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Effects of white noise on word recall performance and brain activity in healthy adolescents with normal and low auditory working memory

Othman E, Yusoff AN, Mohamad M, Abdul Manan H, Abd Hamid AI, Giampietro V

Exp Brain Res, 2020 Apr;238(4):945-956.
PMID: 32179941 DOI: 10.1007/s00221-020-05765-3

The present study examined the impact of white noise on word recall performance and brain activity in 40 healthy adolescents, split in two groups (normal and low) depending on their auditory working memory capacity (AWMC). Using functional magnetic resonance imaging, participants performed a backward recall task under four different signal-to-noise ratio (SNR) conditions: 15, 10, 5, and 0-dB SNR. Behaviorally, normal AWMC individuals scored significantly higher than low AWMC individuals across noise levels. Whole-brain analyses showed brain activation not to be statistically different between groups across noise levels. In the normal group, a significant positive relationship was found between performance and number of activated voxels in the right superior frontal gyrus. In the low group, significant positive correlations were found between performance and number of activated voxels in left superior frontal gyrus, left inferior frontal gyrus, and left anterior cingulate cortex. These findings suggest that the strategic structure involved in the enhancement of AWM performance may differ in normal and low AWMC individuals.

Matched MeSH terms: Memory, Short-Term/physiology*
Tualang honey consumption enhanced hippocampal pyramidal count and spatial memory performance of adult male rats

Mohd Amiruddin Kamarulzaidi, Zulkifli Mohd. Yusoff MY, Abdul Majid Mohamed, Durriyyah Sharifah Hasan Adli

Sains Malaysiana, 2016;45:215-220.

As a natural anti-oxidant source, Tualang honey, produced by wild bees nesting on the Tualang tree (Koompassia excelsa) is expected to have positive influence on health, including memory. This study investigated the effect of Tualang honey on the cell count of memory formation related hippocampal pyramidal neuron and on spatial memory performance (SMP) of rats using the radial arm maze (RAM). Sprague Dawley male rats (n=24), 7-8 weeks old were divided into two groups; experimental group group force-fed 1 mL/100 g body weight with 70% honey (HG); and the control group with 0.9% saline (CG) for 12 weeks. Nissl staining technique (with cresyl violet) was employed for neurohistological analysis of the hippocampal tissue. Six randomly selected rats from each group were used for the neuronal soma counting of pyramidal cell layer CA1, CA3a and CA3c regions. Two-way ANOVA analysis showed positively significant differences between treatment and control groups for SMP comparison of working memory and reference memory components, as well as the number of pyramidal neurons. Hence, this positive effects of Tualang honey, as demonstrated behaviorally and neurohistologically, supported report that Tualang honey could improve memory and deter hippocampal morphological impairments; possibly due to its high anti-oxidant properties.

Matched MeSH terms: Memory, Short-Term; Spatial Memory
TRPM4 inhibition improves spatial memory impairment and hippocampal long-term potentiation deficit in chronic cerebral hypoperfused rats

Hazalin NAMN, Liao P, Hassan Z

Behav Brain Res, 2020 09 01;393:112781.
PMID: 32619565 DOI: 10.1016/j.bbr.2020.112781

Chronic cerebral hypoperfusion (CCH) been well characterized as a common pathological status contributing to neurodegenerative diseases such as Alzheimer's disease and vascular dementia. CCH is an important factor that leads to cognitive impairment, but the underlying neurobiological mechanism is poorly understood and no effective treatment is available. Recently, transient receptor potential melastatin 4 (TRPM4) cation channel has been identified as an important molecular element in focal cerebral ischemia. Over activation of the channel is a major molecular mechanism of oncotic cell death. However, the role of TRPM4 in CCH that propagates global brain hypoxia have not been explored. Therefore, the present study is designed to investigate the effect of TRPM4 inhibition on the cognitive functions of the rats following CCH via permanent bilateral occlusion of common carotid arteries (PBOCCA) model. In this model, treatment with siRNA suppressed TRPM4 expression at both the mRNA and protein levels and improved cognitive deficits of the CCH rats without affecting their motor function. Furthermore, treatment with siRNA rescued the LTP impairment in CCH-induced rats. Consistent with the restored of LTP, western blot analysis revealed that siRNA treatment prevented the reduction of synaptic proteins, including calcium/calmodulin-dependent kinase II alpha (CaMKIIα) and brain-derived neurotrophic factor (BDNF) in brain regions of CCH rats. The present findings provide a novel role of TRPM4 in restricting cognitive functions in CCH and suggest inhibiting TRPM4 may represent a promising therapeutic strategy in targeting ion channels to prevent the progression of cognitive deficits induced by ischemia.

