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Sample records for memory deficits induced

  1. Lorazepam-Induced Memory Deficits

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    J Gordon Millichap

    1989-01-01

    The effects of low doses of lorazepam (Ativan), 0.03 mg/kg IV, on episodic versus long-term memory, attention, and somatic and affective symptoms were investigated in a group of 16 children aged 2.8 to 14.2 years at St. Jude Children’s Research Hospital, Memphis, and the Center for Pediatric Pharmacokinetics and Therapeutics, Departments of Clinical Pharmacy and Pediatrics, University of Tennessee, Memphis.

  2. Guanfacine ameliorates hypobaric hypoxia induced spatial working memory deficits.

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    Kauser, H; Sahu, S; Kumar, S; Panjwani, U

    2014-01-17

    Hypobaric hypoxia (HH) observed at high altitude causes mild cognitive impairment specifically affecting attention and working memory. Adrenergic dysregulation and neuronal damage in prefrontal cortex (PFC) has been implicated in hypoxia induced memory deficits. Optimal stimulation of alpha 2A adrenergic receptor in PFC facilitates the spatial working memory (SWM) under the conditions of adrenergic dysregulation. Therefore the present study was designed to test the efficacy of alpha 2A adrenergic agonist, Guanfacine (GFC), to restore HH induced SWM deficits and PFC neuronal damage. The rats were exposed to chronic HH equivalent to 25,000ft for 7days in an animal decompression chamber and received daily treatment of GFC at a dose of 1mg/kg body weight via the intramuscular route during the period of exposure. The cognitive performance was assessed by Delayed Alternation Task (DAT) using T-Maze and PFC neuronal damage was studied by apoptotic and neurodegenerative markers. Percentage of correct choice decreased significantly while perseverative errors showed a significant increase after 7days HH exposure, GFC significantly ameliorated the SWM deficits and perseveration. There was a marked and significant increase in chromatin condensation, DNA fragmentation, neuronal pyknosis and fluoro Jade positive cells in layer II of the medial PFC in hypoxia exposed group, administration of GFC significantly reduced the magnitude of these changes. Modulation of adrenergic mechanisms by GFC may serve as an effective countermeasure in amelioration of prefrontal deficits and neurodegenerative changes during HH. © 2013.

  3. Humanin ameliorates diazepam-induced memory deficit in mice.

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    Murakami, Minetaka; Nagahama, Masatoshi; Maruyama, Takuma; Niikura, Takako

    2017-04-01

    Humanin (HN) is an endogenous 24-residue peptide. A highly potent HN derivative, S14G-HN, which has a substitution of serine 14 to glycine, reduced amyloid burden and suppressed cognitive impairment in a mouse model of Alzheimer's disease. S14G-HN also suppressed amnesia induced by a muscarinic receptor antagonist in rodents. To understand the effects of HN on brain function, we tested the effect of S14G-HN on diazepam (DZP)-induced memory impairment and anxiety in mice using the object recognition test and zero-maze test, respectively. Intraperitoneal injection of S14G-HN reversed the DZP-induced memory deficit, whereas no significant change was observed in behavioral markers of anxiety. S14G-HN had no effect on locomotor activity in either test, indicating that S14G-HN did not affect physical functioning or motivation. These results suggest that HN preferentially influences cognitive function but not emotional function in the central nervous system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Effect of Xiaoyaosan Decoction on Learning and Memory Deficit in Rats Induced by Chronic Immobilization Stress

    OpenAIRE

    Meng, Zhen-Zhi; Chen, Jia-Xu; Jiang, You-Ming; Zhang, Han-Ting

    2013-01-01

    Xiaoyaosan (XYS) decoction is a famous prescription which can protect nervous system from stress and treat liver stagnation and spleen deficiency syndrome (LSSDS). In this experiment, we observed the effect of XYS decoction on chronic immobilization stress (CIS) induced learning and memory deficit in rats from behaviors and changes of proteins in hippocampus. We used XYS decoction to treat CIS induced learning and memory deficit in rats with rolipram as positive control, used change of body w...

  5. Transcranial Stimulation of the Dorsolateral Prefrontal Cortex Prevents Stress-Induced Working Memory Deficits.

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    Bogdanov, Mario; Schwabe, Lars

    2016-01-27

    Stress is known to impair working memory performance. This disruptive effect of stress on working memory has been linked to a decrease in the activity of the dorsolateral prefrontal cortex (dlPFC). In the present experiment, we tested whether transcranial direct current stimulation (tDCS) of the dlPFC can prevent stress-induced working memory impairments. We tested 120 healthy participants in a 2 d, sham-controlled, double-blind between-subjects design. Participants completed a test of their individual baseline working memory capacity on day 1. On day 2, participants were exposed to either a stressor or a control manipulation before they performed a visuospatial and a verbal working memory task. While participants completed the tasks, anodal, cathodal, or sham tDCS was applied over the right dlPFC. Stress impaired working memory performance in both tasks, albeit to a lesser extent in the verbal compared with the visuospatial working memory task. This stress-induced working memory impairment was prevented by anodal, but not sham or cathodal, stimulation of the dlPFC. Compared with sham or cathodal stimulation, anodal tDCS led to significantly better working memory performance in both tasks after stress. Our findings indicate a causal role of the dlPFC in working memory impairments after acute stress and point to anodal tDCS as a promising tool to reduce cognitive deficits related to working memory in stress-related mental disorders, such as depression, schizophrenia, or post-traumatic stress disorder. Working memory deficits are prominent in stress-related mental disorders, such as depression, schizophrenia, or post-traumatic stress disorder. Similar working memory impairments have been observed in healthy individuals exposed to acute stress. So far, attempts to prevent such stress-induced working memory deficits focused mainly on pharmacological interventions. Here, we tested the idea that transcranial direct current stimulation of the dorsolateral prefrontal

  6. Effect of xiaoyaosan decoction on learning and memory deficit in rats induced by chronic immobilization stress.

    Science.gov (United States)

    Meng, Zhen-Zhi; Chen, Jia-Xu; Jiang, You-Ming; Zhang, Han-Ting

    2013-01-01

    Xiaoyaosan (XYS) decoction is a famous prescription which can protect nervous system from stress and treat liver stagnation and spleen deficiency syndrome (LSSDS). In this experiment, we observed the effect of XYS decoction on chronic immobilization stress (CIS) induced learning and memory deficit in rats from behaviors and changes of proteins in hippocampus. We used XYS decoction to treat CIS induced learning and memory deficit in rats with rolipram as positive control, used change of body weight and behavioral tests to determine whether the rats have LSSDS and have learning and memory deficit or not. We used Western blotting to determine the content of postsynaptic density protein 95 (PSD-95) and synaptophysin (SYP) in hippocampus. Results showed that XYS could improve the situation of slow weight gain induced by CIS, improve the ability of learning and memory, reverse the symptom of liver stagnation and spleen deficiency syndrome (LSSDS) in rats, and increase the levels of PSD-95 and SYP on the hippocampal nerve synapses. These findings suggested that XYS decoction may be helpful in reversing CIS induced learning and memory deficit by increasing the levels of PSD-95 and SYP on the hippocampal nerve synapses and improving synaptic plasticity.

  7. Effect of Xiaoyaosan Decoction on Learning and Memory Deficit in Rats Induced by Chronic Immobilization Stress

    Directory of Open Access Journals (Sweden)

    Zhen-Zhi Meng

    2013-01-01

    Full Text Available Xiaoyaosan (XYS decoction is a famous prescription which can protect nervous system from stress and treat liver stagnation and spleen deficiency syndrome (LSSDS. In this experiment, we observed the effect of XYS decoction on chronic immobilization stress (CIS induced learning and memory deficit in rats from behaviors and changes of proteins in hippocampus. We used XYS decoction to treat CIS induced learning and memory deficit in rats with rolipram as positive control, used change of body weight and behavioral tests to determine whether the rats have LSSDS and have learning and memory deficit or not. We used Western blotting to determine the content of postsynaptic density protein 95 (PSD-95 and synaptophysin (SYP in hippocampus. Results showed that XYS could improve the situation of slow weight gain induced by CIS, improve the ability of learning and memory, reverse the symptom of liver stagnation and spleen deficiency syndrome (LSSDS in rats, and increase the levels of PSD-95 and SYP on the hippocampal nerve synapses. These findings suggested that XYS decoction may be helpful in reversing CIS induced learning and memory deficit by increasing the levels of PSD-95 and SYP on the hippocampal nerve synapses and improving synaptic plasticity.

  8. Phosphodiesterase 10A inhibition attenuates sleep deprivation-induced deficits in long-term fear memory.

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    Guo, Lengqiu; Guo, Zhuangli; Luo, Xiaoqing; Liang, Rui; Yang, Shui; Ren, Haigang; Wang, Guanghui; Zhen, Xuechu

    2016-12-02

    Sleep, particularly rapid eye movement (REM) sleep, is implicated in the consolidation of emotional memories. In the present study, we investigated the protective effects of a phosphodiesterase 10A (PDE10A) inhibitor MP-10 on deficits in long-term fear memory induced by REM sleep deprivation (REM-SD). REM-SD caused deficits in long-term fear memory, however, MP-10 administration ameliorated the deleterious effects of REM-SD on long term fear memory. Brain-derived neurotropic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) were altered in specific brain regions associated with learning and memory in REM-SD rats. Accordingly, REM-SD caused a significant decrease of pCREB in hippocampus and striatum and a significant decrease of BDNF in the hippocampus, striatum and amygdala, however, MP-10 reversed the effects of REM-SD in a dose-dependent manner. Our findings suggest that REM-SD disrupts the consolidation of long-term fear memory and that administration of MP-10 protects the REM-SD-induced deficits in fear memory, which may be due to the MP-10-induced expression of BDNF in the hippocampus, striatum and amygdala, and phosphorylation of CREB in the hippocampus and striatum. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Hypoxia-induced tau phosphorylation and memory deficit in rats.

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    Zhang, Chang-E; Yang, Xifei; Li, Lingyun; Sui, Xiaojing; Tian, Qing; Wei, Wei; Wang, Jianzhi; Liu, Gongping

    2014-01-01

    Hypoxia was shown to be associated with an increased risk of Alzheimer's disease (AD). The effects of hypoxia on the development of AD pathology and spatial memory ability and the possible molecular mechanisms remain poorly understood. In this study, we demonstrate that rats exposed to a hypoxic condition (10% oxygen concentration) for 1, 2, 4 and 8 weeks (6 h each day) displayed spatial memory impairment and increased tau phosphorylation at Ser198/199/202, Thr205, Ser262, Ser396 and Ser404 in the hippocampus. Concomitantly, the levels of Tyr216-phosphorylated glycogen synthase kinase (GSK)-3β (activated form of GSK-3β) and Tyr307-phosphorylated protein phosphatase 2A (inactivated form of PP2A) were significantly increased in the hippocampus of the rats with 1, 2, 4 and 8 weeks of hypoxia exposure, while the levels of methylated PP2A (activated form of PP2A) were significantly decreased in the hippocampus of the rats with 4 and 8 weeks of hypoxia exposure. In addition, the content of malondialdehyde, an indicator of oxidative stress, was elevated, whereas the activity of superoxide dismutase was not significantly changed in the hippocampus of the rats exposed to hypoxia. Taken together, these data demonstrated that hypoxia induced tau hyperphosphorylation and memory impairment in rats, and that the increased tau phosphorylation could be attributed to activation of GSK-3β and inactivation of PP2A. These data suggest that interventions to improve hypoxia may be helpful to prevent the development of AD pathology and cognitive impairment. © 2014 S. Karger AG, Basel.

  10. Dopamine D1 receptors are responsible for stress-induced emotional memory deficit in mice.

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    Wang, Yongfu; Wu, Jing; Zhu, Bi; Li, Chaocui; Cai, Jing-Xia

    2012-03-01

    It is established that stress impairs spatial learning and memory via the hypothalamus-pituitary-adrenal axis response. Dopamine D1 receptors were also shown to be responsible for a stress-induced deficit of working memory. However, whether stress affects the subsequent emotional learning and memory is not elucidated yet. Here, we employed the well-established one-trial step-through task to study the effect of an acute psychological stress (induced by tail hanging for 5, 10, or 20 min) on emotional learning and memory, and the possible mechanisms as well. We demonstrated that tail hanging induced an obvious stress response. Either an acute tail-hanging stress or a single dose of intraperitoneally injected dopamine D1 receptor antagonist (SCH23390) significantly decreased the step-through latency in the one-trial step-through task. However, SCH23390 prevented the acute tail-hanging stress-induced decrease in the step-through latency. In addition, the effects of tail-hanging stress and/or SCH23390 on the changes in step-through latency were not through non-memory factors such as nociceptive perception and motor function. Our data indicate that the hyperactivation of dopamine D1 receptors mediated the stress-induced deficit of emotional learning and memory. This study may have clinical significance given that psychological stress is considered to play a role in susceptibility to some mental diseases such as depression and post-traumatic stress disorder.

  11. Inhibition of AMPAR endocytosis alleviates pentobarbital-induced spatial memory deficits and synaptic depression.

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    Wang, Wei; Tan, Tao; Yu, Yanzhi; Huang, Zhilin; Du, Yehong; Han, Huili; Dong, Zhifang

    2018-02-26

    Our previous study has shown that pentobarbital causes memory deficits and impairs hippocampal synaptic plasticity. The Tat-GluA2 3Y peptide (GluA2 3Y ) prevents activity-dependent α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) endocytosis. It enables early-phase long-term potentiation (LTP) to proceed to late-phase LTP allowing short-term memory to convert to long-term memory. The purpose of this study is to explore the potential effects of GluA2 3Y on pentobarbital-induced memory deficits through behavioral and electrophysiological paradigms. We found that in vivo intrahippocampal infusion of GluA2 3Y (100μM, 1μl per hippocampus) 30min prior to pentobarbital administration (8mM, 1μl per hippocampus) significantly rescued the pentobarbital-induced deficit of memory retrieval in rats during the Morris water maze test. Pre-incubation of GluA2 3Y (10μM) partially rescued bath application of pentobarbital-induced synaptic transmission of the CA3-CA1 pathway in hippocampal slices. More importantly, GluA2 3Y selectively upregulated the synaptic GluA2 expression that was suppressed by pentobarbital. Together, these results suggest that inhibition of GluA2-containing AMPAR endocytosis by GluA2 3Y increases the pentobarbital-suppressed basal synaptic transmission by upregulating the synaptic GluA2, and then subsequently alleviates spatial memory deficits. Therefore, inhibition of AMPAR endocytosis may be a potential therapeutic way to treat memory disorders caused by anesthetics. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Insight into potential mechanisms of hypobaric hypoxia-induced learning and memory deficit - Lessons from rat studies.

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    Qaid, Eya; Zakaria, R; Sulaiman, S F; Yusof, Na Mohd; Shafin, N; Othman, Z; Ahmad, A H; Aziz, Cb Abd

    2017-12-01

    Impairment of memory is one of the most frequently reported symptoms during sudden hypoxia exposure in human. Cortical atrophy has been linked to the impaired memory function and is suggested to occur with chronic high-altitude exposure. However, the precise molecular mechanism(s) of hypoxia-induced memory impairment remains an enigma. In this work, we review hypoxia-induced learning and memory deficit in human and rat studies. Based on data from rat studies using different protocols of continuous hypoxia, we try to elicit potential mechanisms of hypobaric hypoxia-induced memory deficit.

  13. Stress-induced deficits in working memory and visuo-constructive abilities in Special Operations soldiers.

    Science.gov (United States)

    Morgan, Charles A; Doran, Anthony; Steffian, George; Hazlett, Gary; Southwick, Steven M

    2006-10-01

    Pre-clinical and clinical studies have shown acute stress may impair working memory and visuo-spatial ability. This study was designed to clarify the nature of stress-induced cognitive deficits in soldiers and how such deficits may contribute to operational or battlefield errors. One hundred eighty-four Special Operations warfighters enrolled in Survival School completed pre-stress measures of dissociation and trauma exposure. Subjects were randomized to one of three assessment groups (Pre-stress, Stress, Post-stress) and were administered the Rey Ostereith Complex Figure (ROCF). All subjects completed post-stress measures of dissociation. ROCF copy and recall were normal in the Pre- and Post-stress groups. ROCF copy and recall were significantly impaired in the Stress Group. Stress group ROCF copy performance was piecemeal, and ROCF recall was impaired. Symptoms of dissociation were negatively associated with ROCF recall in the Stress group. Baseline dissociation and history of traumatic stress predicted cognitive impairment during stress. Stress exposure impaired visuo-spatial capacity and working memory. In rats, monkeys, and humans, high dopamine and NE turnover in the PFC induce deficits in cognition and spatial working memory. Improved understanding of stress-induced cognitive deficits may assist in identification of soldiers at risk and lead to the development of better countermeasures.

  14. Ginkgo biloba protects against intermittent hypoxia-induced memory deficits and hippocampal DNA damage in rats.

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    Abdel-Wahab, Basel A; Abd El-Aziz, Samy M

    2012-03-15

    The aim of the present study was to explore the potential protective effect of Ginkgo biloba extract (EGb 761) on intermittent hypoxia (IH)-induced memory deficits and oxidative stress in rats. The passive avoidance reflex (PAR) test was employed to assess the effect of concurrent EGb 761 treatment in different dose levels on the memory deficits that were induced by concurrent long-term exposure to IH (21 days). The levels of hippocampal malondialdehyde (MDA), nitric oxide (NO), and intracellular glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px) were estimated. In addition, serum and hippocampal 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were assessed to study the effect of EGb 761 on hippocampal oxidative DNA damage induced by IH. Exposure to long-term IH in rats induced marked memory impairment that was indicated by a significant decrease in the retention latency in the PAR test. This effect was accompanied by a significant increase in hippocampal oxidative stress and DNA damage. EGb 761 that was administered in either 50- or 100-mg/kg doses per day reversed IH-induced memory deficits, an effect that was accompanied by a significant decrease in hippocampal MDA and NO levels. The antioxidant defence (GSH and GSH-Px) that was depressed by IH was significantly reactivated by EGb 761. Furthermore, serum and hippocampal levels of 8-OHdG that were elevated by IH were significantly reduced. EGb 761 can protect against IH-induced memory impairment, oxidative stress and neuronal DNA damage, possibly through multiple mechanisms involving its potential anti-oxidative effect. Copyright © 2011 Elsevier GmbH. All rights reserved.

  15. Combretum mucronatum and Capparis thonningii prevent scopolamine-induced memory deficit in mice.

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    Ishola, Ismail Ogunbayode; Adeyemi, Olufunmilayo Olaide; Agbaje, Esther Oluwatoyin; Tota, Santoshkumar; Shukla, Rakesh

    2013-01-01

    Roots of Combretum mucronatum Schumach. & Thonn. (Combretaceae) and Capparis thonningii Schum. (Capparaceae) are used in southwest Nigeria in the treatment of inflammatory disorders and mental illness. This study evaluated the antidementic effect of the methanol root extracts of C. mucronatum and C. thonningii on scopolamine (3 mg/kg, i.p.) induced memory impairment in mice. The effect of C. mucronatum and C. thonningii (50-200 mg/kg) administered orally for 3 days on memory impairments induced in mice by scopolamine was assessed in the passive avoidance and Morris water maze test and compared with that of tacrine (5 mg/kg, i.p.). The activities of acetylcholinesterase (AchE) and antioxidant enzymes were estimated in the brain after the completion of behavioral studies. C. mucronatum and C. thonningii root extracts (50-200 mg/kg) reversed scopolamine-induced memory deficit with significant (p memory deficit as a result of significant (p scopolamine-induced increase in oxidative stress parameters as well as restoration of glutathione activity. C. mucronatum and C. thonningii extracts possess significant anticholinesterase, antioxidant and antidementic properties, which may be useful in the management of Alzheimer's disease.

