Cognitive Enhancing Effects Research Articles

Chronic Nicotine Treatment During Adolescence Attenuates the Effects of Acute Nicotine in Adult Contextual Fear Learning.

Adolescent onset of nicotine abuse is correlated with worse chances at successful abstinence in adulthood. One reason for this may be due to enduring learning deficits resulting from nicotine use during adolescence. Previous work has indicated that chronic nicotine administration beginning in late adolescence (PND38) caused learning deficits in contextual fear when tested in adulthood. The purpose of this study was to determine if chronic nicotine treatment during adolescence would alter sensitivity to nicotine's cognitive enhancing properties in adulthood. C57BL/6J mice received saline or chronic nicotine (12.6mg/kg/day) during adolescence (postnatal day 38) or adulthood (postnatal day 54) for a period of 12 days. Following a 30-day protracted abstinence, mice received either an acute injection of saline or nicotine (0.045, 0.18, and 0.36mg/kg) prior to training and testing a mouse model of contextual fear. It was found that chronic nicotine administration in adult mice did not alter sensitivity to acute nicotine following a protracted abstinence. In adolescent mice, chronic nicotine administration disrupted adult learning and decreased sensitivity to acute nicotine in adulthood as only the highest dose tested (0.36mg/kg) was able to enhance contextual fear learning. These results suggest that adolescent nicotine exposure impairs learning in adulthood, which could increase the risk for continued nicotine use in adulthood by requiring administration of higher doses of nicotine to reverse learning impairments caused by adolescent nicotine exposure. Results from this study add to the growing body of literature suggesting chronic nicotine exposure during adolescence leads to impaired learning in adulthood and demonstrates that nicotine exposure during adolescence attenuates the cognitive enhancing effects of acute nicotine in adulthood, which suggests altered cholinergic function.

Neural effects of methylphenidate and nicotine during smooth pursuit eye movements

IntroductionNicotine and methylphenidate are putative cognitive enhancers in healthy and patient populations. Although they stimulate different neurotransmitter systems, they have been shown to enhance performance on overlapping measures of attention. So far, there has been no direct comparison of the effects of these two stimulants on behavioural performance or brain function in healthy humans. Here, we directly compare the two compounds using a well-established oculomotor biomarker in order to explore common and distinct behavioural and neural effects. MethodsEighty-two healthy male non-smokers performed a smooth pursuit eye movement task while lying in an fMRI scanner. In a between-subjects, double-blind design, subjects either received placebo (placebo patch and capsule), nicotine (7mg nicotine patch and placebo capsule), or methylphenidate (placebo patch and 40mg methylphenidate capsule). ResultsThere were no significant drug effects on behavioural measures. At the neural level, methylphenidate elicited higher activation in left frontal eye field compared to nicotine, with an intermediate response under placebo. DiscussionThe reduced activation of task-related regions under nicotine could be associated with more efficient neural processing, while increased hemodynamic response under methylphenidate is interpretable as enhanced processing of task-relevant networks. Together, these findings suggest dissociable neural effects of these putative cognitive enhancers.

Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice.

The aim of the study is to evaluate the cognitive-enhancing effects of hydrolysate of polygalasaponin (HPS) on senescence accelerate mouse P8 (SAMP8) mice, an effective Alzheimer's disease (AD) model, and to research the relevant mechanisms. The cognitive-enhancing effects of HPS on SAMP8 mice were assessed using Morris water maze (MWM) and step-through passive avoidance tests. Then N-methyl-D-aspartate (NMDA) receptor subunit expression for both the cortex and hippocampus of mice was observed using Western blotting. HPS (25 and 50 mg/kg) improved the escape rate and decreased the escape latency and time spent in the target quadrant for the SAMP8 mice in the MWM after oral administration of HPS for 10 d. Moreover, it decreased error times in the passive avoidance tests. Western blotting showed that HPS was able to reverse the levels of NMDAR1 and NMDAR2B expression in the cortex or hippocampus of model mice. The present study suggested that HPS can improve cognitive deficits in SAMP8 mice, and this mechanism might be associated with NMDA receptor (NMDAR)-related pathways.