Matched MeSH terms: Spatial Memory/physiology*
Effects of modality and repetition in a continuous recognition memory task: Repetition has no effect on auditory recognition memory

Amir Kassim A, Rehman R, Price JM

Acta Psychol (Amst), 2018 Apr;185:72-80.
PMID: 29407247 DOI: 10.1016/j.actpsy.2018.01.012

Previous research has shown that auditory recognition memory is poorer compared to visual and cross-modal (visual and auditory) recognition memory. The effect of repetition on memory has been robust in showing improved performance. It is not clear, however, how auditory recognition memory compares to visual and cross-modal recognition memory following repetition. Participants performed a recognition memory task, making old/new discriminations to new stimuli, stimuli repeated for the first time after 4-7 intervening items (R1), or repeated for the second time after 36-39 intervening items (R2). Depending on the condition, participants were either exposed to visual stimuli (2D line drawings), auditory stimuli (spoken words), or cross-modal stimuli (pairs of images and associated spoken words). Results showed that unlike participants in the visual and cross-modal conditions, participants in the auditory recognition did not show improvements in performance on R2 trials compared to R1 trials. These findings have implications for pedagogical techniques in education, as well as for interventions and exercises aimed at boosting memory performance.

Matched MeSH terms: Memory/physiology
Chronic prenatal restraint stress induced memory impairment in passive avoidance task in post weaned male and female Wistar rats

Cherian SB, Bairy KL, Rao MS

Indian J Exp Biol, 2009 Nov;47(11):893-9.
PMID: 20099462

With a view to examine the effect of chronic maternal stress on cognitive function in the offspring during young age, pregnant Wistar rats were subjected to restraint stress from embryonic day 11 till delivery. Male and female pups born to these stressed rats were subjected to passive avoidance test on postnatal day 30 and 31. Results were compared with rats of the same age and sex born to control mothers, which were not stressed. The results showed that prenatal maternal restraint stress impairs the memory retention during young age in both sexes. The memory retention deficit induced by maternal restraint stress was evident in the decreased latency to enter the dark compartment of passive avoidance apparatus by the rats born to stressed mothers. The observed behavioral deficit may be due to the insult of stress on the developing hippocampus, a structure of the brain concerned with learning and memory. The results suggest that prolonged prenatal stress leads to long lasting malfunction in the behavioral development during young age in both male and female young rats. However when compared to their respective stress naïve controls, it seems evident that prenatal restraint stress has a less effect on females which could be due to their oesterogenic effects. These data reinforce the view that prenatal stress affects cognitive development in a sex-specific manner.

Matched MeSH terms: Memory Disorders/etiology*
Fulltext Nigella sativa Oil Enhances the Spatial Working Memory Performance of Rats on a Radial Arm Maze

Sahak MK, Mohamed AM, Hashim NH, Hasan Adli DS

Evid Based Complement Alternat Med, 2013;2013:180598.
PMID: 24454487 DOI: 10.1155/2013/180598

Nigella sativa, an established historical and religion-based remedy for a wide range of health problems, is a herbal medicine known to have antioxidant and neuroprotective effects. This present study investigated the effect of Nigella sativa oil (NSO) administration on the spatial memory performance (SMP) of male adult rats using eight-arm radial arm maze (RAM). Twelve Sprague Dawley rats (7-9 weeks old) were force-fed daily with 6.0 μ L/100 g body weight of Nigella sativa oil (NSO group; n = 6) or 0.1 mL/100 g body weight of corn oil (control) (CO group; n = 6) for a period of 20 consecutive weeks. For each weekly evaluation of SMP, one day food-deprived rats were tested by allowing each of them 3 minutes to explore the RAM for food as their rewards. Similar to the control group, the SMP of the treated group was not hindered, as indicated by the establishment of the reference and working memory components of the spatial memory. The results demonstrated that lesser mean numbers of error were observed for the NSO-treated group in both parameters as compared to the CO-treated group. NSO could therefore enhance the learning and memory abilities of the rats; there was a significant decrease in the overall mean number of working memory error (WME) in the NSO-treated group.