  16. Mercurius solubilis attenuates scopolamine-induced memory deficits and enhances the motor coordination in mice.

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    Kaur, Simranjeet; Kaur, Anudeep; Singh, Gurjit; Bhatti, Rajbir

    2018-03-01

    The present study was designed to investigate the effect of mercurius solubilis (merc sol) on scopolamine induced memory deficits and motor coordination in mice. Three different formulations of merc sol (30X, 200M, 1M) were screened for their in vitro antioxidant potential through DPPH (2, 2-diphenyl-1-picrylhydrazyl) and nitric oxide scavenging activity using response surface methodology. Memory impairment was induced by the administration of scopolamine (1mg/kg i.p.) for 3 days to mice and assessment of memory acquisition and retention was done using Morris water maze test, passive avoidance test, elevated plus maze test, light and dark box test, motor coordination was evaluated using rotarod test and inclined plan test. The involvement of ion channels and nitric oxide pathway in the observed effect of merc sol was elucidated by administration of veratrine (0.125 μg/kg, i.p.), A23187 (20 μg/kg, i.p.), L- arginine (40 mg/kg, i.p.), aminoguanidine (50 mg/kg, i.p.) 30 min prior to merc sol. Acute toxicity studies were performed in accordance with the OECD (Organisation for Economic Co-operation and Development) guidelines. In vitro studies have revealed merc sol 30 X to have maximum free radical and nitric oxide scavenging activity. Administration of merc sol 30 X to mice significantly reduced scopolamine induced memory deficits and motor incoordination in all the performance tasks. The calcium ionophore, A23187 significantly altered the effect of merc sol in mice. No major signs of toxicity were observed. Merc sol has antiamnesic effect in scopolamine induced deficits and motor coordination in mice.

  17. Possible Mechanisms Involved in Attenuation of Lipopolysaccharide-Induced Memory Deficits by Methyl Jasmonate in Mice.

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    Eduviere, Anthony Taghogho; Umukoro, Solomon; Adeoluwa, Olusegun A; Omogbiya, Itivere Adrian; Aluko, Oritoke Modupe

    2016-12-01

    This present study was carried out to investigate the likely mechanisms by which methyl jasmonate (MJ), 'an agent widely used in aromatherapy for neurological disorders, attenuates lipopolysaccharide (LPS)-induced memory deficits in mice. Mice were given intraperitoneal administration of LPS (250 µg/kg) alone or in combination with MJ (10-40 mg/kg), donepezil, DP (1 mg/kg), or vehicle for 7 successive days. Thereafter, memory was assessed using object recognition test (ORT). Acetylcholinesterase and myeloperoxidase activities were estimated in brain tissue homogenates. Brain levels of nitric oxide and markers of oxidative stress as well as histopathologic changes of the prefrontal cortex and cornu ammonis 1 (CA1) of the hippocampal region were also assessed. MJ (10-40 mg/kg) attenuated LPS-induced memory impairment in ORT. Moreover, the increased brain activities of acetylcholinesterase and myeloperoxidase enzymes were suppressed by MJ when compared with control (p memory deficits via mechanisms related to inhibition of acetylcholinesterase, myeloperoxidase, oxidative stress and neuronal degeneration.

  18. The Role of Hippocampal 5HT3 Receptors in Harmaline-Induced Memory Deficit

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    Mohammad Nasehi

    2015-07-01

    Full Text Available Introduction: The plethora of studies indicated that there is a cross talk relationship between harmaline and serotonergic (5-HT system on cognitive and non-cognitive behaviors. Thus, the purpose of this study is to assess the effects of hippocampal 5-HT4 receptor on memory acquisition deficit induced by harmaline.  Methods: Harmaline was injected peritoneally, while 5-HT4 receptor agonist (RS67333 and antagonist (RS23597-190 were injected intra-hippocampal. A single-trial step-down passive avoidance, open field and tail flick tasks were used for measurement of memory, locomotor activity and pain responses, respectively.  Results: The data revealed that pre-training injection of higher dose of harmaline (1 mg/kg, RS67333 (0.5 ng/mouse and RS23597-190 (0.5 ng/mouse decreased memory acquisition process in the adult mice. Moreover, concurrent pre-training administration of subthreshold dose of RS67333 (0.005 ng/mouse or RS23597-190 (0.005 ng/mouse with subthreshold dose of harmaline (0.5 mg/kg, i.p. intensify impairment of memory acquisition. All above interventions did not change locomotion and tail flick behaviors.  Discussion: The results demonstrated that the synergistic effect between both hippocampal 5-HT4 receptor agonist and antagonist with impairment of memory acquisition induced by harmaline, indicating a modulatory effect for hippocampal 5HT4 receptor on Harmaline induced amnesia.

  19. Neuropeptide S overcomes short term memory deficit induced by sleep restriction by increasing prefrontal cortex activity.

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    Thomasson, Julien; Canini, Frédéric; Poly-Thomasson, Betty; Trousselard, Marion; Granon, Sylvie; Chauveau, Frédéric

    2017-12-01

    Sleep restriction (SR) impairs short term memory (STM) that might be related to different processes. Neuropeptide S (NPS), an endogenous neuropeptide that improves short term memory, activates arousal and decreases anxiety is likely to counteract the SR-induced impairment of STM. The objective of the present study was to find common cerebral pathways in sleep restriction and NPS action in order to ultimately antagonize SR effect on memory. The STM was assessed using a spontaneous spatial alternation task in a T-maze. C57-Bl/6J male mice were distributed in 4 groups according to treatment (0.1nmol of NPS or vehicle intracerebroventricular injection) and to 20h-SR. Immediately after behavioural testing, regional c-fos immunohistochemistry was performed and used as a neural activation marker for spatial short term memory (prefrontal cortex, dorsal hippocampus) and emotional reactivity (basolateral amygdala and ventral hippocampus). Anxiety-like behaviour was assessed using elevated-plus maze task. Results showed that SR impaired short term memory performance and decreased neuronal activation in cingular cortex.NPS injection overcame SR-induced STM deficits and increased neuronal activation in infralimbic cortex. SR spared anxiety-like behavior in the elevated-plus maze. Neural activation in basolateral nucleus of amygdala and ventral hippocampus were not changed after SR.In conclusion, the present study shows that NPS overcomes SR-induced STM deficits by increasing prefrontal cortex activation independently of anxiety-like behaviour. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Effects of Different Coumarin- 3-Carboxamide Agents on Scopolamine Induced Learning and Memory Deficit in Mice

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    Samaneh Ghanei Nasab

    2017-06-01

    Full Text Available Introduction: It has been shown that three new synthetic coumarins-3-carboxamides including 3-fluorobenzilchloride, 4-fluorobenzilchloride and 2-hidroxy-3 metoxybenzaldehyde, have acetylcholinesterase inhibitory activity. This study was performed to estimate ameliorating effect of these new coumarin-3-carboxamides on memory impairments induced by scopolamine (1 mg/kg, induced prolongation in mice. Methods: 30 male mice were divided into five groups, 6 mice in each group. Three experiment groups received coumarins-3- carboxamides (10 mg/kg body weight 30 min before scopalamin injection and two other groups considered as normal (saline-treated groups and finally one negative control (scopalamin only group. The experiment groups were treated with coumarins of 3-fluorobenzilchloride, 4-fluorobenzilchloride and 2-hidroxy-3 metoxybenzaldehyde. The passive avoidance test was performed in an automatic conventional shuttle box set-up. The stepped down latency and number of errors was recorded. Results: With reference to saline-treated group, scopolamine-treated mice demonstrated impairment of learning and memory as a reduction of latency and an increased numbers of errors in step-down testp < 0.01. Treated mice receiving these coumarins at the dose of 10 mg/kg showed an increase in the number of avoidances on the memory tests compared to the scopolamine group (p < 0.01. Conclusion: The study has demonstrated some therapeutic effects of coumarin-3-carboxamides on learning and memory deficit induced by scopolamine. Further investigation is needed to explore whether coumarin-3-carboxamides could be beneficial for memory impairment in Alzheimer’s disease in which cholinergic deficit is one of the hallmarks. 

  1. Aerobic exercise attenuates inhibitory avoidance memory deficit induced by paradoxical sleep deprivation in rats.

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    Fernandes, Jansen; Baliego, Luiz Guilherme Zaccaro; Peixinho-Pena, Luiz Fernando; de Almeida, Alexandre Aparecido; Venancio, Daniel Paulino; Scorza, Fulvio Alexandre; de Mello, Marco Tulio; Arida, Ricardo Mario

    2013-09-05

    The deleterious effects of paradoxical sleep deprivation (SD) on memory processes are well documented. Physical exercise improves many aspects of brain functions and induces neuroprotection. In the present study, we investigated the influence of 4 weeks of treadmill aerobic exercise on both long-term memory and the expression of synaptic proteins (GAP-43, synapsin I, synaptophysin, and PSD-95) in normal and sleep-deprived rats. Adult Wistar rats were subjected to 4 weeks of treadmill exercise training for 35 min, five times per week. Twenty-four hours after the last exercise session, the rats were sleep-deprived for 96 h using the modified multiple platform method. To assess memory after SD, all animals underwent training for the inhibitory avoidance task and were tested 24h later. The aerobic exercise attenuated the long-term memory deficit induced by 96 h of paradoxical SD. Western blot analysis of the hippocampus revealed increased levels of GAP-43 in exercised rats. However, the expression of synapsin I, synaptophysin, and PSD-95 was not modified by either exercise or SD. Our results suggest that an aerobic exercise program can attenuate the deleterious effects of SD on long-term memory and that this effect is not directly related to changes in the expression of the pre- and post-synaptic proteins analyzed in the study. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Environmental Enrichment Prevents Methamphetamine-Induced Spatial Memory Deficits and Obsessive-Compulsive Behavior in Rats.

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    Hajheidari, Samira; Miladi-Gorji, Hossein; Bigdeli, Imanollah

    2017-01-01

    Objective: This study was designed to examine the effect of environmental enrichment during methamphetamine (METH) dependency and withdrawal on methamphetamine-induced spatial learning and memory deficits and obsessive-compulsive behavior. Method: Adult male Wistar rats (200 ± 10 g) chronically received bi-daily doses of METH (2 mg/kg, sc, with 12 hours intervals) for 14 days. Rats reared in standard (SE) or enriched environment (EE) during the development of dependence on METH and withdrawal. Then, they were tested for spatial learning and memory (the water maze), and obsessive-compulsive behavior as grooming behavior in METH-withdrawn rats. Results: The results revealed that the Sal/EE and METH/EE rats reared in EE spent more time in the target zone on the water maze and displayed significantly increased proximity to the platform compared to their control groups. METH withdrawn rats reared in EE displayed less grooming behavior than METH/SE group. Conclusion : Our findings revealed EE ameliorates METH-induced spatial memory deficits and obsessive-compulsive behavior in rats.

  3. Environmental Enrichment Prevents Methamphetamine-Induced Spatial Memory Deficits and Obsessive-Compulsive Behavior in Rats

    Directory of Open Access Journals (Sweden)

    Samira Hajheidari

    2017-02-01

    Full Text Available Objective: This study was designed to examine the effect of environmental enrichment during methamphetamine (METH dependency and withdrawal on methamphetamine-induced spatial learning and memory deficits and obsessive-compulsive behavior.Method: Adult male Wistar rats (200 ± 10 g chronically received bi-daily doses of METH (2 mg/kg, sc, with 12 hours intervals for 14 days. Rats reared in standard (SE or enriched environment (EE during the development of dependence on METH and withdrawal. Then, they were tested for spatial learning and memory (the water maze, and obsessive-compulsive behavior as grooming behavior in METH-withdrawn rats.Results: The results revealed that the Sal/EE and METH/EE rats reared in EE spent more time in the target zone on the water maze and displayed significantly increased proximity to the platform compared to their control groups. METH withdrawn rats reared in EE displayed less grooming behavior than METH/SE group.Conclusion: Our findings revealed EE ameliorates METH-induced spatial memory deficits and obsessive-compulsive behavior in rats.

  4. Urtica dioica modulates hippocampal insulin signaling and recognition memory deficit in streptozotocin induced diabetic mice.

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    Patel, Sita Sharan; Gupta, Sahil; Udayabanu, Malairaman

    2016-06-01

    Diabetes mellitus has been associated with functional abnormalities in the hippocampus and performance of cognitive function. Urtica dioica (UD) has been used in the treatment of diabetes. In our previous report we observed that UD extract attenuate diabetes mediated associative and spatial memory dysfunction. The present study aimed to evaluate the effect of UD extract on mouse model of diabetes-induced recognition memory deficit and explore the possible mechanism behind it. Streptozotocin (STZ) (50 mg/kg, i.p. consecutively for 5 days) was used to induce diabetes followed by UD extract (50 mg/kg, oral) or rosiglitazone (ROSI) (5 mg/kg, oral) administration for 8 weeks. STZ induced diabetic mice showed significant decrease in hippocampal insulin signaling and translocation of glucose transporter type 4 (GLUT4) to neuronal membrane resulting in cognitive dysfunction and hypolocomotion. UD treatment effectively improved hippocampal insulin signaling, glucose tolerance and recognition memory performance in diabetic mice, which was comparable to ROSI. Further, diabetes mediated oxidative stress and inflammation was reversed by chronic UD or ROSI administration. UD leaves extract acts via insulin signaling pathway and might prove to be effective for the diabetes mediated central nervous system complications.

  5. Neuroprotective effects of polygalacic acid on scopolamine-induced memory deficits in mice.

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    Guo, Changrun; Shen, Jinyang; Meng, Zhaoqing; Yang, Xiaolin; Li, Fei

    2016-02-15

    Polygala tenuifolia Willd is a Traditional Chinese Medicine used for the treatment of learning and memory deficits. Triterpenoid saponins, the main bioactive compounds of Polygala tenuifolia Willd, are easily hydrolyzed to polygalacic acid (PA). The present study was undertaken to investigate the neuroprotective effects of PA on scopolamine-induced cognitive dysfunction and to elucidate its underlying mechanisms of action. PA (3, 6, and 12 mg/kg) was administered orally to mice for fourteen days, and scopolamine (1 mg/kg) was injected intraperitoneally for fourteen days to induce memory impairment. Memory-related behaviors were evaluated using the Morris water maze. Cholinergic and neuroinflammatory activities were measured in brain tissue. Superoxide dismutase activities, malondialdehyde and reduced glutathione contents were also measured in the brains. Treatment with scopolamine significantly increased the escape latency time, decreased the number of crossings, and shortened the time spent in the target quadrant, while PA reversed these scopolamine-induced effects. PA significantly improved cholinergic system reactivity, as indicated by decreased acetylcholinesterase (AChE) activity, increased choline acetyltransferase (ChAT) activity, and elevated levels of acetylcholine (ACh) in the hippocampus and frontal cortex. PA also significantly ameliorated neuroinflammation and oxidative stress in mice. These results suggest that PA might exert a significant neuroprotective effect on cognitive impairment, driven in part by the modulation of cholinergic activity and neuroinflammation. Copyright © 2015 Elsevier GmbH. All rights reserved.

  6. 5-HT6 receptor blockade differentially affects scopolamine-induced deficits of working memory, recognition memory and aversive learning in mice.

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    Da Silva Costa-Aze, Virginie; Quiedeville, Anne; Boulouard, Michel; Dauphin, François

    2012-07-01

    Blockade of 5-HT6 receptors (5-HT6R) is known to improve cognitive performances in the rodent. This improvement has been hypothesized to be the result, at least in part, of a modulation of the cholinergic neurotransmission. We assessed the effects of 5-HT6R blockade on selected types of memory relevant to functional deficits of ageing and neurodegenerative diseases, in mice that present a scopolamine-induced cholinergic disruption of memory. Following the selection of an adequate dose of scopolamine to induce cognitive deficits, we have studied the effects of the selective 5-HT6R antagonist SB-271046, alone or in combination with scopolamine, on working memory (spontaneous alternation task in the T-maze), recognition memory (place recognition) and aversive learning (passive avoidance). SB-271046 alone failed to affect working memory, recognition memory and aversive learning performances. In contrast, SB-271046 was able to reverse the scopolamine-induced deficits in working memory (only at 30 mg kg⁻¹) and those of acquisition and retrieval of aversive learning (dose-dependent effect); scopolamine-induced deficits in episodic-like memory (acquisition and retrieval) were partially counteracted by 5-HT6R blockade. The modulation between 5-HT6R and the cholinergic system appears to be predominant for working memory and aversive learning, but not for other types of memory (i.e. episodic-like memory). Interactions between 5-HT6R and alternative neurotransmission systems (i.e. glutamatergic system) should be further studied. The respective involvement of these interactions in the memory disorders related to ageing and neurodegenerative diseases is of pivotal importance regarding the possible use of 5-HT6R antagonists in the treatment of memory disorders in humans.

  7. TNF-α from hippocampal microglia induces working memory deficits by acute stress in mice.

    Science.gov (United States)

    Ohgidani, Masahiro; Kato, Takahiro A; Sagata, Noriaki; Hayakawa, Kohei; Shimokawa, Norihiro; Sato-Kasai, Mina; Kanba, Shigenobu

    2016-07-01

    The role of microglia in stress responses has recently been highlighted, yet the underlying mechanisms of action remain unresolved. The present study examined disruption in working memory due to acute stress using the water-immersion resistant stress (WIRS) test in mice. Mice were subjected to acute WIRS, and biochemical, immunohistochemical, and behavioral assessments were conducted. Spontaneous alternations (working memory) significantly decreased after exposure to acute WIRS for 2h. We employed a 3D morphological analysis and site- and microglia-specific gene analysis techniques to detect microglial activity. Morphological changes in hippocampal microglia were not observed after acute stress, even when assessing ramification ratios and cell somata volumes. Interestingly, hippocampal tumor necrosis factor (TNF)-α levels were significantly elevated after acute stress, and acute stress-induced TNF-α was produced by hippocampal-ramified microglia. Conversely, plasma concentrations of TNF-α were not elevated after acute stress. Etanercept (TNF-α inhibitor) recovered working memory deficits in accordance with hippocampal TNF-α reductions. Overall, results suggest that TNF-α from hippocampal microglia is a key contributor to early-stage stress-to-mental responses. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. The Histamine H3 Receptor Antagonist DL77 Ameliorates MK801-Induced Memory Deficits in Rats

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    Nermin Eissa

    2018-02-01

    Full Text Available The role of Histamine H3 receptors (H3Rs in memory, and the prospective of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer disease (AD is well-accepted. For that reason, the procognitive effects of the H3R antagonist DL77 on cognitive impairments induced with MK801 were tested in an inhibitory passive avoidance paradigm (PAP and novel object recognition (NOR task in adult male rats, using donepezil (DOZ as a standard drug. Acute systemic pretreatment with DL77 (2.5, 5, and 10 mg/kg, i.p. significantly ameliorated memory deficits induced with MK801 in PAP (all P < 0.05, n = 7. The ameliorative effect of most promising dose of DL77 (5 mg/kg, i.p. was reversed when rats were co-injected with the H3R agonist R-(α-methylhistamine (RAMH, 10 mg/kg, i.p. (p = 0.701 for MK801-amnesic group vs. MK801+DL77+RAMH group, n = 6. In the NOR paradigm, DL77 (5 mg/kg, i.p. counteracted long-term memory (LTM deficits induced with MK801 (P < 0.05, n = 6–8, and the DL77-provided effect was similar to that of DOZ (p = 0.788, n = 6–8, and was reversed when rats were co-injected with RAMH (10 mg/kg, i.p. (p = 0.877, n = 6, as compared to the (MK801-amnesic group. However, DL77 (5 mg/kg, i.p. did not alter short-term memory (STM impairment in NOR test (p = 0.772, n = 6–8, as compared to (MK801-amnesic group. Moreover, DL77 (5 mg/kg failed to modify anxiety and locomotor behaviors of animals innate to elevated-plus maze (EPM (p = 0.67 for percentage of time spent exploring the open arms, p = 0.52 for number of entries into the open arms, p = 0.76 for percentage of entries into the open arms, and p = 0.73 number of closed arm entries as compared to saline-treated groups, all n = 6, demonstrating that the procognitive effects observed in PAP or NOR tests were unconnected to alterations in emotions or in natural locomotion of tested animals. These results signify the potential involvement of H3Rs in modulating

  9. D-cycloserine in prelimbic cortex reverses scopolamine-induced deficits in olfactory memory in rats.

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    Marta Portero-Tresserra

    Full Text Available A significant interaction between N-methyl-D-aspartate (NMDA and muscarinic receptors has been suggested in the modulation of learning and memory processes. The present study further investigates this issue and explores whether d-cycloserine (DCS, a partial agonist at the glycine binding site of the NMDA receptors that has been regarded as a cognitive enhancer, would reverse scopolamine (SCOP-induced amnesia in two olfactory learning tasks when administered into the prelimbic cortex (PLC. Thus, in experiment 1, DCS (10 µg/site was infused prior to acquisition of odor discrimination (ODT and social transmission of food preference (STFP, which have been previously characterized as paradigms sensitive to PLC muscarinic blockade. Immediately after learning such tasks, SCOP was injected (20 µg/site and the effects of both drugs (alone and combined were tested in 24-h retention tests. To assess whether DCS effects may depend on the difficulty of the task, in the STFP the rats expressed their food preference either in a standard two-choice test (experiment 1 or a more challenging three-choice test (experiment 2. The results showed that bilateral intra-PLC infusions of SCOP markedly disrupted the ODT and STFP memory tests. Additionally, infusions of DCS alone into the PLC enhanced ODT but not STFP retention. However, the DCS treatment reversed SCOP-induced memory deficits in both tasks, and this effect seemed more apparent in ODT and 3-choice STFP. Such results support the interaction between the glutamatergic and the cholinergic systems in the PLC in such a way that positive modulation of the NMDA receptor/channel, through activation of the glycine binding site, may compensate dysfunction of muscarinic neurotransmission involved in stimulus-reward and relational learning tasks.