Cognition enhancing effect of the aqueous extract of Cinnamomum zeylanicum on non-transgenic Alzheimer's disease rat model: Biochemical, histological, and behavioural studies

Objective: Several dietary supplements are actively being tested for their dual role of alleviating the metabolic perturbations and restricting the consequent cognitive dysfunctions seen in neurodegenerative disorders such as Alzheimer's disease (AD). The aim of the current study was to assess the influence of aqueous extract of cinnamon (CE) on the monosodium glutamate-induced non-transgenic rat model of AD (NTAD) established with insulin resistance, hyperglycaemia, neuronal loss, and cognitive impairment at a very early stage of life.Methods: The experimental design included oral administration of CE (50 mg/kg body weight) for 20 weeks to 2-month and 10-month-old NTAD rats. Following the treatments, the animals attained 7 and 15 months of age, respectively. They were then subjected to behavioural testing, biochemical analysis, and stereology experiments.Results: The results demonstrated that CE treatment improved the insulin sensitivity, increased phosphorylated glycogen synthase kinase-3β (pGSK3β), inhibited the cholinesterase activity, and improved the learning ability in NTAD rats. Histological evaluation has shown an increase in neuron count in the DG sub-field of hippocampus upon treatment with CE.Discussion: These beneficial effects of CE are suggestive of considering cinnamon as a dietary supplement in modulating the metabolic changes and cognitive functions.

Polygalasaponin XXXII, a triterpenoid saponin from Polygalae Radix, attenuates scopolamine-induced cognitive impairments in mice.

Recent studies show that the extract of a Chinese herb Polygalae Radix exerts cognition-enhancing actions in rats and humans. The aim of this study was to characterize the pharmacological profiles of active compounds extracted from Polygalae Radix. Two fractions P3 and P6 and two compounds PTM-15 and polygalasaponin XXXII (PGS32) were prepared. Neuroprotective effects were evaluated in primary cortical neurons exposed to high concentration glutamate, serum deficiency or H2O2. Anti-dementia actions were assessed in scopolamine-induced amnesia in mice using step-through avoidance tests and channel water maze tests. After conducting the channel water maze tests, TrkB phosphorylation in mouse hippocampus was detected using Western blotting. Long-term potentiation (LTP) was induced in the dentate gyrus in adult rats; PGS32 (5 μL 400 μmol/L) was injected into the lateral cerebral ventricle 20 min after high frequency stimulation (HFS). Compared to the fraction P6, the fraction P3 showed more prominent neuroprotective effects in vitro and cognition-enhancing effects in scopolamine-induced amnesia in mice. One active compound PGS32 in the fraction P3 exerted potent cognition-enhancing action: oral administration of PGS32 (0.125 mg·kg(-1)·d(-1)) for 19 days abolished scopolamine-induced memory impairment in mice. Furthermore, PGS32 (0.5 and 2 mg·kg(-1)·d(-1)) significantly stimulated the phosphorylation of TrkB in the hippocampus. Intracerebroventricular injection of PGS32 significantly enhanced HFS-induced LTP in the dentate gyrus of rats. PGS32 attenuates scopolamine-induced cognitive impairments in mice, suggesting that it has a potential for the treatment of cognitive dysfunction and dementia.

<i>Indigofera tinctoria</i> Linn (Fabaceae) attenuates cognitive and behavioral deficits in scopolamine-induced amnesic mice