Matched MeSH terms: Memory, Short-Term; Spatial Memory
Fulltext Neurological effects of honey: current and future prospects

Mijanur Rahman M, Gan SH, Khalil MI

Evid Based Complement Alternat Med, 2014;2014:958721.
PMID: 24876885 DOI: 10.1155/2014/958721

Honey is the only insect-derived natural product with therapeutic, traditional, spiritual, nutritional, cosmetic, and industrial value. In addition to having excellent nutritional value, honey is a good source of physiologically active natural compounds, such as polyphenols. Unfortunately, there are very few current research projects investigating the nootropic and neuropharmacological effects of honey, and these are still in their early stages. Raw honey possesses nootropic effects, such as memory-enhancing effects, as well as neuropharmacological activities, such as anxiolytic, antinociceptive, anticonvulsant, and antidepressant activities. Research suggests that the polyphenol constituents of honey can quench biological reactive oxygen species and counter oxidative stress while restoring the cellular antioxidant defense system. Honey polyphenols are also directly involved in apoptotic activities while attenuating microglia-induced neuroinflammation. Honey polyphenols are useful in improving memory deficits and can act at the molecular level. Therefore, the ultimate biochemical impact of honey on specific neurodegenerative diseases, apoptosis, necrosis, neuroinflammation, synaptic plasticity, and behavior-modulating neural circuitry should be evaluated with appropriate mechanistic approaches using biochemical and molecular tools.

Matched MeSH terms: Memory; Memory Disorders
Fulltext Motor dexterity and strength depend upon integrity of the attention-control system

Rinne P, Hassan M, Fernandes C, Han E, Hennessy E, Waldman A, et al.

Proc Natl Acad Sci U S A, 2018 01 16;115(3):E536-E545.
PMID: 29284747 DOI: 10.1073/pnas.1715617115

Attention control (or executive control) is a higher cognitive function involved in response selection and inhibition, through close interactions with the motor system. Here, we tested whether influences of attention control are also seen on lower level motor functions of dexterity and strength-by examining relationships between attention control and motor performance in healthy-aged and hemiparetic-stroke subjects (n = 93 and 167, respectively). Subjects undertook simple-tracking, precision-hold, and maximum force-generation tasks, with each hand. Performance across all tasks correlated strongly with attention control (measured as distractor resistance), independently of factors such as baseline performance, hand use, lesion size, mood, fatigue, or whether distraction was tested during motor or nonmotor cognitive tasks. Critically, asymmetric dissociations occurred in all tasks, in that severe motor impairment coexisted with normal (or impaired) attention control whereas normal motor performance was never associated with impaired attention control (below a task-dependent threshold). This implies that dexterity and force generation require intact attention control. Subsequently, we examined how motor and attention-control performance mapped to lesion location and cerebral functional connectivity. One component of motor performance (common to both arms), as well as attention control, correlated with the anatomical and functional integrity of a cingulo-opercular "salience" network. Independently of this, motor performance difference between arms correlated negatively with the integrity of the primary sensorimotor network and corticospinal tract. These results suggest that the salience network, and its attention-control function, are necessary for virtually all volitional motor acts while its damage contributes significantly to the cardinal motor deficits of stroke.

Matched MeSH terms: Memory/physiology
Vitamin D treatment ameliorates memory function through downregulation of BAX and upregulation of SOD2 mRNA expression in transient global brain ischaemic injury in rats

Zahra F, Sari DCR, Yuniartha R, Alex, Thamrin MM, Melindah T, et al.