  10. Oxytocin is implicated in social memory deficits induced by early sensory deprivation in mice.

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    Zhang, Jin-Bao; Chen, Ling; Lv, Zhu-Man; Niu, Xue-Yuan; Shao, Can-Can; Zhang, Chan; Pruski, Michal; Huang, Ying; Qi, Cong-Cong; Song, Ning-Ning; Lang, Bing; Ding, Yu-Qiang

    2016-12-13

    Early-life sensory input plays a crucial role in brain development. Although deprivation of orofacial sensory input at perinatal stages disrupts the establishment of the barrel cortex and relevant callosal connections, its long-term effect on adult behavior remains elusive. In this study, we investigated the behavioral phenotypes in adult mice with unilateral transection of the infraorbital nerve (ION) at postnatal day 3 (P3). Although ION-transected mice had normal locomotor activity, motor coordination, olfaction, anxiety-like behaviors, novel object memory, preference for social novelty and sociability, they presented deficits in social memory and spatial memory compared with control mice. In addition, the social memory deficit was associated with reduced oxytocin (OXT) levels in the hypothalamus and could be partially restored by intranasal administration of OXT. Thus, early sensory deprivation does result in behavioral alterations in mice, some of which may be associated with the disruption of oxytocin signaling.

  11. The effect of BLA GABAB receptors in anxiolytic-like effect and aversive memory deficit induced by ACPA

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    Katayoon Kangarlu Haghighi

    2016-07-01

    Full Text Available Background: As a psychoactive plant, Cannabis sativa (Marijuana is widely used throughout the world. Several investigations have indicated that administration of Marijuana affects various cognitive and non-cognitive behaviors. These include anxiety-like behaviors and learning and memory deficit. It has been shown that three main cannabinoid receptors [i.e. CB1, CB2 and CB3 are involved in cannabinoids’ functions. CB1 receptors are abundantly expressed in the central nervous system regions such as hippocampus, amygdala, cerebellum and the cortex. Therefore, the neuropsychological functions of endocannabinoids are thought to be more linked to CB1 receptors. Among other brain regions, CB1 is highly expressed in the amygdala which is an integral component of the limbic circuitry. The amygdala plays a major role in the control of emotional behavior, including conditioned fear and anxiety. In present study we examined the possible roles of basolateral amygdala (BLA GABAB receptors in arachydonilcyclopropylamide (ACPA-induced anxiolytic-like effect and aversive memory deficit in adult male mice. Methods: This experimental study was conducted from September 2013 to December 2014 in Institute for Studies in Theoretical Physics and Mathematics, School of Cognitive Sciences, Tehran and Male albino NMRI mice (Pasture Institute, Iran, weighting 27-30 g, were used. Bilateral guide-cannulae were implanted to allow intra BLA microinjection of the drugs. We used Elevated Plus Maze (EPM to examine memory and anxiety behavior (test-retest protocol. ACPA administrate intra-peritoneal and GABAB agonist and antagonist administrated intra-amygdala. Results: Data showed that pre-test treatment with ACPA induced anxiolytic-like and aversive memory deficit The results revealed that pre-test intra-BLA infusion of baclofen (GABAB receptor agonist impaired the aversive memory while phaclofen (GABAB receptor antagonist improved it. Interestingly, pretreatment with a sub

  12. Hippocampal brain-derived neurotrophic factor mediates recovery from chronic stress-induced spatial reference memory deficits.

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    Ortiz, J Bryce; Mathewson, Coy M; Hoffman, Ann N; Hanavan, Paul D; Terwilliger, Ernest F; Conrad, Cheryl D

    2014-11-01

    Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain-derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress-induced spatial memory deficits. Adult male Sprague-Dawley rats were infused into the dorsal hippocampal cornu ammonis (CA)3 region with an adeno-associated viral vector containing the sequence for a short hairpin RNA (shRNA) directed against BDNF or a scrambled sequence (Scr). Rats were then chronically restrained (wire mesh, 6 h/day for 21 days) and assessed for spatial learning and memory using a radial arm water maze (RAWM) either immediately after stressor cessation (Str-Imm) or following a 21-day post-stress recovery period (Str-Rec). All groups learned the RAWM task similarly, but differed on the memory retention trials. Rats in the Str-Imm group, regardless of adeno-associated viral contents, committed more errors in the spatial reference memory domain on the single retention trial during day 3 than did the non-stressed controls. Importantly, the typical improvement in spatial memory following the recovery from chronic stress was blocked with the shRNA against BDNF, as Str-Rec-shRNA performed worse on the RAWM compared with the non-stressed controls or Str-Rec-Scr. The stress effects were specific for the reference memory domain, but knockdown of hippocampal BDNF in unstressed controls briefly disrupted spatial working memory as measured by repeated entry errors on day 2 of training. These results demonstrated that hippocampal BDNF was necessary for the recovery from stress-induced hippocampal-dependent spatial memory deficits in the reference memory domain. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Reversal of Trimethyltin-Induced Learning and Memory Deficits by 3,5-Dicaffeoylquinic Acid

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    Jin Yong Kang

    2016-01-01

    Full Text Available The antiamnesic effect of 3,5-dicaffeoylquinic acid (3,5-diCQA as the main phenolic compound in Artemisia argyi H. extract on cognitive dysfunction induced by trimethyltin (TMT (7.1 μg/kg of body weight; intraperitoneal injection was investigated in order to assess its ameliorating function in mice. In several behavioral tests, namely, the Y-maze, passive avoidance, and Morris water maze (MWM test, 3,5-diCQA significantly ameliorated learning and memory deficits. After the behavioral tests, brain tissues from the mice were analyzed to characterize the basis of the neuroprotective effect. Acetylcholine (ACh levels increased, whereas the activity of acetylcholinesterase (AChE decreased upon administration of 3,5-diCQA. In addition, 3,5-diCQA effectively protected against an increase in malondialdehyde (MDA content, an increase in the oxidized glutathione (GSH ratio, and a decline of total superoxide dismutase (SOD level. 3,5-diCQA may prevent neuronal apoptosis through the protection of mitochondrial activities and the repression of apoptotic signaling molecules such as p-Akt, BAX, and p-tau (Ser 404.

  14. Spatial learning and memory deficits induced by exposure to iron-56-particle radiation

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    Shukitt-Hale, B.; Casadesus, G.; McEwen, J. J.; Rabin, B. M.; Joseph, J. A.

    2000-01-01

    It has previously been shown that exposing rats to particles of high energy and charge (HZE) disrupts the functioning of the dopaminergic system and behaviors mediated by this system, such as motor performance and an amphetamine-induced conditioned taste aversion; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, spatial learning and memory were assessed in the Morris water maze 1 month after whole-body irradiation with 1.5 Gy of 1 GeV/nucleon high-energy (56)Fe particles, to test the cognitive behavioral consequences of radiation exposure. Irradiated rats demonstrated cognitive impairment compared to the control group as seen in their increased latencies to find the hidden platform, particularly on the reversal day when the platform was moved to the opposite quadrant. Also, the irradiated group used nonspatial strategies during the probe trials (swim with no platform), i.e. less time spent in the platform quadrant, fewer crossings of and less time spent in the previous platform location, and longer latencies to the previous platform location. These findings are similar to those seen in aged rats, suggesting that an increased release of reactive oxygen species may be responsible for the induction of radiation- and age-related cognitive deficits. If these decrements in behavior also occur in humans, they may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.

  15. Beneficial Effects of Gagam-Palmultang on Scopolamine-Induced Memory Deficits in Mice

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    Yu Ri Kim

    2018-01-01

    Full Text Available From text mining of Dongeuibogam, the 7 herbs in Palmultang can be considered effective candidates for memory enhancement. We sought to determine whether Gagam-Palmultang, comprising these 7 herbs, ameliorates scopolamine-induced memory impairment in mice, by focusing on the central cholinergic system and memory-related signaling molecules. Behavioral tests were performed after inducing memory impairment by scopolamine administration. The cholinergic system activity and memory-related molecules were examined in the hippocampus by enzyme-linked immunosorbent, western blot, and immunofluorescence assays. Gagam-Palmultang ameliorated scopolamine-induced memory impairment in the Morris water maze test, producing a significant improvement in the mean time required to find the hidden platform. Treatment with Gagam-Palmultang reduced acetylcholinesterase activity and expression in the hippocampus induced by scopolamine. The diminished phosphorylated phosphatidylinositide 3-kinase (PI3K, extracellular signal-regulated kinase (ERK, cAMP response element-binding protein (CREB, and mature brain-derived neurotrophic factor (mBDNF expressions caused by scopolamine administration were attenuated by treatment with Gagam-Palmultang. This treatment also promoted neuronal cell proliferation in the hippocampus. Gagam-Palmultang has beneficial effects against scopolamine-induced memory impairments, which are exerted via modulation of the cholinergic system as well as the PI3K and ERK/CREB/BDNF signaling pathway. Therefore, this multiherb formula may be a useful therapeutic agent for diseases associated with memory impairments.

  16. Maternal administration of melatonin prevents spatial learning and memory deficits induced by developmental ethanol and lead co-exposure.

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    Soleimani, Elham; Goudarzi, Iran; Abrari, Kataneh; Lashkarbolouki, Taghi

    2017-05-01

    Melatonin is a radical scavenger with the ability to remove reactive oxidant species. There is report that co-exposure to lead and ethanol during developmental stages induces learning and memory deficits and oxidative stress. Here, we studied the effect of melatonin, with strong antioxidant properties, on memory deficits induced by lead and ethanol co-exposure and oxidative stress in hippocampus. Pregnant rats in lead and ethanol co-exposure group received lead acetate of 0.2% in distilled drinking water and ethanol (4g/kg) by oral gavages once daily from the 5th day of gestation until weaning. Rats received 10mg/kg melatonin by oral gavages. On postnatal days (PD) 30, rats trained with six trials per day for 6 consecutive days in the water maze. On day 37, a probe test was done and oxidative stress markers in the hippocampus were evaluated. Results demonstrated lead and ethanol co-exposed rats exhibited higher escape latency during training trials and reduced time spent in target quadrant, higher escape location latency in probe trial test and had significantly higher malondialdehyde (MDA) levels, significantly lower superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities in the hippocampus. Melatonin treatment could improve memory deficits, antioxidants activity and reduced MDA levels in the hippocampus. We conclude, co-exposure to lead and ethanol impair memory and melatonin can prevent from it by oxidative stress modulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway.

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    Rei, Damien; Mason, Xenos; Seo, Jinsoo; Gräff, Johannes; Rudenko, Andrii; Wang, Jun; Rueda, Richard; Siegert, Sandra; Cho, Sukhee; Canter, Rebecca G; Mungenast, Alison E; Deisseroth, Karl; Tsai, Li-Huei

    2015-06-09

    Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memory-related genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation.

  18. Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway

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    Rei, Damien; Mason, Xenos; Seo, Jinsoo; Gräff, Johannes; Rudenko, Andrii; Wang, Jun; Rueda, Richard; Siegert, Sandra; Cho, Sukhee; Canter, Rebecca G.; Mungenast, Alison E.; Deisseroth, Karl; Tsai, Li-Huei

    2015-01-01

    Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memory-related genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation. PMID:25995364

  19. Physical exercise prevents short and long-term deficits on aversive and recognition memory and attenuates brain oxidative damage induced by maternal deprivation.

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    Neves, Ben-Hur; Menezes, Jefferson; Souza, Mauren Assis; Mello-Carpes, Pâmela B

    2015-12-01

    It is known from previous research that physical exercise prevents long-term memory deficits induced by maternal deprivation in rats. But we could not assume similar effects of physical exercise on short-term memory, as short- and long-term memories are known to result from some different memory consolidation processes. Here we demonstrated that, in addition to long-term memory deficit, the short-term memory deficit resultant from maternal deprivation in object recognition and aversive memory tasks is also prevented by physical exercise. Additionally, one of the mechanisms by which the physical exercise influences the memory processes involves its effects attenuating the oxidative damage in the maternal deprived rats' hippocampus and prefrontal cortex.

  20. Electrical stimulation of prelymbic with different currents intensities on morphine induced spatial memory deficit in rats.

    Science.gov (United States)

    Mehdipour, Shima; Alaei, Hojjatallah; Reisi, Parham; Marghmaleki, Vajihe Saedi

    2016-01-01

    The medial prefrontal cortex (mPFC) is a part of brain reward system involved in cognitive functions such as learning and memory. Previous studies showed that electrical stimulation of prelymbic produced different effects on morphine-induced condition place preference. In this study, we investigated the electrical stimulation with different current intensities on spatial memory in rats. In this study, male Wister rats weighing approximately 200-300 g were used. The effect of prelymbic electrical stimulation with 25 and 150 μA currents intensities in healthy and addicted rats on spatial memory was studied. Spatial memory was investigated using the Morris water maze test in addicted rats after 9 days of electrical stimulation. Our findings have shown that morphine reduces the memory and learning, whereas the present results indicated that electrical stimulation of prelymbic area with current intensity of the 25 μA shortened the time and distance to reach to platform that indicated improvement in spatial memory on addicted rats. Whereas the electrical stimulation of prelymbic area with the current intensity of 150 μA has special weakening effects on spatial memory and prolongs the time and distance to reach the platform. The electrical stimulations of prelymbic with 25 μA current intensity improved the spatial memory in addicted rats while with 150 μA current intensity weakened spatial memory in rats. It is possible that increase in the release of some neurotransmitters reverses the effect of morphine on spatial memory.

  1. The effect of left frontal transcranial direct-current stimulation on propranolol-induced fear memory acquisition and consolidation deficits.

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    Nasehi, Mohammad; Khani-Abyaneh, Mozhgan; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

    2017-07-28

    Accumulating evidence supports the efficacy of transcranial direct current stimulation (tDCS) in modulating numerous cognitive functions. Despite the fact that tDCS has been used for the enhancement of memory and cognition, very few animal studies have addressed its impact on the modulation of fear memory. This study was designed to determine whether pre/post-training frontal tDCS application would alter fear memory acquisition and/or consolidation deficits induced by propranolol in NMRI mice. Results indicated that administration of β1-adrenoceptor blocker propranolol (0.1mg/kg) impaired fear memory retrieval. Pre/post-training application of anodal tDCS when propranolol was administered prior to training reversed contextual memory retrieval whereas only the anodal application prior to training could induce the same result in the auditory test. Meanwhile, anodal stimulation had no effect on fear memories by itself. Moreover, regardless of when cathode was applied and propranolol administered, their combination restored contextual memory retrieval, while only cathodal stimulation prior to training facilitated the contextual memory retrieval. Also, auditory memory retrieval was restored when cathodal stimulation and propranolol occurred prior to training but it was abolished when stimulation occurred after training and propranolol was administered prior to training. Collectively, our findings show that tDCS applied on the left frontal cortex of mice affects fear memory performance. This alteration seems to be task-dependent and varies depending on the nature and timing of the stimulation. In certain conditions, tDCS reverses the effect of propranolol. These results provide initial evidence to support the timely use of tDCS for the modulation of fear-related memories. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Ameliorative effect of lithium chloride on working and spatial memory deficit in a PTZ-induced seizure model

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    Marzieh Yazdani

    2017-06-01

    Full Text Available Background: The repetitive seizure attacks lead to widespread neuronal damage and cognitive deficit, e.g. memory and learning impairment. The single or repeated administration of pentylenetetrazole (PTZ can induce seizure in rat. This study evaluates the neuroprotective effect of lithium chloride (LiCl on PTZ-induced working and spatial memory deficit. Materials and Methods: To induce the PTZ-kindling model, repeated doses of PTZ (40mg/kg/BW/ip were injected for 5 consecutive days. After observing five stages of seizure, the PTZ+Li20, PTZ+Li40 and PTZ+Li80 groups received 20, 40 and 80 mg/kg/BW of LiCl, respectively and the PTZ+Saline group, received Saline for 14 days. The Morris water maze (MWM and Y maze tests were conducted in order to investigate the spatial and working memory. Results: Compared to Control group, the PTZ+Saline group showed a decrease in alteration behavior in Y maze and an increase in latency time and distance to hidden platform in MWM. LiCl-treated rats, especially in the lowest dose, showed a significant higher alteration behavior in Y maze and the lower latency time and distance to hidden platform in MWM than the PTZ+Saline group. Conclusion: The neuroprotective effects of LiCl can ameliorate the spatial and working memory impairment in a PTZ-kindling model.

  3. Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats.

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    Ren, Qing-Guo; Wang, Yan-Juan; Gong, Wei-Gang; Xu, Lin; Zhang, Zhi-Jun

    2015-01-01

    Here, we investigated the effect of escitalopram pretreatment on protein kinase A (PKA)-induced tau hyperphosphorylation and spatial memory deficits in rats using western blot and behavioral tests, respectively. We demonstrated that escitalopram effectively ameliorated tau hyperphosphorylation and the spatial memory deficits induced by PKA activation. We measured the total and activity-dependent Ser9-phosphorylated levels of glycogen synthase kinase (GSK)-3β in hippocampal extracts. No significant change in the total level of GSK-3β was observed between the different groups. However, compared with forskolin injection alone, pretreatment with escitalopram increased the level of Ser9-phosphorylated GSK-3β. We also demonstrated that escitalopram increased Akt phosphorylation at Ser473 (the active form of Akt). Furthermore, we identified other important kinases and phosphatases, such as protein phosphatase 2A, extracellular signal-regulated kinases 1 and 2, and MAP kinase kinase-1/2, that have previously been reported to play a crucial role in tau phosphorylation; however, we did not detect any significant change in the activation of these kinases or phosphatases in our study. We unexpectedly demonstrated that forskolin caused anxiety-like behavior in rats, and pretreatment with escitalopram did not significantly ameliorate the anxiety-like behavior induced by forskolin. These data provide the first evidence that escitalopram ameliorates forskolin-induced tau hyperphosphorylation and spatial memory impairment in rats; these effects do not occur via the anti-anxiety activity of escitalopram but may involve the Akt/GSK-3β signaling pathway.