Purpose: To investigate the cognition-enhancing effects of aqueous extract of Indigofera tinctoria Linn (ITE, Fabaceae) in experimental amnesic mice. Methods : Scopolamine (2 mg/kg, i.p.) was used to induce amnesia in mice. The cognitive-enhancing activity of the ITE (5, 10 and 20 μg/mL) was studied by passive avoidance response, elevated plus maze and Y-maze behavioral paradigm in normal and scopolamine-induced amnesic mice. Antioxidant activities were also determined based on the ability of ITE to inhibit lipid peroxide, superoxide and hydroxyl radicals. Results : Scopolamine-induced cognitive deficits were significantly reversed by ITE (p < 0.001 at 20 mg/kg) in a dose-dependent fashion in all the behavioral paradigms tested. Furthermore, ITE dosedependently scavenged lipid peroxide, superoxide and hydroxyl free radicals with 50 % inhibition concentration (IC 50 ) of 7.28 ± 0.37, 5.25 ± 0.28 and 7.62 ± 0.43 μg/mL, respectively. Conclusion : ITE possesses cognitive-enhancing properties in amnesic mice due to its potent antioxidant action. Keywords : Indigofera tinctoria, Scopolamine, Lipid peroxidation, Amnesia, Antioxidant, Cognition

DADS Analogues Ameliorated the Cognitive Impairments of Alzheimer-Like Rat Model Induced by Scopolamine

The development of agents that affect two or more relevant targets has drawn considerable attention in treatment of AD. Diallyl disulfide (DADS), an active principle of garlic, has been reported to prevent APP processing by amyloidogenic pathway. Recently, we have reported a new series of DADS derivatives and our findings revealed that compound 7k and 7l could provide good templates for developing new multifunctional agents for AD treatment. Thus, the present study was constructed to investigate the neuroprotective effect of DADS analogues (7k and 7l) against Aβ-induced neurotoxicity in SH-SY5Y human neuroblastoma cells and in ameliorating the cognition deficit induced by scopolamine in rat model. The results indicated that compound 7k and 7l significantly inhibited Aβ1-42-induced neuronal cell death by inhibiting ROS generation. Moreover, they prevented apoptosis, in response to ROS, by restoring normal Bax/Bcl-2 ratio. Furthermore, it was observed that scopolamine-induced memory impairment was coupled by alterations in neurotransmitters, acetylcholinesterase activity and oxidative stress markers. Histological analysis revealed severe damaging effects of scopolamine on the structure of cerebral cortex and hippocampus. Administration of compounds 7k and 7l at 5mg/kg significantly reversed scopolamine-induced behavioural, biochemical, neurochemical and histological changes in a manner comparable to standard donepezil. Together the present findings and previous studies indicate that compounds 7k and 7l have neuroprotective and cognition-enhancing effects, which makes them a promising multi-target candidate for addressing the complex nature of AD.

Optogenetic Stimulation of Prefrontal Glutamatergic Neurons Enhances Recognition Memory.

Finding effective cognitive enhancers is a major health challenge; however, modulating glutamatergic neurotransmission has the potential to enhance performance in recognition memory tasks. Previous studies using glutamate receptor antagonists have revealed that the medial prefrontal cortex (mPFC) plays a central role in associative recognition memory. The present study investigates short-term recognition memory using optogenetics to target glutamatergic neurons within the rodent mPFC specifically. Selective stimulation of glutamatergic neurons during the online maintenance of information enhanced associative recognition memory in normal animals. This cognitive enhancing effect was replicated by local infusions of the AMPAkine CX516, but not CX546, which differ in their effects on EPSPs. This suggests that enhancing the amplitude, but not the duration, of excitatory synaptic currents improves memory performance. Increasing glutamate release through infusions of the mGluR7 presynaptic receptor antagonist MMPIP had no effect on performance.SIGNIFICANCE STATEMENT These results provide new mechanistic information that could guide the targeting of future cognitive enhancers. Our work suggests that improved associative-recognition memory can be achieved by enhancing endogenous glutamatergic neuronal activity selectively using an optogenetic approach. We build on these observations to recapitulate this effect using drug treatments that enhance the amplitude of EPSPs; however, drugs that alter the duration of the EPSP or increase glutamate release lack efficacy. This suggests that both neural and temporal specificity are needed to achieve cognitive enhancement.

Cognitive-Enhancing Effect of Dianthus superbus var. Longicalycinus on Scopolamine-Induced Memory Impairment in Mice.