Med J Malaysia, 2024 Aug;79(Suppl 4):31-37.
PMID: 39215412

INTRODUCTION: Ischaemic stroke induces oxidative stress with SOD2 downregulation, and BAX upregulation producing apoptosis. Vitamin D is a fat-soluble hormone that has a neuroprotective effect. The aim of this study is to elucidate the role of vitamin D in memory function, oxidative stress and apoptosis in transient global brain schaemic injury (TGBII) model.
MATERIALS AND METHODS: TGBII was performed in male Wistar rats (3 to 5 months, 150 to 300 g) which underwent bilateral common carotid artery occlusion (BCCAO) for 20 minutes, then reperfused for 10 days (BCCAO group, n = 6). Two groups of BCCAO were treated with intraperitoneal injection of calcitriol 0.125 μg/kgBW (VD1 group) and 0.5 μg/kgBW (VD2 group). The spatial memory function was tested using a probe test with Morris water maze (MWM). mRNA expression of BAX and SOD2 were assessed by the RT-PCR method. Meanwhile, immunohistochemical staining was used for identification of SOD2 protein. Statistical analysis is tested using one-way ANOVA followed by post-hoc LSD.
RESULTS: MWM showed a shorter duration in target quadrant of BCCAO group than the SO group, which is associated with BAX upregulation and SOD2 downregulation. The VDtreated groups had longer duration probe test compared to BCCAO. Furthermore, VD-treated groups had a longer duration in probe test with lower mRNA expression of BAX and higher expression of SOD2. However, there was no significant difference in VD1 and VD2. Immunostaining showed a reduced SOD2 signal in pyramidal cell of CA1 area in BCCAO group and ameliorated in VD1 and VD2 groups.
CONCLUSION: Vitamin D ameliorates memory function and attenuates oxidative stress and apoptosis in the TGBII model.

Matched MeSH terms: Memory/drug effects
Fulltext The effects of age on the strategic use of pitch accents in memory for discourse: a processing-resource account

Fraundorf SH, Watson DG, Benjamin AS

Psychol Aging, 2012 Mar;27(1):88-98.
PMID: 21639646 DOI: 10.1037/a0024138

In two experiments, we investigated age-related changes in how prosodic pitch accents affect memory. Participants listened to recorded discourses that contained two contrasts between pairs of items (e.g., one story contrasted British scientists with French scientists and Malaysia with Indonesia). The end of each discourse referred to one item from each pair; these references received a pitch accent that either denoted contrast (L + H* in the ToBI system) or did not (H*). A contrastive accent on a particular pair improved later recognition memory equally for young and older adults. However, older adults showed decreased memory if the other pair received a contrastive accent (Experiment 1). Young adults with low working memory performance also showed this penalty (Experiment 2). These results suggest that pitch accents guide processing resources to important information for both older and younger adults but diminish memory for less important information in groups with reduced resources, including older adults.

Matched MeSH terms: Memory/physiology*
Reversal of memory deficits by Coriandrum sativum leaves in mice

Mani V, Parle M, Ramasamy K, Abdul Majeed AB

J Sci Food Agric, 2011 Jan 15;91(1):186-92.
PMID: 20848667 DOI: 10.1002/jsfa.4171

Coriandrum sativum L., commonly known as coriander and belonging to the family Apiaceae (Umbelliferae), is cultivated throughout the world for its nutritional value. The present study was undertaken to investigate the effects of fresh Coriandrum sativum leaves (CSL) on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. In this study, CSL (5, 10 and 15% w/w of diet) was fed orally with a specially prepared diet for 45 days consecutively to experimental animals. Elevated plus-maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam, scopolamine and ageing-induced amnesia served as the interoceptive behavioral models.

Matched MeSH terms: Memory/drug effects*; Memory Disorders/diet therapy*; Memory Disorders/metabolism
Fulltext Neuroprotective effects of 1`δ-1`-acetoxyeugenol acetate on Aβ(25-35) induced cognitive dysfunction in mice

Jayasingh Chellammal HS, Veerachamy A, Ramachandran D, Gummadi SB, Manan MM, Yellu NR

Biomed Pharmacother, 2019 Jan;109:1454-1461.
PMID: 30551397 DOI: 10.1016/j.biopha.2018.10.189