  4. Tokishakuyakusan ameliorates spatial memory deficits induced by ovariectomy combined with β-amyloid in rats

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    Nobuaki Egashira

    2018-03-01

    Full Text Available Previously, we reported that ovariectomy (OVX combined with β-amyloid peptide (Aβ impaired spatial memory by decreasing extracellular acetylcholine (ACh levels in the dorsal hippocampus. Here, we investigated the effect of tokishakuyakusan (TSS, a Kampo medicine, on the impairment of spatial memory induced by OVX combined with Aβ in rats. Repeated administration of TSS (300 mg/kg, p.o. significantly decreased the number of errors in the eight-arm radial maze test. Though TSS had no effect on extracellular ACh levels at baseline, TSS significantly increased extracellular ACh levels in the dorsal hippocampus. These results suggest that TSS improves the impairment of spatial memory induced by OVX combined with Aβ by (at least in part increasing extracellular ACh levels in the dorsal hippocampus. Keywords: Tokishakuyakusan, Ovariectomy, β-Amyloid, Memory, Acetylcholine

  5. Piracetam prevents memory deficit induced by postnatal propofol exposure in mice.

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    Wang, Yuan-Lin; Li, Feng; Chen, Xin

    2016-05-15

    Postnatal propofol exposure impairs hippocampal synaptic development and memory. However, the effective agent to alleviate the impairments was not verified. In this study, piracetam, a positive allosteric modulator of AMPA receptor was administered following a seven-day propofol regime. Two months after propofol administration, hippocampal long-term potentiation (LTP) and long-term memory decreased, while intraperitoneal injection of piracetam at doses of 100mg/kg and 50mg/kg following last propofol exposure reversed the impairments of memory and LTP. Mechanically, piracetam reversed propofol exposure-induced decrease of BDNF and phosphorylation of mTor. Similar as piracetam, BDNF supplementary also ameliorated propofol-induced abnormalities of synaptic plasticity-related protein expressions, hippocampal LTP and long-term memory. These results suggest that piracetam prevents detrimental effects of propofol, likely via activating BDNF synthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Critical role of CA1 muscarinic receptors on memory acquisition deficit induced by total (TSD) and REM sleep deprivation (RSD).

    Science.gov (United States)

    Javad-Moosavi, Bibi-Zahra; Vaezi, Gholamhassan; Nasehi, Mohammad; Haeri-Rouhani, Seyed-Ali; Zarrindast, Mohammad-Reza

    2017-10-03

    Despite different theories regarding sleep physiological function, an overall census indicates that sleep is useful for neural plasticity which eventually strengthens cognition and brain performance. Different studies show that sleep deprivation (SD) leads to impaired learning and hippocampus dependent memory. According to some studies, cholinergic system plays an important role in sleep (particularly REM sleep), learning, memory, and its retrieval. So this study has been designed to investigate the effect of CA1 Cholinergic Muscarinic Receptors on memory acquisition deficit induced by total sleep deprivation (TSD) and REM sleep deprivation (RSD). A modified water box (locomotor activity may be provide a limiting factor in this method of SD) or multiple platforms were used for induction of TSD or RSD, respectively. Inhibitory passive avoidance apparatus has been used to determine the effects of SD and its changes by physostigmine (as cholinesterase inhibitor) or scopolamine (muscarinic receptor antagonist) on memory formation. Because locomotor activity and pain perception induce critical roles in passive avoidance memory formation, we also measured these factors by open field and hot-plate instruments, respectively. The results showed that TSD and RSD for 24 hours impaired memory formation but they did not alter locomotor activity. TSD also induced analgesia effect, but RSD did not alter it. Intra-CA1 injection of physostigmine (0.0001μg/rat) and scopolamine (0.01μg/rat) did not alter memory acquisition in the sham-TSD or sham-RSD, by themselves. Moreover, intra-CA1 injection of sub-threshold dose of physostigmine (0.0001μg/rat) and scopolamine (0.01μg/rat) could restore the memory acquisition deficit induced by RSD, while scopolamine could restore TSD-induced amnesia. Both drugs reversed analgesia induced by TSD. None of previous interventions altered locomotor activity. According to this study, CA1 cholinergic muscarinic receptors play an important role in

  7. Inflammatory markers are associated with inhibitory avoidance memory deficit induced by sleep deprivation in rats.

    Science.gov (United States)

    Esumi, L A; Palma, B D; Gomes, V L; Tufik, S; Hipólide, D C

    2011-08-01

    Sleep deprivation (SD) causes detrimental effects to the body, such as memory impairment and weight loss. SD also changes the concentration of inflammatory mediators such as cytokines, which, in turn, can affect cognitive functioning. Thus, the objective of this study was to investigate the involvement of these inflammatory mediators in inhibitory avoidance memory deficit in sleep-deprived rats. Male Wistar rats were deprived of sleep by the modified multiple platform method for 96 h, while their respective controls remained in their housing cages. To assess memory after SD, all animals underwent training, followed by the inhibitory avoidance task test 24h later. Also, the weight of each animal was recorded daily. In the first experiment, animals received an acute administration of lipopolysaccharide (LPS, 50 or 75 μg/kg i.p.) 3h before the inhibitory avoidance training. In the experiment 2, the animals received acute or chronic administration of anti-IL-6 antibody (Ab, 2 μg/kg i.p.). The acute administration was performed 3h before the inhibitory avoidance training, while the chronic treatment administrations were performed daily during the SD period. The 75 μg/kg dose of LPS, but not the 50 μg/kg dose, caused a significant attenuation of memory impairment in the sleep-deprived animals. Although the treatments with the anti-IL-6 Ab did not produce any significant changes in cognitive performance, the Ab attenuated weight loss in sleep-deprived animals. Taken together, these results suggest the involvement of inflammatory mediators in the modulation of memory deficit and weight loss that are observed in sleep-deprived rats. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Attenuation of stress induced memory deficits by nonsteroidal anti-inflammatory drugs (NSAIDs) in rats: Role of antioxidant enzymes.

    Science.gov (United States)

    Emad, Shaista; Qadeer, Sara; Sadaf, Sana; Batool, Zehra; Haider, Saida; Perveen, Tahira

    2017-04-01

    Repeated stress paradigms have been shown to cause devastating alterations on memory functions. Stress is linked with inflammation. Psychological and certain physical stressors could lead to neuroinflammation. Inflammatory process may occur by release of mediators and stimulate the production of prostaglandins through cyclooxygenase (COX). Treatment with COX inhibitors, which restrain prostaglandin production, has enhanced memory in a number of neuroinflammatory states showing a potential function for raised prostaglandins in these memory shortfalls. In the present study, potential therapeutic effects of indomethacin and diclofenac sodium on memory in both unrestraint and restraint rats were observed. Two components, long term memory and short term memory were examined by Morris water maze (MWM) and elevated plus maze (EPM) respectively. The present study also demonstrated the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on lipid peroxidation (LPO) and activities of antioxidant enzymes along with the activity of acetylcholinesterase (AChE). Results of MWM and EPM showed significant effects of drugs in both unrestraint and restraint rats as escape latency and transfer latency, in respective behavioral models were decreased as compared to that of control. This study also showed NSAIDs administration decreased LPO and increased antioxidant enzymes activity and decreased AChE activity in rats exposed to repeated stress. In conclusion this study suggests a therapeutic potential of indomethacin and diclofenac against repeated stress-induced memory deficits. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  9. Inhibitory Effects of Eucommia ulmoides Oliv. Bark on Scopolamine-Induced Learning and Memory Deficits in Mice.

    Science.gov (United States)

    Kwon, Seung-Hwan; Ma, Shi-Xun; Joo, Hyun-Joong; Lee, Seok-Yong; Jang, Choon-Gon

    2013-11-01

    Eucommia ulmoides Oliv. Bark (EUE) is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia as well as to promote longevity. In this study, we tested the effects of EUE aqueous extract in graded doses to protect and enhance cognition in scopolamine-induced learning and memory impairments in mice. EUE significantly improved the impairment of short-term or working memory induced by scopolamine in the Y-maze and significantly reversed learning and memory deficits in mice as measured by the passive avoidance and Morris water maze tests. One day after the last trial session of the Morris water maze test (probe trial session), EUE dramatically increased the latency time in the target quadrant in a dose-dependent manner. Furthermore, EUE significantly inhibited acetylcholinesterase (AChE) and thiobarbituric acid reactive substance (TBARS) activities in the hippocampus and frontal cortex in a dose-dependent manner. EUE also markedly increased brain-derived neurotrophic factor (BDNF) and phosphorylation of cAMP element binding protein (CREB) in the hippocampus of scopolamine-induced mice. Based on these findings, we suggest that EUE may be useful for the treatment of cognitive deficits, and that the beneficial effects of EUE are mediated, in part, by cholinergic signaling enhancement and/or protection.

  10. Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity, anxiety, and memory deficits.

    Science.gov (United States)

    Bhagya, Venkanna Rao; Srikumar, Bettadapura N; Veena, Jayagopalan; Shankaranarayana Rao, Byrathnahalli S

    2017-08-01

    Exposure to prolonged stress results in structural and functional alterations in the hippocampus including reduced long-term potentiation (LTP), neurogenesis, spatial learning and working memory impairments, and enhanced anxiety-like behavior. On the other hand, enriched environment (EE) has beneficial effects on hippocampal structure and function, such as improved memory, increased hippocampal neurogenesis, and progressive synaptic plasticity. It is unclear whether exposure to short-term EE for 10 days can overcome restraint stress-induced cognitive deficits and impaired hippocampal plasticity. Consequently, the present study explored the beneficial effects of short-term EE on chronic stress-induced impaired LTP, working memory, and anxiety-like behavior. Male Wistar rats were subjected to chronic restraint stress (6 hr/day) over a period of 21 days, and then they were exposed to EE (6 hr/day) for 10 days. Restraint stress reduced hippocampal CA1-LTP, increased anxiety-like symptoms in elevated plus maze, and impaired working memory in T-maze task. Remarkably, EE facilitated hippocampal LTP, improved working memory performance, and completely overcame the effect of chronic stress on anxiety behavior. In conclusion, exposure to EE can bring out positive effects on synaptic plasticity in the hippocampus and thereby elicit its beneficial effects on cognitive functions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Scutellaria barbata flavonoids alleviate memory deficits and neuronal injuries induced by composited Aβ in rats.

    Science.gov (United States)

    Wu, Xiao G; Wang, Shu S; Miao, Hong; Cheng, Jian J; Zhang, Shu F; Shang, Ya Z

    2016-12-08

    The aim of the present study was to investigate the effects of Scutellaria barbata flavonoids (SBF) on memory impairment and neuronal injury induced by amyloid beta protein 25-35 in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1 (RHTGF-β1) (composited Aβ) in rats. The composited Aβ-treated model of Alzheimer's disease (AD)-like memory impairment and neuronal injury was established in male rats by right intracerebroventricular injection of composited Aβ, and the effects of SBF were assessed using this rat model. Spatial learning and memory of rats were assessed in the Morris water maze, and neuronal injury was assessed by light and electron microscopy with hematoxylin-eosin or uranyl acetate and lead nitrate-sodium citrate staining, respectively. In the Morris water maze, memory impairment was observed in 94.7% of the composited Aβ-treated rats. The composited Aβ-treated rats took longer than sham-operated rats to find the hidden platform during position navigation and reversal learning trials. They also spent less time swimming in the target quadrant in the probe trial. Optical and electron microscopic observations showed significant neuropathological changes including neuron loss or pyknosis in hippocampus, typical colliquative necrosis in cerebral cortex, mitochondrial swelling and cristae fragmentation and a large number of lipofuscin deposits in the cytoplasm. Treatment with SBF (35-140 mg/kg) reduced the memory impairment and neuronal injury induced by composited Aβ. SBF-mediated improvement of composited Aβ-induced memory impairment and neuronal injury in rats provides an appropriate rationale for evaluating SBF as a promising agent for treatment of AD.

  12. Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease.

    Science.gov (United States)

    Soodi, Maliheh; Saeidnia, Soodabeh; Sharifzadeh, Mohammad; Hajimehdipoor, Homa; Dashti, Abolfazl; Sepand, Mohammad Reza; Moradi, Shahla

    2016-04-01

    Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer's disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD.

  13. Ameliorative effect of Asparagus racemosus root extract against pentylenetetrazol-induced kindling and associated depression and memory deficit.

    Science.gov (United States)

    Pahwa, Priyanka; Goel, Rajesh Kumar

    2016-04-01

    Asparagus racemosus (A. racemosus) roots are extensively used in traditional medicine for the management of epilepsy. The aim of the present study was to investigate the ameliorative effect of A. racemosus root extract (ARE) against pentylenetetrazol-induced kindling and associated depression and memory deficit. Kindling was successfully induced by repeated administration of a subconvulsant dose of PTZ (35 mg/kg; i.p.) at an interval of 48 ± 2 h in 43 days (21 injections). Pretreatment with valproate (300 mg/kg; i.p.), a major antiepileptic drug as well as ARE significantly suppressed the progression of kindling. Moreover, ARE also ameliorated the kindling-associated depression and memory deficit as indicated by decreased immobility time and increased step-down latency, respectively, as compared to vehicle control animals. Further, these behavioral observations were complemented with analogous neurochemical changes. In conclusion, the results of the present study showed that ARE treatment has an ameliorative effect against PTZ-induced kindling and associated behavioral comorbidities. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Role of α7nAChR-NMDAR in sevoflurane-induced memory deficits in the developing rat hippocampus.

    Directory of Open Access Journals (Sweden)

    XiaoHong Tang

    Full Text Available Detrimental effects of volatile anaesthetics, including sevoflurane, on the structure and function of the developing brain have been reported. The internalization of N-methyl-D-aspartate receptors (NMDARs contributes to anaesthetic neurotoxicity. Both nicotinic acetylcholine receptors (nAChRs and NMDAR play a critical role in the development of the nervous system. Moreover, nAChR can interact with NMDAR, and previous studies have demonstrated modulation of NMDAR by nAChR. In our study, we used an α7 nicotinic acetylcholine receptor (α7nAChR agonist and α7nAChR antagonist to explore the role of α7nAChR and NMDAR in sevoflurane-induced long-term effects on memory and dendritic spine both in vivo and in vitro. The results revealed that the activation of α7nAChR attenuated the development of sevoflurane-induced memory deficit and dendritic spine changes, which might be by regulating NR2B-containing NMDAR trafficking from the intracellular pool to the cell surface pool in the hippocampus. Moreover, we demonstrated that α7nAChR could regulate NR2B-containing NMDAR via Src-family tyrosine kinase (SFK. Thus, our current study indicates that the trafficking of NR2B-containing NMDAR is regulated by α7nAChR via SFK in neonatal rat hippocampus, which may be secondary to sevoflurane-induced cognitive deficits in the developing hippocampus.

  15. Piperphentonamine (PPTA) attenuated cerebral ischemia-induced memory deficits via neuroprotection associated with anti-apoptotic activity.

    Science.gov (United States)

    Bin, Juan; Wang, Qian; Zhuo, Ye-Ye; Xu, Jiang-Ping; Zhang, Han-Ting

    2012-12-01

    The calcium sensitizers levosimendan and piperphentonamine hydrochloride (PPTA) are used as cardiovascular drugs for treatment of heart failure. Given that levosimendan has been reported to exhibit a neuroprotective profile in a model of traumatic brain injury, it was interesting to know whether PPTA, a new calcium sensitizer recently developed in China, exerts a similar effect. The objective of this study was to determine whether PPTA exhibited neuroprotective effects and whether these properties were associated with memory. Four-vessel occlusion (4-VO) was used to induce global cerebral ischemia/reperfusion injury in rats treated with or without PPTA (5, 10 mg/kg, i.p., 2 h after the onset of reperfusion and then once a day for 15 consecutive days). Memory was measured using the step-through passive avoidance test. Neurochemical changes were examined in rat PC12 cells treated with oxygen-glucose deprivation (OGD) for 4 h followed by reoxygenation (OGD-R) for 24 h, in the absence or presence of PPTA. In vehicle-treated animals, 4-VO for 10 min produced memory deficits, as demonstrated by decreased retention in step-through passive avoidance, and massive neuron loss in the hippocampal CA1 subregion. These effects were attenuated by PPTA. The results were consistent with those observed in PC12 cells. PPTA treatment increased cell viability, as indicated by MTT assay, inhibited apoptosis, and decreased extracellular lactate dehydrogenase levels in Na(2)S(2)O(4)-treated PC12 cells. These results provide novel demonstration for the ability of PPTA to attenuate cerebral ischemia-induced memory deficits via neuroprotection in the hippocampus. The neuroprotective effect of PPTA appears to be associated with its anti-apoptotic activity. PPTA has the therapeutic potential for ischemic stroke.

  16. Rutin protects against neuronal damage in vitro and ameliorates doxorubicin-induced memory deficits in vivo in Wistar rats

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    Ramalingayya GV

    2017-03-01

    Full Text Available Grandhi Venkata Ramalingayya, Sri Pragnya Cheruku, Pawan G Nayak, Anoop Kishore, Rekha Shenoy, Chamallamudi Mallikarjuna Rao, Nandakumar Krishnadas Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India Abstract: Doxorubicin (DOX is the most widely used broad-spectrum anticancer agent, either alone or in combination, for most cancers including breast cancer. Long-term use of chemotherapeutic agents to treat breast cancer patients results in cognitive complications with a negative impact on survivors’ quality of life. The study objective was to evaluate rutin (RUT for its neuroprotective effect against DOX in human neuroblastoma (IMR32 cells in vitro and study its potential to ameliorate DOX-induced cognitive dysfunction in Wistar rats. Cell viability assay (3-[4,5 dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide, neurite growth assay, detection of apoptosis by (acridine orange/ethidium bromide staining, intracellular reactive oxygen species (ROS assay, and flowcytometric analysis were carried out to assess neuroprotective potential against DOX. An in vivo study was conducted for assessing protective effect of RUT against memory deficit associated with DOX-induced chemobrain using object recognition task (ORT. Locomotion was assessed using open field test. Serum biochemistry, acetylcholinesterase, oxidative stress markers in hippocampus, and frontal cortex were assessed. Histopathological analysis of major organ systems was also carried out. Prior exposure to RUT at 100 µM protected IMR32 cells from DOX (1 µM neurotoxicity. DOX exposure resulted in increased cellular death, apoptosis, and intracellular ROS generation with inhibition of neurite growth in differentiated IMR32 cells, which was significantly ameliorated by RUT. Cognitive dysfunction was induced in Wistar rats by administering ten cycles of DOX (2.5 mg/kg, intraperitoneal, once in 5 days, as we observed

  17. The effect of long term administration of ascorbic acid on the learning and memory deficits induced by diabetes in rat

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    Parisa Hasanein

    2010-04-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Ascorbic acid improves cognitive impairments in several experimental models. Diabetes causes learning and memory deficits. In this study we hypothesized that chronic treatment with ascorbic acid (100mg/kg, p.o would affect on the passive avoidance learning (PAL and memory in control and streptozocin-induced diabetic rats."n"nMethods: Diabetes was induced by a single i.p. injection of STZ (60mg/kg. The rats were considered diabetic if plasma glucose levels exceeded 250mg/dl on three days after STZ injection. Treatment was begun at the onset of hyperglycemia. PAL was assessed 30 days later. Retention test was done 24 h after training. At the end, animals were weighted and blood samples were drawn for plasma glucose measurement."n"nResults: Diabetes caused impairment in acquisition and retrieval processes of PAL and memory in rats. Ascorbic acid treatment improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. Ascorbic acid administration also improved the body weight loss and hyperglycemia of diabetics. Hypoglycemic and antioxidant properties of the vitamin may be involved in the memory improving effects of such treatment."n"nConclusion: These results show that

  18. Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze

    Directory of Open Access Journals (Sweden)

    Veronica eSebastian

    2013-05-01

    Full Text Available Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within in a single task. Thus we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM with a sequence of 4 baited and 4 unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test two weeks after training. Multiple training trials not only provide robust training, but also test the subjects’ ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing two weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI.