Dianthus superbus (D. superbus) is a traditional crude drug used for the treatment of urethritis, carbuncles and carcinomas. The objective of this study was to confirm the cognitive enhancing effect of D. superbus in memory impairment induced mice and to elucidate the possible potential mechanism. Effect of D. superbus on scopolamine induced memory impairment on mice was evaluated using the Morris water maze and passive avoidance tests. We also investigated acetylcholinesterase (AChE) activity and brain-derived neurotropic factor (BDNF) expression in scopolamine-induced mice. HPLC-DAD analysis was performed to identify active compounds in D. superbus. The results revealed that D. superbus attenuated the learning and memory impairment induced by scopolamine. D. superbus also inhibited AChE levels in the hippocampi of the scopolamine-injected mice. Moreover, D. superbus increased BDNF expression in the hippocampus. Eight compounds were identified using HPLC-DAD analysis. The content of 4-hydroxyphenyl acetic acid was higher than contents of other compounds. These results indicated that D. superbus improved memory functioning accompanied by inhibition of AChE and upregulation of BDNF, suggesting that D. superbus may be a useful therapeutic agent for the prevention or treatment of Alzheimer’s disease.

An exploration of exercise-induced cognitive enhancement and transfer effects to dietary self-control

The primary objective of this study was to examine the effects of aerobic exercise on executive function, specifically inhibitory control, and the transfer to self-control in the dietary domain. It was hypothesized that exercise would enhance inhibitory control, and that this enhancement would facilitate self-control in a laboratory taste test paradigm. Using a crossover design, 51 participants completed counterbalanced sessions of both moderate exercise (experimental condition) and minimal effort walking (control condition) using a treadmill; the intersession interval was 7days. Prior to each exercise bout participants completed a Stroop task. Following each bout participants completed a second Stoop task, as well as a bogus taste test involving three appetitive calorie dense snack foods and two control foods; the amount of each food type consumed during the taste test was covertly measured. Results revealed that moderate exercise significantly improved performance on the Stroop task, and also reduced food consumption during the taste test for appetitive calorie dense snack foods; there was no exercise effect on control food consumption. Exercise-induced gains in Stroop performance mediated the effects of moderate exercise on appetitive snack food consumption. Together these findings provide evidence that a bout of a moderate aerobic exercise can enhance inhibitory control, and support for cross-domain transfer effects to dietary self-control.

Cognitive-Enhancing Herbal Formulae in Korean Medicine: Identification of Candidates by Text Mining and Literature Review.

The main aims of this study were to identify candidates for cognitive-enhancing herbal formulae from the Korean medicine literature and to obtain preliminary data that experimental and clinical researchers could use to develop new cognitive-enhancing drugs. The authors systematically searched for terms related to cognitive enhancement in Dongui Bogam (or Dongyi Baojian), a seminal Korean medicine book. They also reviewed the existing literature on the effects of candidates for cognitive-enhancing herbal formulae and their main constituents. Twenty-three candidates were selected for cognitive-enhancing herbal formulae and their main constituents. For 14 herbal formulae among the 23 candidates, on average 5.6 published research papers per herbal formula describing cognitive-enhancing effects were found. In addition, some published papers were identified for 5 main constituents most frequently used to make up the 23 candidates.

Neuroprotective and Cognition-Enhancing Effects of Compound K Isolated from Red Ginseng.

The present study was aimed at elucidating the effect of compound K derived from red ginseng on memory function in mouse model and glutamate-induced cytotoxicity in mouse hippocampal HT22 cells. Compound K induced antioxidant enzymes in nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated manner, and effectively attenuated cytotoxicity and mitochondrial damage induced by glutamate in HT22 cells. However, the cytoprotective effect by compound K was abolished by heme oxygenase-1 inhibitor, tin protophorphyrin IX, suggesting that neuroprotective effect of compound K was caused by its Nrf2-mediated induction of antioxidant enzymes. Further, memory deficit induced by scopolamine was restored by compound K, which did not inhibit acetylcholine esterase, in C57BL/6 mice but not in Nrf2 knockout mice as assessed by passive avoidance test, Y-maze and water maze tests, suggesting that scopolamine-induced memory impairment was overcome by the induction of Nrf2-mediated antioxidant enzymes by the compound K. Overall, our data indicate that compound K could be useful in prevention and treatment of reactive oxygen species-induced neurological disorders such as Alzheimer's disease.