The progressive accumulation of amyloid beta (Aβ) peptide is neurotoxic and leads to Alzheimer's type dementia. Accumulation of Aβ has been associated with dysfunction of hypothalamic-pituitary-adrenal (HPA) axis and elevated pro-inflammatory cytokines. In this study, we investigated the effect of 1`δ-1`-acetoxyeugenol acetate (DAEA), isolated from Alpinia galanga (L.), on Aβ(25-35) induced neurodegeneration in mice. Mice were treated with three different doses of DAEA (12.5 mg/kg, 25 mg/kg and 50 mg/kg) for 28 days. Aβ(25-35) was injected by intracerebroventricular (i.c.v.) injection on the 15th day of 28 days. Open field, water maze and step-down inhibitory tests were performed on the 27th day to determine the habituation memory, spatial learning, and short- and long-term memory, respectively. Acetylcholinesterase (AChE), Corticosterone, biogenic amines (serotonin and dopamine), tumour necrosis factor-α (TNF-α), and antioxidant parameters such as superoxide dismutase, catalase, glutathione peroxidase and vitamin C were evaluated in brain homogenates after behavioural tests to ascertain the cognitive improvement through neuro-immune-endocrine modulation. The DAEA treatment with 25 mg/kg and 50 mg/kg resulted in significant (p < 0.001) improvement of habituation memory and step-down inhibitory avoidance task. In spatial learning, the cognitive improvement was significantly improved (p < 0.001) by reduction in escape latency. In the biochemical study, the significant (p < 0.001) reduction of AChE indicates the preeminent neuroprotection. Corticosterone and TNF-α were significantly (p < 0.01) reduced and biogenic amines were increased with antioxidant markers, which signify the potential influence of DAEA on neuroprotection. Our investigation revealed that the drug DAEA attenuates stress mediated through the HPA axis and regulates the neuroendocrine and neuroimmune function to improve the cognition. DAEA could be a potential lead candidate for the treatment of neurodegeneration.

Matched MeSH terms: Memory/drug effects; Memory Disorders/drug therapy; Memory Disorders/metabolism
Subjective memory and concentration deficits in medication-free, non-elderly Asians with major depressive disorder: prevalence and their correlates

Srisurapanont M, Bautista D, Chen CH, Wang G, Udomratn P, Eurviriyanukul K

J Affect Disord, 2015 Jan 15;171:105-10.
PMID: 25303026 DOI: 10.1016/j.jad.2014.09.007

BACKGROUND: Subjective cognitive impairment (SCI) in major depressive disorder (MDD) is prevalent and correlated with disability. This study aimed to examine the prevalence rates and correlates of subjective memory deficit (SMD) and subjective concentration deficit (SCD) in medication-free, non-elderly Asians with MDD.
METHODS: The SMD and SCD were assessed by using two items of the Symptom Checklist-90-Revised (SCL-90-R). Other measurements of interest included the Montgomery-Asberg Depression Rating Scale (MADRS), the Fatigue Severity Scale (FSS), the Sheehan Disability Scale (SDS), and the Short Form Health Survey (SF-36). Adjusted odds ratios with 95% confidence intervals were calculated.
RESULTS: Of 515 participants from China, Korea, Malaysia, Singapore, Taiwan, and Thailand, 347 (67.4%) and 377 (73.2%) had SMD and SCD, respectively. In total, 420 participants (81.6%) had SMD alone, SCD alone, and both deficits. Severe depression and poor mental health were significant correlates of SMD. Severe depression, clinically significant disability, poor physical health, and poor mental health were significantly independent correlates of SCD. Compared with young adults (18-34 years), older adults aged 50-65 years had a significantly lower risk of SCD (OR=.33, 95% CI: .19-.57).
LIMITATIONS: Only two SCL-90-R items were used to assess the SMD and SCD. The exclusion of MDD patients treated with psychotropic medications eliminated many patients commonly seen in typical clinic settings.
CONCLUSION: SMD and SCD are prevalent in medication-free, non-elderly Asians with MDD. Both deficits are correlated with depression and mental health status. The independent correlation between SCD and disability underscores the crucial role of SCI in MDD.
KEYWORDS: Asian; Cognitive impairment; Depressive disorders; SCL-90-R; Subjective

Matched MeSH terms: Memory Disorders/ethnology*; Memory Disorders/psychology
How Can We Best Screen for Cognitive Impairment in Malaysia? A Pilot of the IDEA Cognitive Screen and Picture-Based Memory Impairment Scale and Comparison of Criterion Validity with the Mini Mental State Examination

Rosli R, Tan MP, Gray WK, Subramanian P, Mohd Hairi NN, Chin AV

Clin Gerontol, 2017 03 29;40(4):249-257.
PMID: 28459304 DOI: 10.1080/07317115.2017.1311978

OBJECTIVES: To pilot two new cognitive screening tools for use in an urban Malaysian population and to compare their criterion validity against a gold standard, the well-established Mini-Mental State Examination (MMSE).