  19. Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze.

    Science.gov (United States)

    Sebastian, Veronica; Diallo, Aissatou; Ling, Douglas S F; Serrano, Peter A

    2013-01-01

    Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI) results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within a single task. Thus, we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM) with a sequence of four baited and four unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test 2 weeks after training. Multiple training trials not only provide robust training, but also test the subjects' ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing 2 weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI.

  20. Rivastigmine treatment for the prevention of electroconvulsive therapy-induced memory deficits in patients with schizophrenia.

    Science.gov (United States)

    Stryjer, Rafael; Ophir, Dana; Bar, Faina; Spivak, Baruch; Weizman, Abraham; Strous, Rael D

    2012-01-01

    Electroconvulsive therapy (ECT) is an effective strategy in some treatment-resistant patients with schizophrenia. However, ECT is associated with cognitive adverse effects, most notably, memory loss. This study examined the effects of rivastigmine, a selective central nervous system acetylcholinesterase inhibitor, with benefits on cognition in Alzheimer disease, on memory performance in patients with schizophrenia treated with ECT. Thirty inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision schizophrenia treated with ECT were coadministered rivastigmine (3-4.5 mg/d) or placebo in a prospective, randomized, double-blind, placebo-controlled trial (maximum period of 4 weeks). Over the ECT course, scores on the cognitive subscale of the Alzheimer's Disease Assessment in subjects receiving placebo showed no significant change, whereas subjects receiving rivastigmine displayed decreased cognitive subscale of the Alzheimer's Disease Assessment scores, indicating cognitive improvement (P ECT and indicate possible beneficial effects of rivastigmine coadministration in minimizing some of these ECT-induced cognitive impairments.

  1. The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze.

    Science.gov (United States)

    Hosseini, Mahmoud; Hadjzadeh, Mosa Al-Reza; Derakhshan, Mohammad; Havakhah, Shahrzad; Rassouli, Fatemeh Behnam; Rakhshandeh, Hassan; Saffarzadeh, Fatema

    2010-03-01

    Functional consequences of hypothyroidism include impaired learning and memory and inability to produce long-term potentiation (LTP) in hippocampus. Olibanum has been used for variety of therapeutic purposes. In traditional medicine, oilbanum is used to enhance learning and memory. In the present study the effect of olibanum on memory deficit in hypothyroid rats was investigated. Male wistar rats were divided into four groups and treated for 180 days. Group 1 received tap drinking water while in group 2, 0.03% methimazol was added to drinking water. Group 3 and 4 were treated with 0.03% methimazole as well as 100 and 500 mg/kg olibanum respectively. The animals were tested in Morris water maze. The swimming speed was significantly lower and the distance and time latency were higher in group 2 compared with group 1. In groups 3 and 4 the swimming speed was significantly higher while, the length of the swim path and time latency were significantly lower in comparison with group 2. It is concluded that methimazole-induced hypothyroidism impairs learning and memory in adult rats which could be prevented by using olibanum.

  2. Modafinil prevents inhibitory avoidance memory deficit induced by sleep deprivation in rats.

    Science.gov (United States)

    Moreira, Karin Monteiro; Ferreira, Tatiana Lima; Hipolide, Debora Cristina; Fornari, Raquel Vecchio; Tufik, Sergio; Oliveira, Maria Gabriela Menezes

    2010-07-01

    Evaluation of modafinil effects on the inhibitory avoidance task (IA). Rats were trained on a multiple trial IA task after receiving modafinil or vehicle injections. In experiment 1 they were trained with a weak protocol under baseline condition and in experiment 2, with a stronger protocol under sleep-deprivation condition. In experiment 1 modafinil improved rats' acquisition whereas the retention test remained unaffected. In Experiment 2 modafinil did not interfere with training performance, but the lower dose prevented the retention impairment in sleep-deprived animals. Modafinil is able to improve acquisition in normal rats and reverse the long-term memory impairment induced by sleep-deprivation.

  3. Viral-mediated Zif268 expression in the prefrontal cortex protects against gonadectomy-induced working memory, long-term memory, and social interaction deficits in male rats.

    Science.gov (United States)

    Dossat, Amanda M; Jourdi, Hussam; Wright, Katherine N; Strong, Caroline E; Sarkar, Ambalika; Kabbaj, Mohamed

    2017-01-06

    In humans, some males experience reductions in testosterone levels, as a natural consequence of aging or in the clinical condition termed hypogonadism, which are associated with impaired cognitive performance and mood disorder(s). Some of these behavioral deficits can be reversed by testosterone treatment. Our previous work in rats reported that sex differences in the expression of the transcription factor Zif268, a downstream target of testosterone, within the medial prefrontal cortex (mPFC) mediates sex differences in social interaction. In the present study, we aimed to examine the effects of gonadectomy (GNX) in male rats on mPFC Zif268 expression, mood and cognitive behaviors. We also examined whether reinstitution of Zif268 in GNX rats will correct some of the behavioral deficits observed following GNX. Our results show that GNX induced a downregulation of Zif268 protein in the mPFC, which was concomitant with impaired memory in the y-maze and spontaneous object recognition test, reduced social interaction time, and depression-like behaviors in the forced swim test. Reinstitution of mPFC Zif268, using a novel adeno-associated-viral (AAV) construct, abrogated GNX-induced working memory and long-term memory impairments, and reductions in social interaction time, but not GNX-induced depression-like behaviors. These findings suggest that mPFC Zif268 exerts beneficial effects on memory and social interaction, and could be a potential target for novel treatments for behavioral impairments observed in hypogonadal and aged men with declining levels of gonadal hormones. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Reversal of scopolamine-induced spatial and recognition memory deficits in mice by novel multifunctional dimers bis-cognitins.

    Science.gov (United States)

    Han, Ren-wen; Zhang, Rui-san; Chang, Min; Peng, Ya-li; Wang, Pei; Hu, Sheng-quan; Choi, Chung-lit; Yin, Ming; Wang, Rui; Han, Yi-fan

    2012-08-27

    Our previous reports indicated that bis(propyl)-cognitin (B3C) and bis(heptyl)-cognitin (B7C), as novel dimers derived from tacrine, may be potential multifunctional drugs for treating Alzheimer's disease. There is little knowledge on the cognitive function of B3C while B7C appeared to reverse learning and memory impairments. In this study, for the first time, we evaluated the anti-amnesic effects of B3C and B7C on learning and memory deficits induced by scopolamine using both Morris water maze and novel object recognition tasks in mice. Under the same experimental condition, the anti-amnesic effect of tacrine was also compared. Briefly, in both tasks, scopolamine (0.1-0.6 mg/kg, ip) dose-dependently impaired learning and memory functions. B3C (1.5-2.5 μmol/kg), B7C (0.4-0.6 μmol/kg) or tacrine (8-12 μmol/kg), each administered ip, dose-dependently mitigated scopolamine-induced learning and memory impairments in both tasks. Our present results show, for the first time, that B3C and B7C reverse cognitive impairment resulted from scopolamine in both water maze and object recognition tasks; and under the same condition, the relative potency of B3C and B7C to improve cognitive capacity was 5-20 folds over that of tacrine. These novel in vivo findings further demonstrate that both B3C and B7C may potentially be developed as Alzheimer's therapeutic drugs for different severities of neurodegenerations. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Caffeic acid attenuates oxidative stress, learning and memory deficit in intra-cerebroventricular streptozotocin induced experimental dementia in rats.

    Science.gov (United States)

    Deshmukh, Rahul; Kaundal, Madhu; Bansal, Vikas; Samardeep

    2016-07-01

    Oxidative stress has been implicated in cognitive decline as seen during normal aging and in sporadic Alzheimer's disease (AD). Caffeic acid, a polyphenolic compound, has been reported to possess potent antioxidant and neuroprotective properties. The role of caffeic acid in experimental dementia is not fully understood. Thus the present study was designed to investigate the therapeutic potential of caffeic acid in streptozotocin (STZ)-induced experimental dementia of Alzheimer's type in rats. Streptozotocin (STZ) was administered intracerebroventrically (ICV) on day 1 and 3 (3mg/kg, ICV bilaterally) in Wistar rats. Caffeic acid was administered (10, 20 and 40mg/kg/day p.o.) 1h following STZ infusion upto 21st day. Morris water maze and object recognition task were used to assess learning and memory in rats. Terminally, acetylcholinesterase (AChE) activity and the levels of oxido-nitrosative stress markers were determined in cortical and hippocampal brain regions of rats. STZ produced significant (plearning and memory impairment, oxido-nitrosative stress and cholinergic deficit in rats. Whereas, caffeic acid treatment significantly (p<0.001) and dose dependently attenuated STZ induced behavioral and biochemical abnormalities in rats. The observed cognitive improvement following caffeic acid in STZ treated rats may be due to its antioxidant activity and restoration of cholinergic functions. Our results suggest the therapeutic potential of caffeic acid in cognitive disorders such as AD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Cannabidiol attenuates deficits of visuospatial associative memory induced by Δ9tetrahydrocannabinol

    Science.gov (United States)

    Wright, M Jerry; Vandewater, Sophia A; Taffe, Michael A

    2013-01-01

    BACKGROUND AND PURPOSE Recent human studies suggest that recreational cannabis strains that are relatively high in cannabidiol (CBD) content produce less cognitive impairment than do strains with negligible CBD and similar Δ9tetrahydrocannabinol (THC) content. Self-selection in such studies means it is impossible to rule out additional variables which may determine both cannabis strain selection and basal cognitive performance level. Controlled laboratory studies can better determine a direct relationship. EXPERIMENTAL APPROACH In this study, adult male rhesus monkeys were assessed on visuospatial Paired Associates Learning and Self-Ordered Spatial Search memory tasks, as well as additional tests of motivation and manual dexterity. Subjects were challenged with THC (0.2, 0.5 mg·kg−1, i.m.) in randomized order and evaluated in the presence or absence of 0.5 mg·kg−1 CBD. KEY RESULTS CBD attenuated the effects of THC on paired associates learning and a bimanual motor task without affecting the detrimental effects of THC on a Self-Ordered Spatial Search task of working memory. CBD did not significantly reverse THC-induced impairment of a progressive ratio or a rotating turntable task. CONCLUSIONS AND IMPLICATIONS This study provides direct evidence that CBD can oppose the cognitive-impairing effects of THC and that it does so in a task-selective manner when administered simultaneously in a 1:1 ratio with THC. The addition of CBD to THC-containing therapeutic products may therefore help to ameliorate unwanted cognitive side-effects. LINKED ARTICLE This article is commented on by Mechoulam and Parker, pp 1363–1364 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12400 PMID:23550724

  7. Cannabidiol attenuates deficits of visuospatial associative memory induced by Δ(9) tetrahydrocannabinol.

    Science.gov (United States)

    Wright, M Jerry; Vandewater, Sophia A; Taffe, Michael A

    2013-12-01

    Recent human studies suggest that recreational cannabis strains that are relatively high in cannabidiol (CBD) content produce less cognitive impairment than do strains with negligible CBD and similar Δ(9) tetrahydrocannabinol (THC) content. Self-selection in such studies means it is impossible to rule out additional variables which may determine both cannabis strain selection and basal cognitive performance level. Controlled laboratory studies can better determine a direct relationship. In this study, adult male rhesus monkeys were assessed on visuospatial Paired Associates Learning and Self-Ordered Spatial Search memory tasks, as well as additional tests of motivation and manual dexterity. Subjects were challenged with THC (0.2, 0.5 mg·kg(-1) , i.m.) in randomized order and evaluated in the presence or absence of 0.5 mg·kg(-1) CBD. CBD attenuated the effects of THC on paired associates learning and a bimanual motor task without affecting the detrimental effects of THC on a Self-Ordered Spatial Search task of working memory. CBD did not significantly reverse THC-induced impairment of a progressive ratio or a rotating turntable task. This study provides direct evidence that CBD can oppose the cognitive-impairing effects of THC and that it does so in a task-selective manner when administered simultaneously in a 1:1 ratio with THC. The addition of CBD to THC-containing therapeutic products may therefore help to ameliorate unwanted cognitive side-effects. This article is commented on by Mechoulam and Parker, pp 1363-1364 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12400. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

  8. Learning and memory deficits in male adult mice treated with a benzodiazepine sleep-inducing drug during the juvenile period

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    Yusuke Furukawa

    2016-07-01

    Full Text Available Gamma-aminobutyric acid (GABA, the major inhibitory neurotransmitter in the mammalian central nervous system, is also known to be important for brain development. Therefore, disturbances of GABA receptor (GABA-R mediated signaling (GABA-R signal during brain development may influence normal brain maturation and cause late-onset brain malfunctions. In this study, we examined whether the temporal stimulation of the GABA-R signal during brain development induces late-onset adverse effects on the brain in adult male mice. To stimulate the GABA-R signal, we used either the benzodiazepine sleep-inducing drug triazolam (TZ or the non-benzodiazepine drug zolpidem (ZP. We detected deficits in learning and memory in mice treated with TZ during the juvenile period, as seen in the fear conditioning test. On the other hand, ZP administration during the juvenile period had little effect. In addition, decreased protein expression of GluR1 and GluR4, which are excitatory neurotransmitter receptors, was detected in the hippocampi of mice treated with TZ during the juvenile period. We measured mRNA expression of the immediate early genes (IEGs, which are neuronal activity markers, in the hippocampus shortly after the administration of TZ or ZP to juvenile mice. Decreased IEG expression was detected in mice with juvenile TZ administration, but not in mice with juvenile ZP administration. Our findings demonstrate that TZ administration during the juvenile period can induce irreversible brain dysfunction in adult mice. It may need to take an extra care for the prescription of benzodiazepine sleep-inducing drugs to juveniles because it might cause late onset learning and memory defects.

  9. Involvement of dopaminergic and cholinergic systems in social isolation-induced deficits in social affiliation and conditional fear memory in mice.

    Science.gov (United States)

    Okada, R; Fujiwara, H; Mizuki, D; Araki, R; Yabe, T; Matsumoto, K

    2015-07-23

    Post-weaning social isolation rearing (SI) in rodents elicits various behavioral abnormalities including attention deficit hyperactivity disorder-like behaviors. In order to obtain a better understanding of SI-induced behavioral abnormalities, we herein investigated the effects of SI on social affiliation and conditioned fear memory as well as the neuronal mechanism(s) underlying these effects. Four-week-old male mice were group-housed (GH) or socially isolated for 2-4 weeks before the experiments. The social affiliation test and fear memory conditioning were conducted at the age of 6 and 7 weeks, respectively. SI mice were systemically administered saline or test drugs 30 min before the social affiliation test and fear memory conditioning. Contextual and auditory fear memories were elucidated 1 and 4 days after fear conditioning. Social affiliation and contextual and auditory fear memories were weaker in SI mice than in GH mice. Methylphenidate (MPH), an inhibitor for dopamine transporters, ameliorated the SI-induced social affiliation deficit and the effect was attenuated by SCH23390, a D1 receptor antagonist, but not by sulpiride, a D2 receptor antagonist. On the other hand, tacrine, an acetylcholinesterase inhibitor, had no effect on this deficit. In contrast, tacrine improved SI-induced deficits in fear memories in a manner that was reversed by the muscarinic receptor antagonist scopolamine, while MPH had no effect on memory deficits. Neurochemical studies revealed that SI down-regulated the expression levels of the phosphorylated forms of neuro-signaling proteins, calmodulin-dependent kinase II (p-CaMKII), and cyclic AMP-responsive element binding protein (p-CREB), as well as early growth response protein-1 (Egr-1) in the hippocampus. The administration of MPH or tacrine before fear conditioning had no effect on the levels of the phosphorylated forms of the neuro-signaling proteins elucidated following completion of the auditory fear memory test; however

  10. Tualang Honey Attenuates Noise Stress-Induced Memory Deficits in Aged Rats.

    Science.gov (United States)

    Azman, Khairunnuur Fairuz; Zakaria, Rahimah; Abdul Aziz, Che Badariah; Othman, Zahiruddin

    2016-01-01

    Ageing and stress exposure may lead to memory impairment while oxidative stress is thought to be one of the underlying mechanisms involved. This study aimed to investigate the potential protective effects of Tualang honey supplementation on memory performance in aged rats exposed to noise stress. Tualang honey supplementation was given orally, 200 mg/kg body weight for 28 days. Rats in the stress group were subjected to loud noise, 100 dB(A), 4 hours daily for 14 days. All rats were subjected to novel object recognition test for evaluation of memory performance. It was observed that the rats subjected to noise stress exhibited significantly lower memory performance and higher oxidative stress as evident by elevated malondialdehyde and protein carbonyl levels and reduction of antioxidant enzymes activities compared to the nonstressed rats. Tualang honey supplementation was able to improve memory performance, decrease oxidative stress levels, increase brain-derived neurotrophic factor (BDNF) concentration, decrease acetylcholinesterase activity, and enhance neuronal proliferation in the medial prefrontal cortex (mPFC) and hippocampus. In conclusion, Tualang honey protects against memory decline due to stress exposure and/or ageing via enhancement of mPFC and hippocampal morphology possibly secondary to reduction in brain oxidative stress and/or upregulation of BDNF concentration and cholinergic system.

  11. Novel 5-HT5A receptor antagonists ameliorate scopolamine-induced working memory deficit in mice and reference memory impairment in aged rats

    Directory of Open Access Journals (Sweden)

    Mayako Yamazaki

    2015-03-01

    Full Text Available Despite the human 5-HT5A receptor being cloned in 1994, the biological function of this receptor has not been extensively characterized due to a lack of specific ligands. We recently reported that the selective 5-HT5A receptor antagonist ASP5736 ameliorated cognitive impairment in several animal models of schizophrenia. Given that areas of the brain with high levels of 5-HT5A receptor expression, such as the hippocampus and cerebral cortex, have important functions in cognition and memory, we evaluated the chemically diverse, potent and brain-penetrating 5-HT5A receptor antagonists ASP5736, AS2030680, and AS2674723 in rodent models of cognitive dysfunction associated with dementia. Each of these compounds exhibited a high affinity for recombinant 5-HT5A receptors that was comparable to that of the non-selective ligand of this receptor, lysergic acid diethylamide (LSD. Although each compound had a low affinity for other receptors, 5-HT5A was the only receptor for which all three compounds had a high affinity. Each of the three compounds ameliorated scopolamine-induced working memory deficit in mice and improved reference memory impairment in aged rats at similar doses. Further, ASP5736 decreased the binding of LSD to 5-HT5A receptors in the olfactory bulb of rats in a dose-dependent manner and occupied 15%–50% of brain 5-HT5A receptors at behaviorally effective doses. These results indicate that the 5-HT5A receptor is involved in learning and memory and that treatment with 5-HT5A receptor antagonists might be broadly effective for cognitive impairment associated with not only schizophrenia but also dementia.

  12. Novel 5-HT5A receptor antagonists ameliorate scopolamine-induced working memory deficit in mice and reference memory impairment in aged rats.

