (STM) and long-term memory (LTM). These results demonstrate that systemic administration of β-carboline alkaloids can improve object recognition memory in mice.

Facilitative Effects of EGb 761 on Olfactory Recognition in Young and Aged Rats

The aim of the present study was to evaluate the effects of chronic and acute treatment by the Gingko biloba extract, EGb 761 (IPSEN, France) on olfactory short-term memory in rats, using a spontaneous recognition procedure. The effects of a daily EGb 761 treatment (30 or 60 mg/kg) over a period of 30 days (Experiment 1) were evaluated in young male rats. Those of a single injection of EGb 761 were assessed either in young male rats at 60 or 120 mg/kg (Experiment 2) or in aged female rats at 60 mg/kg (Experiment 3). Results showed that, at the highest dose (60 mg/kg), chronic EGb 761 treatment enhanced the recognition performances, allowing recognition at delays at which control animals did not show any recognition. Acute treatment enhanced recognition at both doses tested. The results of the third experiment showed that EGb 761 had an overall enhancement effect on the performances of aged rats. In summary, our results provide evidence for a short-term memory enhancement effect of EGb 761 in both young and aged rats.