METHODS: The IDEA cognitive screen, Picture-based Memory Impairment Scale (PMIS), and MMSE were administered to a convenience sample of elderly (≥ 65 years) from the community and outpatient clinics at an urban teaching hospital. Consensus diagnosis was performed by two geriatricians blinded to PMIS and IDEA cognitive screen scores using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) clinical criteria. The MMSE performance was used as a reference.

RESULTS: The study enrolled 66 participants, with a median age of 78.5 years (interquartile range [IQR], 72.5-83.0) years and 11.0 median years of education (IQR, 9.0-13.0). Forty-three (65.2%) were female, and 32 (48.4%) were Chinese. The area under the receiver operating characteristic (AUROC) curve values were .962 (IDEA cognitive screen), .970 (PMIS), and .935 (MMSE). The optimal cutoff values for sensitivity and specificity were: IDEA cognitive screen: ≤ 11, 90.9% and 89.7%; PMIS: ≤ 6, 97.3% and 69.0%; and MMSE: ≤ 23, 84.6% and 76.0%. Although the sample size was small, multivariable logistic regression modelling suggested that all three screen scores did not appear to be educationally biased.

CONCLUSION: The IDEA and PMIS tools are potentially valid screening tools for dementia in urban Malaysia, and perform at least as well as the MMSE. Further work on larger representative, cohorts is needed to further assess the psychometric properties.

CLINICAL IMPLICATIONS: Study provides alternative screening tools for dementia for both non-specialists and specialists.

Matched MeSH terms: Memory Disorders/classification; Memory Disorders/diagnosis*
Fulltext Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica

Wong JH, Muthuraju S, Reza F, Senik MH, Zhang J, Mohd Yusuf Yeo NAB, et al.

Biomed Pharmacother, 2019 Feb;110:168-180.
PMID: 30469081 DOI: 10.1016/j.biopha.2018.11.044

Centella asiatica (CA) is a widely used traditional herb, notably for its cognitive enhancing effect and potential to increase synaptogenesis. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs) mediate fast excitatory neurotransmission with key roles in long-term potentiation which is believed to be the cellular mechanism of learning and memory. Improved learning and memory can be an indication to the surface expression level of these receptors. Our previous study demonstrated that administration of CA extract improved learning and memory and enhanced expression of AMPAR GluA1 subunit while exerting no significant effects on GABAA receptors of the hippocampus in rats. Hence, to further elucidate the effects of CA, this study investigated the effects of CA extract in recognition memory and spatial memory, and its effects on AMPAR GluA1 and GluA2 subunit and NMDAR GluN2 A and GluN2B subunit expression in the entorhinal cortex (EC) and hippocampal subfields CA1 and CA3. The animals were administered with saline, 100 mg/kg, 300 mg/kg, and 600 mg/kg of CA extract through oral gavage for 14 days, followed by behavioural analysis through Open Field Test (OFT), Novel Object Recognition Task (NORT), and Morris Water Maze (MWM) and lastly morphological and immunohistochemical analysis of the surface expression of AMPAR and NMDAR subunits were performed. The results showed that 14 days of administration of 600 mg/kg of CA extract significantly improved memory assessed through NORT while 300 mg/kg of CA extract significantly improved memory of the animals assessed through MWM. Immunohistochemical analysis revealed differential modulation effects on the expressions of receptor subunits across CA1, CA3 and EC. The CA extract at the highest dose (600 mg/kg) significantly enhanced the expression of AMPAR subunit GluA1 and GluA2 in CA1, CA3 and EC, and NMDAR subunit GluN2B in CA1 and CA3 compared to control. At 300 mg/kg, CA significantly increased expression of AMPAR GluA1 in CA1 and EC, and GluA2 in CA1, CA3 and EC while 100 mg/kg of CA significantly increased expression of only AMPAR subunit GluA2 in CA3 and EC. Expression of NMDAR subunit GluN2 A was significantly reduced in the CA3 (at 100, 300, and 600 mg/kg) while no significant changes of subunit expression was observed in CA1 and EC compared to control. The results suggest that the enhanced learning and memory observed in animals administered with CA was mainly mediated through increased expression of AMPAR GluA1 and GluA2 subunits and differential expression of NMDAR GluN2 A and GluN2B subunits in the hippocampal subfields and EC. With these findings, the study revealed a new aspect of cognitive enhancing effect of CA and its therapeutic potentials through modulating receptor subunit expression.