    Science.gov (United States)

    Yamazaki, Mayako; Okabe, Mayuko; Yamamoto, Noriyuki; Yarimizu, Junko; Harada, Katsuya

    2015-03-01

    Despite the human 5-HT5A receptor being cloned in 1994, the biological function of this receptor has not been extensively characterized due to a lack of specific ligands. We recently reported that the selective 5-HT5A receptor antagonist ASP5736 ameliorated cognitive impairment in several animal models of schizophrenia. Given that areas of the brain with high levels of 5-HT5A receptor expression, such as the hippocampus and cerebral cortex, have important functions in cognition and memory, we evaluated the chemically diverse, potent and brain-penetrating 5-HT5A receptor antagonists ASP5736, AS2030680, and AS2674723 in rodent models of cognitive dysfunction associated with dementia. Each of these compounds exhibited a high affinity for recombinant 5-HT5A receptors that was comparable to that of the non-selective ligand of this receptor, lysergic acid diethylamide (LSD). Although each compound had a low affinity for other receptors, 5-HT5A was the only receptor for which all three compounds had a high affinity. Each of the three compounds ameliorated scopolamine-induced working memory deficit in mice and improved reference memory impairment in aged rats at similar doses. Further, ASP5736 decreased the binding of LSD to 5-HT5A receptors in the olfactory bulb of rats in a dose-dependent manner and occupied 15%-50% of brain 5-HT5A receptors at behaviorally effective doses. These results indicate that the 5-HT5A receptor is involved in learning and memory and that treatment with 5-HT5A receptor antagonists might be broadly effective for cognitive impairment associated with not only schizophrenia but also dementia. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  13. Protective effect of resveratrol against chronic intermittent hypoxia-induced spatial memory deficits, hippocampal oxidative DNA damage and increased p47Phox NADPH oxidase expression in young rats.

    Science.gov (United States)

    Abdel-Wahab, Basel A; Abdel-Wahab, Mahmoud M

    2016-05-15

    Long-term intermittent hypoxia (IH) is a characteristic hallmark of obstructive sleep apnea (OSA) and causes most of the neurological aspects of OSA, such as spatial memory and learning deficits. These deficits are accompanied by an increase in oxidative stress and inflammation in brain areas involved in cognition, such as the hippocampus, particularly in children. Resveratrol is a natural polyphenolic compound with potent antioxidant, anti-inflammatory and neuroprotective properties. The aim of this work is to study the possible protective effect of resveratrol against IH-induced neurobehavioral deficits and to investigate the possible mechanism of this protective effect in the young rat model of OSA. The effect of resveratrol (5 and 10mg/kg, orally) on anxiety, spatial memory and learning deficits in young rats exposed to IH for 6 weeks and the corresponding biochemical changes were studied. Resveratrol attenuated IH-induced anxiety and spatial memory deficits, as indicated by the elevated plus maze and Morris water maze tests, respectively, in a dose-dependent manner. In addition, resveratrol antagonized IH-induced increases in hippocampal glutamate, TBARS and 8-OHdG levels and p47Phox expression and decreases in GSH levels and GSH-Px activity in the hippocampus of IH-exposed young rats. Resveratrol ameliorates IH-induced anxiety and spatial learning deficits through multiple beneficial effects on hippocampal oxidative pathways that involve decreased expression of the p47Phox subunit of NADPH oxidase. Hence, the potential therapeutic role of resveratrol in OSA may be utilized in the near future and deserves further exploration. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Critical Role of Endoplasmic Reticulum Stress in Chronic Intermittent Hypoxia-Induced Deficits in Synaptic Plasticity and Long-Term Memory.

    Science.gov (United States)

    Xu, Lin-Hao; Xie, Hui; Shi, Zhi-Hui; Du, Li-Da; Wing, Yun-Kwok; Li, Albert M; Ke, Ya; Yung, Wing-Ho

    2015-09-20

    This study examined the role of endoplasmic reticulum (ER) stress in mediating chronic intermittent hypoxia (IH)-induced neurocognitive deficits. We designed experiments to demonstrate that ER stress is initiated in the hippocampus under chronic IH and determined its role in apoptotic cell death, impaired synaptic structure and plasticity, and memory deficits. Two weeks of IH disrupted ER fine structure and upregulated ER stress markers, glucose-regulated protein 78, caspase-12, and C/EBP homologous protein, in the hippocampus, which could be suppressed by ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid. Meanwhile, ER stress induced apoptosis via decreased Bcl-2, promoted reactive oxygen species production, and increased malondialdehyde formation and protein carbonyl, as well as suppressed mitochondrial function. These effects were largely prevented by ER stress inhibitors. On the other hand, suppression of oxidative stress could reduce ER stress. In addition, the length of the synaptic active zone and number of mature spines were reduced by IH. Long-term recognition memory and spatial memory were also impaired, which was accompanied by reduced long-term potentiation in the Schaffer collateral pathway. These effects were prevented by coadministration of the TUDCA. These results show that ER stress plays a critical role in underlying memory deficits in obstructive sleep apnea (OSA)-associated IH. Attenuators of ER stress may serve as novel adjunct therapeutic agents for ameliorating OSA-induced neurocognitive impairment.

  15. N-methyl-D-aspartate prevented memory deficits induced by MK-801 in mice

    Czech Academy of Sciences Publication Activity Database

    Hliňák, Zdeněk; Krejčí, I.

    2003-01-01

    Roč. 52, č. 6 (2003), s. 809-812 ISSN 0862-8408 R&D Projects: GA ČR GA309/00/1644 Institutional research plan: CEZ:AV0Z5011922 Keywords : N-methyl-D-aspartate * MK-801 * spatial memory Subject RIV: FH - Neurology Impact factor: 0.939, year: 2003

  16. The effect of CA1 α2 adrenergic receptors on memory retention deficit induced by total sleep deprivation and the reversal of circadian rhythm in a rat model.

    Science.gov (United States)

    Norozpour, Yaser; Nasehi, Mohammad; Sabouri-Khanghah, Vahid; Torabi-Nami, Mohammad; Zarrindast, Mohammad-Reza

    2016-09-01

    The α2 adrenergic receptors which abundantly express in the CA1 region of the hippocampus play an important role in the regulation of sleep and memory retention processes. Based on the available evidence, the aim of our study was to investigate consequences of the activation and deactivation of CA1 α2 adrenergic receptors (by clonidine and yohimbine, respectively) on the impairment of memory retention induced by total sleep deprivation (TSD) and the reversal of circadian rhythm (RCR) in a rat model. To this end, the water box apparatus and passive avoidance task were in turn used to induce sleep deprivation and assess memory retention. Our findings suggested that TSD (for 24 and 36, but not 12h) and RCR (12h/day for 3 consecutive days) impair memory function. The post-training intra-CA1 administration of yohimbine (α2 adrenergic receptor antagonist) on its own, at the dose of 0.1μg/rat, decreased the step-through latency and locomotor activity in the TSD- sham treated but not undisturbed sleep rats. Unlike yohimbine, clonidine (α2 adrenergic receptor agonist), in all applied doses (0.001, 0.01 and 0.1μg/rat), failed to induce such an effect. While the subthreshold dose of yohimbine (0.001μg/rat) abrogated the impairment of memory retention induced by the 24-h TSD, it could potentiate the impairment of memory retention induced by 36-h TSD, suggesting the modulatory effect of yohimbine. Moreover, the subthreshold dose of clonidine (0.1μg/rat) restored the memory retention deficit in TSD rats (24 and 36h). On the other hand, the subthreshold dose of clonidine (0.1μg/rat), but not yohimbine (0.001μg/rat) restored the memory retention deficit in RCR rats. Such interventions however did not alter the locomotor activity. The above observations proposed that CA1 α2 adrenergic receptors play a potential role in memory retention deficits induced by TSD and RCR. Copyright © 2016. Published by Elsevier Inc.

  17. Curcumin Improves Amyloid β-Peptide (1-42) Induced Spatial Memory Deficits through BDNF-ERK Signaling Pathway.

    Science.gov (United States)

    Zhang, Lu; Fang, Yu; Xu, Yuming; Lian, Yajun; Xie, Nanchang; Wu, Tianwen; Zhang, Haifeng; Sun, Limin; Zhang, Ruifang; Wang, Zhenhua

    2015-01-01

    Curcumin, the most active component of turmeric, has various beneficial properties, such as antioxidant, anti-inflammatory, and antitumor effects. Previous studies have suggested that curcumin reduces the levels of amyloid and oxidized proteins and prevents memory deficits and thus is beneficial to patients with Alzheimer's disease (AD). However, the molecular mechanisms underlying curcumin's effect on cognitive functions are not well-understood. In the present study, we examined the working memory and spatial reference memory in rats that received a ventricular injection of amyloid-β1-42 (Aβ1-42), representing a rodent model of Alzheimer's disease (AD). The rats treated with Aβ1-42 exhibited obvious cognitive deficits in behavioral tasks. Chronic (seven consecutive days, once per day) but not acute (once a day) curcumin treatments (50, 100, and 200 mg/kg) improved the cognitive functions in a dose-dependent manner. In addition, the beneficial effect of curcumin is accompanied by increased BDNF levels and elevated levels of phosphorylated ERK in the hippocampus. Furthermore, the cognition enhancement effect of curcumin could be mimicked by the overexpression of BDNF in the hippocampus and blocked by either bilateral hippocampal injections with lentiviruses that express BDNF shRNA or a microinjection of ERK inhibitor. These findings suggest that chronic curcumin ameliorates AD-related cognitive deficits and that upregulated BDNF-ERK signaling in the hippocampus may underlie the cognitive improvement produced by curcumin.

  18. Extended Remediation of Sleep Deprived-Induced Working Memory Deficits Using fMRI-guided Transcranial Magnetic Stimulation

    Science.gov (United States)

    Luber, Bruce; Steffener, Jason; Tucker, Adrienne; Habeck, Christian; Peterchev, Angel V.; Deng, Zhi-De; Basner, Robert C.; Stern, Yaakov; Lisanby, Sarah H.

    2013-01-01

    Study Objectives: We attempted to prevent the development of working memory (WM) impairments caused by sleep deprivation using fMRI-guided repetitive transcranial magnetic stimulation (rTMS). Novel aspects of our fMRI-guided rTMS paradigm included the use of sophisticated covariance methods to identify functional networks in imaging data, and the use of fMRI-targeted rTMS concurrent with task performance to modulate plasticity effects over a longer term. Design: Between-groups mixed model. Setting: TMS, MRI, and sleep laboratory study. Participants: 27 subjects (13 receiving Active rTMS, and 14 Sham) completed the sleep deprivation protocol, with another 21 (10 Active, 11 Sham) non-sleep deprived subjects run in a second experiment. Interventions: Our previous covariance analysis had identified a network, including occipital cortex, which demonstrated individual differences in resilience to the deleterious effects of sleep deprivation on WM performance. Five Hz rTMS was applied to left lateral occipital cortex while subjects performed a WM task during 4 sessions over the course of 2 days of total sleep deprivation. Measurements and Results: At the end of the sleep deprivation period, Sham sleep deprived subjects exhibited degraded performance in the WM task. In contrast, those receiving Active rTMS did not show the slowing and lapsing typical in sleep deprivation, and instead performed similarly to non- sleep deprived subjects. Importantly, the Active sleep deprivation group showed rTMS-induced facilitation of WM performance a full 18 hours after the last rTMS session. Conclusions: Over the course of sleep deprivation, these results indicate that rTMS applied concurrently with WM task performance affected neural circuitry involved in WM to prevent its full impact. Citation: Luber B; Steffener J; Tucker A; Habeck C; Peterchev AV; Deng ZD; Basner RC; Stern Y; Lisanby SH. Extended remediation of sleep deprived-induced working memory deficits using f

  19. Different Role of CA1 5HT3 Serotonin Receptors on Memory Acquisition Deficit Induced by Total (TSD) and REM Sleep Deprivation (RSD).

    Science.gov (United States)

    Eydipour, Zainab; Vaezi, Gholamhassan; Nasehi, Mohammad; Haeri-Rouhani, Seyed-Ali; Zarrindast, Mohammad-Reza

    2017-09-01

    Serotonin receptors such as 5-HT3 plays critical role in regulation of sleep, wake cycle and cognitive process. Thus, we investigated the role of CA1 5HT3 serotonin receptors in memory acquisition deficit induced by total sleep deprivation (TSD; for 24 hour) and REM sleep deprivation (RSD; for 24 hour). Pain perception and locomotor activity were also assessed as factors that may affect the memory process. Modified water box and multi-platform apparatus were used to induce TSD or RSD, respectively. Passive avoidance, hot plate and open field devices were used for assessment of memory acquisition, pain and locomotor activity, respectively. Totally, 152 male Wistar rats were used in the study. Pre-training, intra-CA1 injection of 5-HT3 receptor agonist Chlorophenylbiguanide (Mchl; 0.01 and 0.001 µg/rat; P memory acquisition and did not alter pain response, while higher dose of both drugs increased locomotor activity in normal rats. Both TSD and RSD reduced memory acquisition (P effect. The amnesia induced by TSD was restored by subthreshold dose of Y25130 (0.001 µg/rat; P effect (P memory acquisition deficit and increased locomotor activity (P < 0.001 for Mchl and P < 0.01 for Y25130), while the Y25130 (P < 0.001), but not Mchl induced analgesia in the RSD rats. Based on the above data, CA1 5HT3 receptors seem to play a critical role in cognitive and non-cognitive behaviors induced by TSD and RSD.

  20. Minocycline ameliorates D-galactose-induced memory deficits and loss of Arc/Arg3.1 expression.

    Science.gov (United States)

    Li, Xu; Lu, Fen; Li, Wei; Xu, Jun; Sun, Xiao-Jing; Qin, Ling-Zhi; Zhang, Qian-Lin; Yao, Yong; Yu, Qing-Kai; Liang, Xin-Liang

    2016-10-01

    Dysfunction of learning and memory is widely found in many neurological diseases. Understanding how to preserve the normal function of learning and memory will be extremely beneficial for the treatment of these diseases. However, the possible protective effect of minocycline in memory impairment is unknown. We used the well-established D-galactose rat amnesia model and two behavioral tasks, the Morris water maze and the step-down task, for memory evaluation. Western blot and PCR were used to examine the protein and mRNA levels of Arc/Arg3.1. We report that minocycline supplementation ameliorates both the spatial and fear memory deficits caused by D-galactose. We also found that Arc/Arg3.1, c-fos, and brain-derived neurotrophic factor levels are decreased in the D-galactose animal model, and that minocycline reverses the protein and mRNA levels of Arc in the hippocampus, suggesting the potential role of Arc/Arg3.1 in minocycline's neuroprotective mechanism. Our study strongly suggests that minocycline can be used as a novel treatment for memory impairment in neurological diseases.

  1. The Histamine H3 Receptor Antagonist E159 Reverses Memory Deficits Induced by Dizocilpine in Passive Avoidance and Novel Object Recognition Paradigm in Rats

    Directory of Open Access Journals (Sweden)

    Alaa Alachkar

    2017-10-01

    Full Text Available The involvement of histamine H3 receptors (H3Rs in memory is well known, and the potential of H3R antagonists in therapeutic management of neuropsychiatric diseases, e.g., Alzheimer disease (AD is well established. Therefore, the effects of histamine H3 receptor (H3R antagonist E159 (2.5–10 mg/kg, i.p. in adult male rats on dizocilpine (DIZ-induced memory deficits were studied in passive avoidance paradigm (PAP and in novel object recognition (NOR using pitolisant (PIT and donepezil (DOZ as standard drugs. Upon acute systemic pretreatment of E159 at three different doses, namely 2.5, 5, and 10 mg/kg, i.p., 2.5 and 5 but not 10 mg/kg of E159 counteracted the DIZ (0.1 mg-induced memory deficits, and this E159 (2.5 mg-elicited memory-improving effects in DIZ-induced amnesic model were moderately abrogated after acute systemic administration of scopolamine (SCO, H2R antagonist zolantidine (ZOL, but not with H1R antagonist pyrilamine to the animals. Moreover, the observed memory-enhancing effects of E159 (2.5 mg/kg, i.p. were strongly abrogated when animals were administered with a combination of SCO and ZOL. Furthermore, the E159 (2.5 mg-provided significant memory-improving effect of in DIZ-induced short-term memory (STM impairment in NOR was comparable to the DOZ-provided memory-enhancing effect, and was abolished when animals were injected with the CNS-penetrant histamine H3R agonist R-(α-methylhistamine (RAMH. However, E159 at a dose of 2.5 mg/kg failed to exhibit procognitive effect on DIZ-induced long-term memory (LTM in NOR. Furthermore, the results observed revealed that E159 (2.5 mg/kg did not alter anxiety levels and locomotor activity of animals naive to elevated-plus maze (EPM, demonstrating that improved performances with E159 (2.5 mg/kg in PAP or NOR are unrelated to changes in emotional responding or in spontaneous locomotor activity. These results provide evidence for the potential of drugs targeting H3Rs for the treatment of

  2. Preventive Effect of Liothyronine on Electroconvulsive Therapy-Induced Memory Deficit in Patients with Major Depressive Disorder: A Double-Blind Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Arash Mohagheghi

    2015-01-01

    Full Text Available Introduction and Objective. Despite the effectiveness of electroconvulsive therapy (ECT in treating major depressive disorder (MDD, its cognitive side effects make it less popular. This study investigated the impact of liothyronine on ECT-induced memory deficit in patients with MDD. Methodology. This is a double-blind clinical trial, in which 60 patients with MDD who were referred for ECT were selected. The diagnosis was based on the criteria of DSM-IV-TR. Patients were divided randomly into two groups to receive either liothyronine (50 mcg every morning or placebo. After the assessment with Wechsler Memory Scale-Revised (WMS-R before first session of ECT, posttests were repeated again, two months after the completion of ECT. Findings. By controlling the pretest scores, the mean scores of the experimental group were higher than the control group in delayed recall, verbal memory, visual memory, general memory, and attention/concentration scales (P<0.05. Conclusion. Liothyronine may prevent ECT-induced memory impairment in patients with MDD. This study has been registered in IRCT under IRCT201401122660N2.

  3. Verapamil enhances acute stress or glucocorticoid-induced deficits in retrieval of long-term memory in rats.

    Science.gov (United States)

    Rashidy-Pour, Ali; Vafaei, Abbas Ali; Taherian, Abbas Ali; Miladi-Gorji, Hossein; Sadeghi, Hassan; Fathollahi, Yaghoub; Bandegi, Ahmad Reza

    2009-10-12

    This study was designed to investigate an interaction between acute restraint stress and corticosterone with verapamil, a blocker of L-type voltage-dependent calcium (VDC) channels on retrieval of long-term memory. Young adult male rats were trained in one trial inhibitory avoidance task (0.5 mA, 3 s footshock). On retention test given 48 h after training, the latency to re-enter dark compartment of the apparatus was recorded. In Experiment 1, verapamil pretreatment (5, 10, or 20 mg/kg) enhanced the impairing effects of acute stress (which was applied for 10 min in a Plexiglass tube 30 min before the retention test) on memory retrieval. The applied stress increased circulating corticosterone levels as assessed immediately after the retention test, indicating that stress-induced impairment of memory retrieval is mediated, in part, by increased plasma levels of glucocorticoids. Verapamil did not change this response. In Experiment 2, pretreatment of an intermediate dose of verapamil also enhanced corticosterone-induced impairment of memory retrieval. In Experiments 3 and 4, acute stress or corticosterone did not change motor activity with or without prior treatment of verapamil, suggesting that stress or glucocorticoid-induced impairment of memory retrieval is not due to any gross disturbances in motor performance of animals. These findings indicate that blockade of L-type VDC channels enhances stress or glucocorticoid-induced impairment of memory retrieval, and provide evidence for the existence of an interaction between glucocorticoids and L-type VDC channels on memory retrieval.