Oxytocin in social anxiety: An overview

Oxytocin is a neuropeptide that is synthesized in the hypothalamus. It acts as a central neurotransmitter, as well as a peripheral hormone. It is called also trust hormone or love hormone. Because of its anxiolytic, pro-social and social cognitive enhancing effects, oxytocin has been suggested as a promising novel treatment for patients with social anxiety disorder. However, controlled research is small and the studies’ results are inconclusive. I will present the results of several studies with several recommendations about the role of oxytocin in social anxiety disorder. Whereas oxytocin shows some promising effects in resistant cases, of course the preferred agents are SSRIs, SNRIs and CBT.Disclosure of interestThe author has not supplied his declaration of competing interest.

Chicken Essence for Cognitive Function Improvement: A Systematic Review and Meta-Analysis.

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.

Centella asiatica modulates antioxidant and mitochondrial pathways and improves cognitive function in mice

Ethnopharmacological relevanceThis study investigates the cognitive enhancing effects of the plant Centella asiatica which is widely used Ayurvedic and traditional Chinese medicine. Aim of the studyThe goal of this study was to determine the effects of a water extract of the medicinal plant Centella asiatica (CAW) on cognitive ability as well as mitochondrial and antioxidant response pathways in vivo. Materials and methodsOld and young C57BL/6 mice were treated with CAW (2mg/mL) in their drinking water. Learning and memory was assessed using Morris Water Maze (MWM) and then tissue was collected and gene expression analyzed. ResultsCAW improved performance in the MWM in aged animals and had a modest effect on the performance of young animals. CAW also increased the expression of mitochondrial and antioxidant response genes in the brain and liver of both young and old animals. Expression of synaptic markers was also increased in the hippocampus and frontal cortex, but not in the cerebellum of CAW-treated animals. ConclusionsThese data indicate a cognitive enhancing effect of CAW in healthy mice. The gene expression changes caused by CAW suggest a possible effect on mitochondrial biogenesis, which in conjunction with activation of antioxidant response genes could contribute to cognitive improvement.

Black seed oil ameliorated scopolamine-induced memory dysfunction and cortico-hippocampal neural alterations in male Wistar rats

This study was conducted to evaluate cognitive enhancing effect and ameliorative effects of black seed oil in scopolamine induced rat model of cognitive impairment. These effects were investigated on scopolamine-induced dementia model in Morris water maze test (MWM) and Y maze test. The hippocampal histoarchitectural responses to scopolamine and Nigella sativa oil were also examined.Scopolamine (1mg/kgip) was given to induce dementia, followed by oral administration of BSO (1ml/kg) for 14 consecutive days. MWM and Y-maze paradigms were used to assess hippocampal and frontal dependent memory respectively, thereafter the rats were sacrificed and brains were removed for histopathologic studies.Scopolamine resulted in memory impairment, by delayed latency in the MWM, reduced percentage alternation in the Y maze that was coupled by alterations in the cortico-hippocampal neurons. Posttreatment of rats with BSO mitigated scopolamine-induced amnesia, by reducing latency period and increasing percentage alternation and histological changes. The observed anti-amnestic effect of BSO makes it a promising anti-amnesic agent for clinical trials in patients with cognitive impairment.

Comparative safety and effectiveness of cognitive enhancers for Alzheimer's dementia: protocol for a systematic review and individual patient data network meta-analysis

IntroductionAlzheimer's dementia (AD) is the most common cause of dementia, and several organisations, such as the National Institute for Health and Care Excellence, suggest that management of patients with AD...