Matched MeSH terms: Spatial Memory/drug effects*; Spatial Memory/physiology
In silico studies, synthesis and pharmacological evaluation to explore multi-targeted approach for imidazole analogues as potential cholinesterase inhibitors with neuroprotective role for Alzheimer's disease

Gurjar AS, Darekar MN, Yeong KY, Ooi L

Bioorg Med Chem, 2018 05 01;26(8):1511-1522.
PMID: 29429576 DOI: 10.1016/j.bmc.2018.01.029

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with multiple factors associated with its pathogenesis. Our strategy against AD involves design of multi-targeted 2-substituted-4,5-diphenyl-1H-imidazole analogues which can interact and inhibit AChE, thereby, increasing the synaptic availability of ACh, inhibit BuChE, relieve induced oxidative stress and confer a neuroprotective role. Molecular docking was employed to study interactions within the AChE active site. In silico ADME study was performed to estimate pharmacokinetic parameters. Based on computational studies, some analogues were synthesized and subjected to pharmacological evaluation involving antioxidant activity, toxicity and memory model studies in animals followed by detailed mechanistic in vitro cholinesterase inhibition study. Amongst the series, analogue 13 and 20 are the most promising multi-targeted candidates which can potentially increase memory, decrease free radical levels and protect neurons against cognitive deficit.

Matched MeSH terms: Memory Disorders/drug therapy; Memory Disorders/metabolism
Lactobacilli-fermented cow's milk attenuated lipopolysaccharide-induced neuroinflammation and memory impairment in vitro and in vivo

Musa NH, Mani V, Lim SM, Vidyadaran S, Abdul Majeed AB, Ramasamy K

J Dairy Res, 2017 Nov;84(4):488-495.
PMID: 29154736 DOI: 10.1017/S0022029917000620

Nutritional interventions are now recommended as strategies to delay Alzheimer's disease (AD) progression. The present study evaluated the neuroprotective effect (anti-inflammation) of lactic acid bacteria (either Lactobacillus fermentum LAB9 or L. casei LABPC) fermented cow's milk (CM) against lipopolysaccharide (LPS)-activated microglial BV2 cells in vitro. The ability of CM-LAB in attenuating memory deficit in LPS-induced mice was also investigated. ICR mice were orally administered with CM-LAB for 28 d before induction of neuroinflammation by LPS. Learning and memory behaviour were assessed using the Morris Water Maze Test. Brain tissues were homogenised for measurement of acetylcholinesterase (AChE), antioxidative, lipid peroxidation (malondialdehyde (MDA)) and nitrosative stress (NO) parameters. Serum was collected for cytokine analysis. CM-LAB9 and CM-LABPC significantly (P < 0·05) decreased NO level but did not affect CD40 expression in vitro. CM-LAB attenuated LPS-induced memory deficit in mice. This was accompanied by significant (P < 0·05) increment of antioxidants (SOD, GSH, GPx) and reduction of MDA, AChE and also pro-inflammatory cytokines. Unfermented cow's milk (UCM) yielded greater cytokine lowering effect than CM-LAB. The present findings suggest that attenuation of LPS-induced neuroinflamation and memory deficit by CM-LAB could be mediated via anti-inflammation through inhibition of AChE and antioxidative activities.

Matched MeSH terms: Memory Disorders/chemically induced; Memory Disorders/prevention & control*
Fulltext Chicken Essence for Cognitive Function Improvement: A Systematic Review and Meta-Analysis

Teoh SL, Sudfangsai S, Lumbiganon P, Laopaiboon M, Lai NM, Chaiyakunapruk N

Nutrients, 2016 Jan;8(1).
PMID: 26805876 DOI: 10.3390/nu8010057

Chicken essence (CE) is a popular traditional remedy in Asia, which is believed to improve cognitive functions. CE company claimed that the health benefits were proven with research studies. A systematic review was conducted to determine the cognitive-enhancing effects of CE. We systematically searched a number of databases for randomized controlled trials with human subjects consuming CE and cognitive tests involved. Cochrane's Risk of Bias (ROB) tool was used to assess the quality of trials and meta-analysis was performed. Seven trials were included, where six healthy subjects and one subject with poorer cognitive functions were recruited. One trial had unclear ROB while the rest had high ROB. For executive function tests, there was a significant difference favoring CE (pooled standardized mean difference (SMD) of -0.55 (-1.04, -0.06)) and another with no significant difference (pooled SMD of 0.70 (-0.001, 1.40)). For short-term memory tests, no significant difference was found (pooled SMD of 0.63 (-0.16, 1.42)). Currently, there is a lack of convincing evidence to show a cognitive enhancing effect of CE.