  4. Chronic ethanol exposure during adolescence through early adulthood in female rats induces emotional and memory deficits associated with morphological and molecular alterations in hippocampus.

    Science.gov (United States)

    Oliveira, Ana Ca; Pereira, Maria Cs; Santana, Luana N da Silva; Fernandes, Rafael M; Teixeira, Francisco B; Oliveira, Gedeão B; Fernandes, Luanna Mp; Fontes-Júnior, Enéas A; Prediger, Rui D; Crespo-López, Maria E; Gomes-Leal, Walace; Lima, Rafael R; Maia, Cristiane do Socorro Ferraz

    2015-06-01

    There is increasing evidence that heavy ethanol exposure in early life may produce long-lasting neurobehavioral consequences, since brain structural maturation continues until adolescence. It is well established that females are more susceptible to alcohol-induced neurotoxicity and that ethanol consumption is increasing among women, especially during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence through early adulthood in female rats may induce hippocampal histological damage and neurobehavioral impairments. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) by gavage from the 35(th)-90(th) day of life. Ethanol-exposed animals displayed reduced exploration of the central area and increased number of fecal boluses in the open field test indicative of anxiogenic responses. Moreover, chronic high ethanol exposure during adolescence induced marked impairments on short-term memory of female rats addressed on social recognition and step-down inhibitory avoidance tasks. These neurobehavioral deficits induced by ethanol exposure during adolescence through early adulthood were accompanied by the reduction of hippocampal formation volume as well as the loss of neurons, astrocytes and microglia cells in the hippocampus. These results indicate that chronic high ethanol exposure during adolescence through early adulthood in female rats induces long-lasting emotional and memory deficits associated with morphological and molecular alterations in the hippocampus. © The Author(s) 2015.

  5. Mice Lacking the β4 Subunit of the Nicotinic Acetylcholine Receptor Show Memory Deficits, Altered Anxiety- and Depression-Like Behavior, and Diminished Nicotine-Induced Analgesia

    Science.gov (United States)

    Semenova, Svetlana; Contet, Candice; Roberts, Amanda J.

    2012-01-01

    Rationale: The role of β4-containing nicotinic acetylcholine receptors (nAChRs) in cognition, anxiety, depression, and analgesia in the absence of nicotine is unclear. Methods: Wild-type (β4+/+) and knockout (β4−/−) mice for the nAChR β4 subunit were tested in behavioral tests assessing cognitive function, affective behaviors, and nociception. Results: There were no learning and memory deficits in β4−/− mice compared with β4+/+ mice during the acquisition of the Barnes maze, contextual fear conditioning, and Y maze tasks. In the Barnes maze memory retention test, male β4−/− mice showed reduced use of the spatial search strategy, indicating small spatial memory deficits compared with β4+/+ mice. In the cue-induced fear conditioning memory retention test, β4−/− mice exhibited reduced freezing time compared with β4+/+ mice. Compared with β4+/+ mice, β4−/− mice exhibited decreased anxiety-like behavior in the light–dark box. Depression-like behavior in β4−/− mice was decreased in the tail suspension test and increased in the forced swim test compared with β4+/+ mice. β4−/− mice did not differ from β4+/+ mice in basal nociception but were less sensitive to the antinociceptive effect of nicotine in 2 tests of acute thermal pain. Conclusions: Lack of β4-containing nAChRs resulted in small deficits in hippocampus- and amygdala-dependent memory retention functions. β4-containing nAChRs are involved in anxiety- and depression-like behaviors and contribute to the analgesic effects of nicotine. PMID:22573727

  6. Measuring Working Memory Deficits in Aphasia

    Science.gov (United States)

    Mayer, Jamie F.; Murray, Laura L.

    2012-01-01

    Purpose: Many adults with aphasia demonstrate concomitant deficits in working memory (WM), but such deficits are difficult to quantify because of a lack of validated measures as well as the complex interdependence between language and WM. We examined the feasibility, reliability, and internal consistency of an "n"-back task for…

  7. N-acetyl-L-tryptophan, a substance-P receptor antagonist attenuates aluminum-induced spatial memory deficit in rats.

    Science.gov (United States)

    Fernandes, Joylee; Mudgal, Jayesh; Rao, Chamallamudi Mallikarjuna; Arora, Devinder; Basu Mallik, Sanchari; Pai, K S R; Nampoothiri, Madhavan

    2018-06-01

    Neuroinflammation plays an important role in the pathophysiology of Alzheimer's disease. Neurokinin substance P is a key mediator which modulates neuroinflammation through neurokinin receptor. Involvement of substance P in Alzheimer's disease is still plausible and various controversies exist in this hypothesis. Preventing the deleterious effects of substance P using N-acetyl-L-tryptophan, a substance P antagonist could be a promising therapeutic strategy. This study was aimed to evaluate the effect of N-acetyl-L-tryptophan on aluminum induced spatial memory alterations in rats. Memory impairment was induced using aluminum chloride (AlCl 3 ) at a dose of 10 mg/kg for 42 d. After induction of dementia, rats were exposed to 30 and 50 mg/kg of N-acetyl-L-tryptophan for 28 d. Spatial memory alterations were measured using Morris water maze. Acetylcholinesterase activity and antioxidant enzyme glutathione level were assessed in hippocampus, frontal cortex and striatum. The higher dose of N-acetyl-L-tryptophan (50 mg/kg) significantly improved the aluminum induced memory alterations. N-acetyl-L-tryptophan exposure resulted in significant increase in acetylcholinesterase activity and glutathione level in hippocampus. The neuroprotective effect of N-acetyl-L-tryptophan could be due to its ability to block substance P mediated neuroinflammation, reduction in oxidative stress and anti-apoptotic properties. To conclude, N-acetyl-L-tryptophan may be considered as a novel neuroprotective therapy in Alzheimer's disease.

  8. [Neuroleptic induced deficit syndrome].

    Science.gov (United States)

    Szafrański, T

    1995-01-01

    Increasing interest in subjective aspects of therapy and rehabilitation focused the attention of psychiatrists, psychologists and psychopharmacologists on the mental side effects of neuroleptics. For the drug-related impairment of affective, cognitive and social function the name of neuroleptic-induced deficit syndrome (NIDS) is proposed. Patients with NIDS appear to be indifferent to the environmental stimuli, retarded and apathetic. They complain of feeling drugged and drowsy, weird, they suffer from lack of motivation, feel like "zombies". The paper presents description of NIDS and its differentiation from negative and depressive symptoms in schizophrenia and subjective perceiving of extrapyramidal syndromes.

  9. Administration of the TrkB receptor agonist 7,8-dihydroxyflavone prevents traumatic stress-induced spatial memory deficits and changes in synaptic plasticity.

    Science.gov (United States)

    Sanz-García, Ancor; Knafo, Shira; Pereda-Pérez, Inmaculada; Esteban, José A; Venero, César; Armario, Antonio

    2016-09-01

    Post-traumatic stress disorder (PTSD) occurs after exposure to traumatic situations and it is characterized by cognitive deficits that include impaired explicit memory. The neurobiological bases of such PTSD-associated memory alterations are yet to be elucidated and no satisfactory treatment for them exists. To address this issue, we first studied whether a single exposure of young adult rats (60 days) to immobilization on boards (IMO), a putative model of PTSD, produces long-term behavioral effects (2-8 days) similar to those found in PTSD patients. Subsequently, we investigated whether the administration of the TrkB agonist 7,8-dihydroxyflavone (DHF) 8 h after stress (therapeutic window) ameliorated the PTSD-like effect of IMO and the associated changes in synaptic plasticity. A single IMO exposure induced a spatial memory impairment similar to that found in other animal models of PTSD or in PTSD patients. IMO also increased spine density and long-term potentiation (LTP) in the CA3-CA1 pathway. Significantly, DHF reverted both spatial memory impairment and the increase in LTP, while it produced no effect in the controls. These data provide novel insights into the possible neurobiological substrate for explicit memory impairment in PTSD patients, supporting the idea that the activation of the BDNF/TrkB pathway fulfils a protective role after severe stress. Administration of DHF in the aftermath of a traumatic experience might be relevant to prevent its long-term consequences. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Modafinil restores methamphetamine induced object-in-place memory deficits in rats independent of glutamate N-methyl d-aspartate receptor expression

    Science.gov (United States)

    Reichel, Carmela M.; Gilstrap, Meghin G.; Ramsey, Lauren A.; See, Ronald E.

    2013-01-01

    Background Chronic methamphetamine (meth) abuse in humans can lead to various cognitive deficits, including memory loss. We previously showed that chronic meth self-administration impairs memory for objects relative to their location and surrounding objects. Here, we demonstrate that the cognitive enhancer, modafinil, reversed this cognitive impairment independent of glutamate N-methyl d-aspartate (GluN) receptor expression. Methods Male, Long-Evans rats underwent a noncontingent (Experiment 1) or contingent (Experiment 2) meth regimen. After one week of abstinence, rats were tested for object-in-place recognition memory. Half the rats received either vehicle or modafinil (100 mg/kg) immediately after object familiarization. Rats (Experiment 2) were sacrificed immediately after the test and brain areas that comprise the key circuitry for object in place performance were manually dissected. Subsequently, glutamate receptor expression was measured from a crude membrane fraction using western blot procedures. Results Saline-treated rats spent more time interacting with the objects in changed locations, while meth-treated rats distributed their time equally among all objects. Meth-treated rats that received modafinil showed a reversal in the deficit, whereby they spent more time exploring the objects in the new locations. GluN2B receptor subtype was decreased in the perirhinal cortex, yet remained unaffected in the prefrontal cortex and hippocampus of meth rats. This meth-induced down regulation occurred whether or not meth experienced rats received vehicle or modafinil. Conclusions These data support the use of modafinil for memory impairment in meth addiction. Further studies are needed to elucidate the neural mechanisms of modafinil reversal of cognitive impairments. PMID:24120858

  11. Study of Melatonin Protective Effects on Learning and Memory Deficits Induced by Administration of Lead during Pregnancy and Postpartum in Rat: Behavioral and Biochemical Evaluations

    Directory of Open Access Journals (Sweden)

    Elham Soleimani

    2016-05-01

    Full Text Available Abstract Background: Few studies have investigated the possible ways to prevent lead induced defects during gestation and lactation. The aim of this study was to investigate the effect of melatonin as a hormone with antioxidant properties on oxidative stress in the hippocampus and learning and memory impairment induced by administration of lead. Materials and Methods: Pregnant rats were exposed to treatments of control, lead acetate (0.2% solution in water, lead acetate + melatonin and melatonin (10 mg / kg by oral gavage from gestation day 6 until weaning. 21 days after birth, the activities of several antioxidant enzymes including superoxide dismutase (SOD, glutathione peroxidase (GPX and catalase (CAT as well as malondialdehyde levels in hippocampus of 23 male offspring rats were assayed. To behavioral studies, on postnatal day 30, 57 rats were trained 6 days in the Morris water maze and the probe test was performed 24 h later. Results: The results showed that administration of lead during pregnancy and lactation could increase MDA levels and decrease glutathione peroxidase, superoxide dismutase and catalase antioxidant enzymes activities in the hippocampus of male offspring. Also, this treatment significantly disrupted performance of the Morris water maze test and impaired learning and spatial memory in male offspring compared with control. Administration of melatonin attenuated lipid peroxidation and could improve learning and spatial memory deficits and the activity of antioxidant enzymes in lead exposure group. Conclusion: Melatonin as a neuropotective drug can protect the hippocampus against the complications of lead exposure, in the course of development.

  12. Pretreatment with 5-hydroxymethyl-2-furaldehyde blocks scopolamine-induced learning deficit in contextual and spatial memory in male mice.

    Science.gov (United States)

    Lee, Younghwan; Gao, Qingtao; Kim, Eunji; Lee, Younghwa; Park, Se Jin; Lee, Hyung Eun; Jang, Dae Sik; Ryu, Jong Hoon

    2015-07-01

    5-Hydroxymethyl-2-furaldehyde (5-HMF) is a compound derived from the dehydration of certain sugars. The aim of the present study was to evaluate the effect of 5-HMF on the cognitive impairment induced by scopolamine, a muscarinic receptor antagonist. To measure various cognitive functions, we conducted the step-through passive avoidance task, the Y-maze task and the Morris water maze task. A single administration of 5-HMF (5 or 10mg/kg, p.o.) significantly attenuates scopolamine-induced cognitive impairment in these behavioral tasks without changes in locomotor activity, and the effect of 5-HMF on scopolamine-induced cognitive impairment was significantly reversed by a sub-effective dose of MK-801, an NMDA receptor antagonist. In addition, a single administration of 5-HMF (10mg/kg, p.o.) enhanced the cognitive performance of normal naïve mice in the passive avoidance task. Furthermore, Western blot analysis revealed that the levels of phosphorylated Ca(2+)/calmodulin-dependent protein kinase II-α (CaMKII) and extracellular signal-regulated kinases (ERK) were significantly enhanced by the single administration of 5-HMF in the hippocampal tissues. Taken together, the present study suggests that 5-HMF may block scopolamine-induced learning deficit and enhance cognitive function via the activation of NMDA receptor signaling, including CaMKII and ERK, and would be an effective candidate against cognitive disorders, such as Alzheimer's disease. Copyright © 2015. Published by Elsevier Inc.

  13. Protective effects of salicylate on PKA inhibitor (H-89)-induced spatial memory deficit via lessening autophagy and apoptosis in rats.

    Science.gov (United States)

    Azimi, Leila; Kachooeian, Maryam; Khodagholi, Fariba; Yans, Asal; Heysieattalab, Soomaayeh; Vakilzadeh, Gelareh; Vosoughi, Nasim; Sanati, Mehdi; Taghizadeh, Ghorban; Sharifzadeh, Mohammad

    In this study, the effects of salicylate on spatial learning and memory, through its effects on autophagy and apoptosis, were evaluated in the presence of the PKA inhibitor H-89. Adult male Wistar rats were divided into experimental groups as follows: salicylate (30, 50, 100μg/0.5μl/side, intra-hippocampal; 400mg/kg, intra-peritoneal), donepezil (1mg/kg as a positive control for behavioral effects of salicylate), H-89 (1μl/side of 5 or 20μM), H-89 plus salicylate and H-89 plus donepezil. The Morris water maze test was used for evaluation of spatial learning and memory. The levels of different apoptotic and autophagic biomarkers were evaluated using the western blot technique. Salicylate (100μg/0.5μl/side) significantly reduced the escape latency on training days, increased the percentage of time spent in the target quadrant during the probe trial and reversed the inhibitory effects of H-89 during the process of spatial learning and memory. The behavioral efficacy of salicylate was comparable to that of donepezil. In addition, salicylate significantly decreased the levels of apoptotic proteins, Bax and caspase 3, and increased the Bcl2 levels in all groups. Furthermore, the levels of LC3II and Atg7 were decreased by salicylate. Our study revealed that both systemic and direct intra-hippocampal administration of salicylate can facilitate the spatial learning and memory. Additionally, intra-hippocampal administration of salicylate can reduce apoptotic and autophagic proteins. The antioxidant activity of salicylate might lead to increased pCREB via stimulation of signaling pathways, resulting in reduction of H-89-induced apoptosis and autophagy. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Protective effects of pre-germinated brown rice diet on low levels of Pb-induced learning and memory deficits in developing rat.

    Science.gov (United States)

    Zhang, Rong; Lu, Hongzhi; Tian, Su; Yin, Jie; Chen, Qing; Ma, Li; Cui, Shijie; Niu, Yujie

    2010-03-30

    Lead (Pb) is a known neurotoxicant in humans and experimental animals. Numerous studies have provided evidence that humans, especially young children, and animals chronically intoxicated with low levels of Pb show learning and memory impairments. Unfortunately, Pb-poisoning cases continue to occur in many countries. Because the current treatment options are very limited, there is a need for alternative methods to attenuate Pb toxicity. In this study, the weaning (postnatal day 21, PND21) rats were randomly divided into five groups: the control group (AIN-93G diet, de-ionized water), the lead acetate (PbAC) group (AIN-93G diet, 2g/L PbAC in de-ionized water), the lead acetate+WR group (white rice diet, 2g/L PbAC in de-ionized water; PbAC+WR), the lead acetate+BR group (brown rice diet, 2g/L PbAC in de-ionized water; PbAC+BR) and the lead acetate+PR group (pre-germinated brown rice diet, 2g/L PbAC in de-ionized water; PbAC+PR). The animals received the different diets until PND60, and then the experiments were terminated. The protective effects of pre-germinated brown rice (PR) on Pb-induced learning and memory impairment in weaning rats were assessed by the Morris water maze and one-trial-learning passive avoidance test. The anti-oxidative effects of feeding a PR diet to Pb-exposed rats were evaluated. The levels of reactive oxygen species (ROS) were determined by flow cytometry. The levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), gamma-aminobutyric acid (GABA) and glutamate were determined by HPLC. Our data showed that feeding a PR diet decreased the accumulation of lead and decreased Pb-induced learning and memory deficits in developing rats. The mechanisms might be related to the anti-oxidative effects and large amount of GABA in PR. Our study provides a regimen to reduce Pb-induced toxicity, especially future learning and memory deficits in the developing brain.

  15. Memory Deficits in Learning Disabled.

    Science.gov (United States)

    Nolan, John D.; Driscoll, Rosemary L.

    Memory storage and retrieval of learning disabled (LD) and normal children at two age levels (8-9 years and 11-12 years) were compared using a multitrial free recall paradigm. Stimuli were two lists of 20 high frequency nouns. Each child was tested individually on both lists on different days; one presentation was blocked, one random with…

  16. Effects of pre-germinated brown rice on beta-amyloid protein-induced learning and memory deficits in mice.

    Science.gov (United States)

    Mamiya, Takayoshi; Asanuma, Takamasa; Kise, Mitsuo; Ito, Yukihiko; Mizukuchi, Aya; Aoto, Hiromichi; Ukai, Makoto

    2004-07-01

    We evaluated the effects of pre-germinated brown rice (hatsuga genmai, PGR) on learning and memory and compared them with those of polished rice or cornstarch. In mice that were fed pellets of polished rice or PGR for two weeks, the learning ability in the Morris water maze test was significantly enhanced compared with mice that were fed cornstarch pellets. In the Y-maze test, the intake of food pellets for two weeks failed to affect spontaneous alternation behavior. Beta-amyloid(25-35) (Abeta(25-35): 3 nmol/mouse, i.c.v.) protein impaired spontaneous alternation behavior in mice that were fed pellets of cornstarch or polished rice. In contrast, PGR pellets prevented the Abeta(25-35)-induced impairment of spontaneous alternation behavior. These results suggest that polished rice and PGR have facilitating effects on spatial learning. In particular, it is surmised that PGR may prevent Alzheimer's disease associated with Abeta.

  17. Continuation of exercise is necessary to inhibit high fat diet-induced β-amyloid deposition and memory deficit in amyloid precursor protein transgenic mice.

    Directory of Open Access Journals (Sweden)

    Masato Maesako

    Full Text Available High fat diet (HFD is prevalent in many modern societies and HFD-induced metabolic condition is a growing concern worldwide. It has been previously reported that HFD clearly worsens cognitive function in amyloid precursor protein (APP transgenic mice. On the other hand, we have demonstrated that voluntary exercise in an enriched environment is an effective intervention to rescue HFD-induced β-amyloid (Aβ deposition and memory deficit. However, it had been unclear whether consumption of HFD after exercising abolished the beneficial effect of exercise on the inhibition of Alzheimer's disease (AD pathology. To examine this question, we exposed wild type (WT and APP mice fed with HFD to exercise conditions at different time periods. In our previous experiment, we gave HFD to mice for 20 weeks and subjected them to exercise during weeks 10-20. In the present study, mice were subjected to exercise conditions during weeks 0-10 or weeks 5-15 while being on HFD. Interestingly, we found that the effect of exercise during weeks 0-10 or weeks 5-15 on memory function was not abolished in WT mice even if they kept having HFD after finishing exercise. However, in APP transgenic mice, HFD clearly disrupted the effect of exercise during weeks 0-10 or weeks 5-15 on memory function. Importantly, we observed that the level of Aβ oligomer was significantly elevated in the APP mice that exercised during weeks 0-10: this might have been caused by the up-regulation of Aβ production. These results provide solid evidence that continuation of exercise is necessary to rescue HFD-induced aggravation of cognitive decline in the pathological setting of AD.