Evaluation of effect of alcoholic extract of Tinospora cordifolia on learning and memory in alprazolam induced amnesia in albino mice

Background: Tinospora cordifolia is one of the most versatile shrub with cognitive enhancing effects could be beneficial for treatment of dementia and neurodegenerative diseases like alzheimer’s disease. The purpose of study was to evaluate the effect of Tinospora cordifolia on learning and memory in alprazolam induced amnesia in albino mice.Methods: The study was carried out on albino mice, divided into 4 groups of 6 animals each (either sex, 3-4 months of age, weight 25-30g). Amnesia was induced by administering alprazolam (2 mg/kg body weight for 14 days) in all 4 groups for 14 days from 1st to 14th day. Group 1 was given alprazolam (2 mg/kg/p.o) alone for 14 days. In addition, group 2 was given piracetam (400 mg/kg p.o) from 8th to 15th day. Group 3 was given alcoholic extract of Tinospora cordifolia 140 mg/kg, p.o. from 1st to 15th day. Group 4 was given alcoholic extract of Tinospora cordifolia 280 mg/kg, p.o. from 1st to 15th day. The learning and memory of the animals was assessed by employing elevated plus maze (EPM) and step-down type passive avoidance model (SDA).Results: Results were compared among the different groups using one way-ANOVA followed by post hoc Tukey’s test. The measured parameters were compared with standard drug piracetam. Tinospora cordifolia at 140 mg/kg (p&lt;0.02) and 280 mg/kg was significant in both models (p&lt;0.02) and in EPM model, Tinospora cordifolia at 280 mg/kg showed highly significant result (P&lt;0.01).Conclusions: Tinospora cordifolia, Indian medicinal plant useful for treatment of various ailments can also be a useful alternative for treating dementia and associated diseases like alzheimer’s disease.

Compound K derived from ginseng: neuroprotection and cognitive improvement.

The evidence for the neuroprotective and cognitive effects of compound K, a metabolite biotransformed from ginsenosides Rb1, Rb2, and Rc, is reviewed here. Compound K is more bioavailable than other ginsenosides and therefore has greater potential to exert bioactive functions in the body. Although the capability of compound K to cross the blood-brain barrier is not clear, it has been reported to have neuroprotective and cognition enhancing effects and decrease inflammatory biomarkers in animal models of Alzheimer's disease and cerebral ischemia. The plethora of potential health benefits of compound K warrants further research to evaluate its biochemical mechanisms and its ability to protect healthy populations from neurodegenerative diseases.

Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal LPS exposure: a study in rats.

ABSTRACTMaternal exposure to infectious agents is a predisposing factor for schizophrenia with associated cognitive deficits in offspring. A high incidence of smoking in these individuals in adulthood might be, at least in part, due to the cognitive-enhancing effects of nicotine. Here, we have used prenatal exposure to maternal lipopolysaccharide (LPS, bacterial endotoxin) at different time points as a model for cognitive deficits in schizophrenia to determine whether nicotine reverses any associated impairments. Pregnant rats were treated subcutaneously with LPS (0.5 mg/kg) at one of three neurodevelopmental time periods [gestation days (GD) 10-11, 15-16, 18-19]. Cognitive assessment in male offspring commenced in early adulthood [postnatal day (PND) 60] and included: prepulse inhibition (PPI), latent inhibition (LI) and delayed non-matching to sample (DNMTS). Following PND 100, daily nicotine injections (0.6 mg/kg, subcutaneously) were administered, and animals were re-tested in the same tasks (PND 110). Only maternal LPS exposure early during fetal neurodevelopment (GD 10-11) resulted in deficits in all tests compared to animals that had been prenatally exposed to saline at the same gestational time point. Repeated nicotine treatment led to global (PPI) and selective (LI) improvements in performance. Early but not later prenatal LPS exposure induced consistent deficits in cognitive tests with relevance for schizophrenia. Nicotine reversed the LPS-induced deficits in selective attention (LI) and induced a global enhancement of sensorimotor gating (PPI).