Matched MeSH terms: Memory, Short-Term
Modulation of the Nitrergic Pathway via Activation of PPAR-γ Contributes to the Neuroprotective Effect of Pioglitazone Against Streptozotocin-Induced Memory Dysfunction

Prakash A, Kumar A, Ming LC, Mani V, Majeed AB

J Mol Neurosci, 2015 Jul;56(3):739-50.
PMID: 25854775 DOI: 10.1007/s12031-015-0508-7

Alzheimer's disease (AD) is a neurodegenerative disease characterized by impaired memory function and oxidative damage. NO is a major signaling molecule produced in the central nervous system to modulate neurological activity through modulating nitric oxide synthase. Recently, PPAR-γ agonists have shown neuroprotective effects in neurodegenerative disorders. However, there have been only a few studies identifying mechanisms through which cognitive benefits may be exerted. The present study was designed to investigate the possible nitric oxide mechanism in the protective effect of pioglitazone against streptozotocin (STZ)-induced memory dysfunction. Wistar rats were intracerebroventricularly (ICV) injected with STZ. Then rats were treated with pioglitazone, NO modulators [L-arginine and nitro-L-arginine methyl ester (L-NAME)] for 21 days. Behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and mito-oxidative parameters, TNF-α, IL-6, and caspase-3 activity were measured. STZ-treated rats showed a memory deficit and significantly increased in mito-oxidative damage and inflammatory mediators and apoptosis in the hippocampus. Chronic treatment of pioglitazone significantly improved memory retention and attenuated mito-oxidative damage parameters, inflammatory markers, and apoptosis in STZ-treated rats. However, L-arginine pretreatment with lower dose of pioglitazone has not produced any protective effect as compared to per se. Furthermore, pretreatment of L-NAME significantly potentiated its protective effect, which indicates the involvement of nitric oxide for activation of PPAR-γ action. These results demonstrate that pioglitazone offers protection against STZ-induced memory dysfunction possibly due to its antioxidant, anti-inflammatory, and anti-apoptotic action mediating nitric oxide pathways and, therefore, could have a therapeutic potential in AD.

Matched MeSH terms: Memory Disorders/drug therapy*; Memory Disorders/etiology; Memory Disorders/metabolism
Long lead time drought forecasting using lagged climate variables and a stacked long short-term memory model

Dikshit A, Pradhan B, Alamri AM

Sci Total Environ, 2021 Feb 10;755(Pt 2):142638.
PMID: 33049536 DOI: 10.1016/j.scitotenv.2020.142638

Drought forecasting with a long lead time is essential for early warning systems and risk management strategies. The use of machine learning algorithms has been proven to be beneficial in forecasting droughts. However, forecasting at long lead times remains a challenge due to the effects of climate change and the complexities involved in drought assessment. The rise of deep learning techniques can solve this issue, and the present work aims to use a stacked long short-term memory (LSTM) architecture to forecast a commonly used drought measure, namely, the Standard Precipitation Evaporation Index. The model was then applied to the New South Wales region of Australia, with hydrometeorological and climatic variables as predictors. The multivariate interpolated grid of the Climatic Research Unit was used to compute the index at monthly scales, with meteorological variables as predictors. The architecture was trained using data from the period of 1901-2000 and tested on data from the period of 2001-2018. The results were then forecasted at lead times ranging from 1 month to 12 months. The forecasted results were analysed in terms of drought characteristics, such as drought intensity, drought onset, spatial extent and number of drought months, to elucidate how these characteristics improve the understanding of drought forecasting. The drought intensity forecasting capability of the model used two statistical metrics, namely, the coefficient of determination (R2) and root-mean-square error. The variation in the number of drought months was examined using the threat score technique. The results of this study showed that the stacked LSTM model can forecast effectively at short-term and long-term lead times. Such findings will be essential for government agencies and can be further tested to understand the forecasting capability of the presented architecture at shorter temporal scales, which can range from days to weeks.

Matched MeSH terms: Memory, Short-Term

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