  18. Fermented Sipjeondaebo-tang Alleviates Memory Deficits and Loss of Hippocampal Neurogenesis in Scopolamine-induced Amnesia in Mice.

    Science.gov (United States)

    Park, Hee Ra; Lee, Heeeun; Park, Hwayong; Cho, Won-Kyung; Ma, Jin Yeul

    2016-03-04

    We investigated the anti-amnesic effects of SJ and fermented SJ (FSJ) on scopolamine (SCO)-induced amnesia mouse model. Mice were orally co-treated with SJ or FSJ (125, 250, and 500 mg/kg) and SCO (1 mg/kg), which was injected intraperitoneally for 14 days. SCO decreased the step-through latency and prolonged latency time to find the hidden platform in the passive avoidance test and Morris water maze test, respectively, and both SCO effects were ameliorated by FSJ treatment. FSJ was discovered to promote hippocampal neurogenesis during SCO treatment by increasing proliferation and survival of BrdU-positive cells, immature/mature neurons. In the hippocampus of SCO, oxidative stress and the activity of acetylcholinesterase were elevated, whereas the levels of acetylcholine and choline acetyltransferase were diminished; however, all of these alterations were attenuated by FSJ-treatment. The alterations in brain-derived neurotrophic factor, phosphorylated cAMP response element-binding protein, and phosphorylated Akt that occurred following SCO treatment were protected by FSJ administration. Therefore, our findings are the first to suggest that FSJ may be a promising therapeutic drug for the treatment of amnesia and aging-related or neurodegenerative disease-related memory impairment. Furthermore, the molecular mechanism by which FSJ exerts its effects may involve modulation of the cholinergic system and BDNF/CREB/Akt pathway.

  19. Jealousy delirium associated with memory deficits

    Directory of Open Access Journals (Sweden)

    Orazio Zanetti

    2007-09-01

    Full Text Available Alzheimer’s disease is a progressive and fatal neurodegenerative disorder manifested by cognitive and memory deterioration, progressive impairment of activities of daily living, and a variety of neuropsychiatric symptoms and behavioural disturbances. A correct and early diagnosis not only allows prompt treatment but can also give the person with Alzheimer’s and his family more time to arm themselves with knowledge about this type of dementia and the best way to live with the disease. The role of Family Physician is very important in early diagnosis: dementia may be suspected if memory deficits are exhibited during the medical history and physical examination. Information from the patient’s family members, friends and caregivers may also point to signs of dementia. We report a case of a 75-years-old man who was suffering from cognitive deficits and behavioural problems: the first disease symptom was a strong feeling of jealousy towards his wife.

  20. Anti-amnesic effect of extract and alkaloid fraction from aerial parts of Peganum harmala on scopolamine-induced memory deficits in mice.

    Science.gov (United States)

    Liu, Wei; Zhu, Yudan; Wang, Yongli; Qi, Shenglan; Wang, Yuwen; Ma, Chao; Li, Shuping; Jiang, Bo; Cheng, Xuemei; Wang, Zhengtao; Xuan, Zhenyu; Wang, Changhong

    2017-05-23

    Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb for treatment of forgetfulness in Uighur medicine in China. But, the active ingredients and underlying mechanisms are unclear. The present study was undertaken to investigate the improvement effects of extract and alkaloid fraction from APP on scopolamine-induced cognitive dysfunction and to elucidate their underlying mechanisms of action, and to support its folk use with scientific evidence, and lay a foundation for its further researches. The acetylcholinesterase (AChE) inhibitory activities of extract (EXT), alkaloid fraction (ALK) and flavonoid fraction (FLA) from APP were evaluated in normal male C57BL/6 mice. The anti-amnesic effects of EXT and ALK from APP were measured in scopolamine-induced memory deficits mice by the Morris water maze (MWM) tasks. The levels of biomarkers, enzyme activity and protein expression of cholinergic system were determined in brain tissues. The AChE activity was significantly decreased and the content of neurotransmitter acetylcholine (ACh) was significantly increased in normal mice cortex and hippocampus by treatment with donepezil at dosage of 8mg/kg, EXT at dosages of 183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (P0.05). In the MWM task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by treatment with EXT at dosages of 550, 1650mg/kg and ALK at dosages of 30, 90mg/kg (Pscopolamine-induced mice by treatment with EXT at dosages of 183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (Pmemory processes in mice with scopolamine-induced memory impairment. APP is an effective traditional folk medicine and the ALK fraction is proved to be the main effective components for the treatment of forgetfulness. The ALK may be valuable source for lead compounds discovery and drug development for treatment of memory impairment

  1. Improvement of memory and neurological deficit with Ocimum basilicum L. extract after ischemia reperfusion induced cerebral injury in mice.

    Science.gov (United States)

    Singh, Varinder; Krishan, Pawan; Shri, Richa

    2018-03-15

    Oxidative stress is strongly implicated in the pathogenesis of stroke. Strategies using antioxidants to improve neurological functions after stroke have, thus, gained significant attention. Ocimum basilicum L. is used traditionally to treat CNS disorders. Its antioxidant capacity is well established. Our laboratory has reported protective effects of pre-treatment with O. basilicum in experimental stroke, but its curative (post-treatment) effects in ischemic stroke have not been documented. Hence, the present study was aimed to evaluate the effect of O. basilicum leaf extract (OBLE) on functional outcomes following cerebral injury in mice. Cerebral injury was induced in the experimental animals by bilateral common carotid artery occlusion (BCCAO) followed by reperfusion. OBLE treatment (200 and 400 mg/kg; orally, once daily) was given for 7 days after BCCAO. Cognitive outcomes and sensorimotor disturbances were evaluated with Morris Water Maze, Elevated Plus Maze and neurological severity score, respectively. TTC (2,3,5-triphenyltetrazolium chloride) staining was used to measure cerebral infarct size. Thiobarbituric acid reactive substances, reduced glutathione levels and superoxide dismutase activity in mice brain homogenate were estimated to elucidate the neuroprotective mechanism of OBLE. Treatment with OBLE resulted in marked improvement in memory and motor coordination. OBLE also decreased cerebral infarct size and oxidative stress in mice. The extract was standardised with respect to total phenol content; an HPLC-PDA analysis showed the presence of eight phenolic acids in OBLE. It is concluded that treatment with OBLE improves functional outcomes after ischemic stroke and this may be developed as a neuroprotective drug.

  2. Extended remediation of sleep deprived-induced working memory deficits using fMRI-guided transcranial magnetic stimulation.

    Science.gov (United States)

    Luber, Bruce; Steffener, Jason; Tucker, Adrienne; Habeck, Christian; Peterchev, Angel V; Deng, Zhi-De; Basner, Robert C; Stern, Yaakov; Lisanby, Sarah H

    2013-06-01

    We attempted to prevent the development of working memory (WM) impairments caused by sleep deprivation using fMRI-guided repetitive transcranial magnetic stimulation (rTMS). Novel aspects of our fMRI-guided rTMS paradigm included the use of sophisticated covariance methods to identify functional networks in imaging data, and the use of fMRI-targeted rTMS concurrent with task performance to modulate plasticity effects over a longer term. Between-groups mixed model. TMS, MRI, and sleep laboratory study. 27 subjects (13 receiving Active rTMS, and 14 Sham) completed the sleep deprivation protocol, with another 21 (10 Active, 11 Sham) non-sleep deprived subjects run in a second experiment. Our previous covariance analysis had identified a network, including occipital cortex, which demonstrated individual differences in resilience to the deleterious effects of sleep deprivation on WM performance. Five Hz rTMS was applied to left lateral occipital cortex while subjects performed a WM task during 4 sessions over the course of 2 days of total sleep deprivation. At the end of the sleep deprivation period, Sham sleep deprived subjects exhibited degraded performance in the WM task. In contrast, those receiving Active rTMS did not show the slowing and lapsing typical in sleep deprivation, and instead performed similarly to non- sleep deprived subjects. Importantly, the Active sleep deprivation group showed rTMS-induced facilitation of WM performance a full 18 hours after the last rTMS session. Over the course of sleep deprivation, these results indicate that rTMS applied concurrently with WM task performance affected neural circuitry involved in WM to prevent its full impact.

  3. Synergistic Effects of Psychosocial Stress and Mild Peripheral Infection on Inducing Microglial Activation in the Hippocampal Dentate Gyrus and Long-Lasting Deficits in Hippocampus-Related Memory.

    Science.gov (United States)

    Tzeng, Wen-Yu; Su, Chien-Chou; Sun, Li-Han; Cherng, Chianfang G.; Yu, Lung

    2018-04-30

    Lipopolysaccharide (LPS) treatment and stress may cause immune activation in the brain, an event which has been thought to play a role in mediating stress-induced cognitive dysfunction. However, the enduring impact of psychosocial stress on brain immune activation or cognitive deficits has not been well investigated. Likewise, it remains unexplored whether there exist synergistic effects of psychosocial stress and a weak systemic LPS treatment on brain immune activation and/or cognitive function. In this work, a 10-day social defeat regimen was used to model psychosocial stress and the number and density of ionized calcium-binding adaptor molecule 1 (Iba1)-stained microglia was used to reveal brain immune activation in male Balb/C mice. The social defeat regimen did not cause observable microglial activation in dentate gyrus (DG) 24 h after the conclusion of the regimen. Microglial activation peaked in DG 24 h following a single 1 mg/kg intra-peritoneal LPS injection. At this time point, DG microglial activation was not evident providing 0.125 mg/kg or lower of LPS was used, this dose of LPS was, thus, regarded as the “sub-threshold” in this study. Twenty-four h after the conclusion of the defeat regimen, mice received a social interaction test to determine their defeat stress susceptibility and a “sub-threshold” LPS injection. DG microglial activation was observed in the defeat-stress susceptible, but not in the resilient, mice. Furthermore, the stress-susceptible mice showed impairment in object location and Y maze tasks 24 and 72 h after the “sub-threshold” LPS injection. These results suggest that psychosocial stress, when combined with a negligible peripheral infection, may induce long-lasting hippocampus-related memory deficits exclusively in subjects susceptible to psychosocial stresses.

  4. Aging-associated excess formaldehyde leads to spatial memory deficits

    Science.gov (United States)

    Tong, Zhiqian; Han, Chanshuai; Luo, Wenhong; Li, Hui; Luo, Hongjun; Qiang, Min; Su, Tao; Wu, Beibei; Liu, Ying; Yang, Xu; Wan, You; Cui, Dehua; He, Rongqiao

    2013-01-01

    Recent studies show that formaldehyde participates in DNA demethylation/methylation cycle. Emerging evidence identifies that neuronal activity induces global DNA demethylation and re-methylation; and DNA methylation is a critical step for memory formation. These data suggest that endogenous formaldehyde may intrinsically link learning-responsive DNA methylation status and memory formation. Here, we report that during spatial memory formation process, spatial training induces an initial global DNA demethylation and subsequent re-methylation associated with hippocampal formaldehyde elevation then decline to baseline level in Sprague Dawley rats. Scavenging this elevated formaldehyde by formaldehyde-degrading enzyme (FDH), or enhancing DNA demethylation by a DNA demethylating agent, both led to spatial memory deficits by blocking DNA re-methylation in rats. Furthermore, we found that the normal adult rats intrahippocampally injected with excess formaldehyde can imitate the aged-related spatial memory deficits and global DNA methylation decline. These findings indicate that aging-associated excess formaldheyde contributes to cognitive decline during aging. PMID:23657727

  5. Arctigenin Attenuates Learning and Memory Deficits through PI3k/Akt/GSK-3β Pathway Reducing Tau Hyperphosphorylation in Aβ-Induced AD Mice.

    Science.gov (United States)

    Qi, Yue; Dou, De-Qiang; Jiang, Hong; Zhang, Bing-Bing; Qin, Wen-Yan; Kang, Kai; Zhang, Na; Jia, Dong

    2017-01-01

    Arctigenin is a phenylpropanoid dibenzylbutyrolactone lignan compound possessing antitumor, anti-inflammatory, anti-influenza, antioxidant, antibacterial, and hypoglycaemic activities. Our previous study demonstrated that arctigenin exerts neuroprotective effects both in vitro and in vivo in a Parkinson's disease model. However, the exact mechanism through which arctigenin improves amyloid beta-induced memory impairment by inhibiting the production of the hyperphosphorylated tau protein is unknown. Amyloid β 1-42 was slowly administered via the intracerebroventricular route in a volume of 3 µL (≈ 410 pmmol/mouse) to mice. The mice were administered arctigenin (10, 40, or 150 mg/kg) or vehicle starting from the second day after amyloid β 1-42 injection to the end of the experiment. Behavioural tests were performed from days 9 to 15. On day 16 after the intracerebroventricular administration of amyloid β 1-42 , the mice were sacrificed for biochemical analysis. Arctigenin (10-150 mg/kg) significantly attenuated the impairment of spontaneous alternation behaviours in the Y-maze task, decreased the escape latency in the Morris water maze test, and increased the swimming times and swimming distances to the platform located in the probe test. Arctigenin attenuated the level of phosphorylated tau at the Thr-181, Thr-231, and Ser-404 sites in the hippocampus, and increased the phosphorylation levels of phosphatidylinositol-3-kinase, threonine/serine protein kinase B, and glycogen synthase kinase-3 β . Arctigenin effectively provides protection against learning and memory deficits and in inhibits hyperphosphorylated tau protein expression in the hippocampus. The possible mechanism may occur via the phosphatidylinositol-3-kinase/protein kinase B-dependent glycogen synthase kinase-3 β signalling pathway. Georg Thieme Verlag KG Stuttgart · New York.

  6. Denial of memory deficit in Alzheimer's disease.

    Science.gov (United States)

    Sevush, S; Leve, N

    1993-05-01

    Patients with probable Alzheimer's disease often deny or underestimate the severity of their memory impairment. The authors examined the relationships between denial and severity of cognitive impairment and between denial and the presence of depressed mood and sad affect in 128 patients with probable Alzheimer's disease. Denial of memory deficit was evaluated by structured interview. Cognition was evaluated with a quantitative examination that assessed performance on 16 subtests. Depression was rated by using a scale that included patients' self-ratings as well as caregivers' and examiners' assessments of the patient's mood and affect. Pearson correlation coefficients were used to quantify the relationship between denial and demographic, cognitive, and depression variables. Stepwise multiple regression analysis was used to further examine the relationship between denial and individual cognitive subset scores. Denial did not correlate with age at onset of Alzheimer's disease, duration of illness, or educational background. It did correlate with gender: women exhibited greater denial than men. A significant correlation was found between denial and overall severity of cognitive deficit and particularly with impairment in object naming. A negative correlation was found between denial and depression. The association between denial and cognitive impairment may suggest that denial of probable Alzheimer's disease results from disruption of cognitive abilities needed for awareness of illness. The negative association between denial and depression may suggest that depression in Alzheimer's disease is in part reactive in nature.

  7. Effects of ginseol k-g3, an Rg3-enriched fraction, on scopolamine-induced memory impairment and learning deficit in mice

    Directory of Open Access Journals (Sweden)

    Ike dela Peña

    2014-01-01

    Conclusion: The effects of ginseol k-g3 in ameliorating scopolamine-induced memory impairment in the passive avoidance and Morris water maze tests indicate its specific influence on reference or long-term memory. The mechanism underlying the reversal of scopolamine-induced amnesia by ginseol k-g3 is not yet known, but is not related to anticholinesterase-like activity.

  8. Inhibiting corticosterone synthesis during fear memory formation exacerbates cued fear extinction memory deficits within the single prolonged stress model.

    Science.gov (United States)

    Keller, Samantha M; Schreiber, William B; Stanfield, Briana R; Knox, Dayan

    2015-01-01

    Using the single prolonged stress (SPS) animal model of post-traumatic stress disorder (PTSD), previous studies suggest that enhanced glucocorticoid receptor (GR) expression leads to cued fear extinction retention deficits. However, it is unknown how the endogenous ligand of GRs, corticosterone (CORT), may contribute to extinction retention deficits in the SPS model. Given that CORT synthesis during fear learning is critical for fear memory consolidation and SPS enhances GR expression, CORT synthesis during fear memory formation could strengthen fear memory in SPS rats by enhancing GR activation during fear learning. In turn, this could lead to cued fear extinction retention deficits. We tested the hypothesis that CORT synthesis during fear learning leads to cued fear extinction retention deficits in SPS rats by administering the CORT synthesis inhibitor metyrapone to SPS and control rats prior to fear conditioning, and observed the effect this had on extinction memory. Inhibiting CORT synthesis during fear memory formation in control rats tended to decrease cued freezing, though this effect never reached statistical significance. Contrary to our hypothesis, inhibiting CORT synthesis during fear memory formation disrupted extinction retention in SPS rats. This finding suggests that even though SPS exposure leads to cued fear extinction memory deficits, CORT synthesis during fear memory formation enhances extinction retention in SPS rats. This suggests that stress-induced CORT synthesis in previously stressed rats can be beneficial. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Reversal of memory deficits by Coriandrum sativum leaves in mice.

    Science.gov (United States)

    Mani, Vasudevan; Parle, Milind; Ramasamy, Kalavathy; Abdul Majeed, Abu Bakar

    2011-01-15

    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. CSL (5, 10 and 15% w/w of diet) produced a dose-dependent improvement in memory scores of young as well as aged mice. CSL also reversed successfully the memory deficits induced by scopolamine (0.4 mg kg(-1), i.p.) and diazepam (1 mg kg(-1), i.p.). Interestingly, brain cholinesterase activity and serum total cholesterol levels were considerably reduced by CSL administration in daily diets concomitantly for 45 days. CSL may be a useful remedy in the management of Alzheimer's disease on account of its multifarious effects such as, memory-improving property, cholesterol-lowering property and anticholinesterase activity. Copyright © 2010 Society of Chemical Industry.

  10. Intermittent hypoxia after transient focal ischemia induces hippocampal neurogenesis and c-Fos expression and reverses spatial memory deficits in rats.

    Directory of Open Access Journals (Sweden)

    Yi-Wei Tsai

    Full Text Available Memory impairment is a frequent complication of brain ischemia. Neurogenesis is implicated in learning and memory and is regulated by the transcription factor c-Fos. Preconditioning intermittent hypoxia (IH attenuates ischemia-related memory impairments, but it is not known whether post-ischemia IH intervention has a similar effect. We investigated the effects of post-ischemia IH on hippocampal neurogenesis and c-Fos expression as well as spatial learning and memory in rats.Focal cerebral ischemia was induced in some rats by middle cerebral artery occlusion (MCAO, while other rats received sham MCAO surgery. Beginning a week later, half of the rats of each group received IH interventions (12% oxygen concentration, 4 hrs/d, for 7 d and half received sham IH sessions. An additional group of rats received MCAO, IH, and injections of the neurogenesis-impairing agent 3'-AZT. Spatial learning and memory was measured in the Morris water maze, and hippocampal neurogenesis and c-Fos expression were examined. Hypoxia-inducible factor 1α (HIF-1α and phosphorylated mitogen-activated protein kinase (pMAPK were considered as possible mediators of IH-induced changes in neurogenesis and c-Fos expression. IH intervention following MCAO resulted in recovered spatial memory, increased hippocampal neurogenesis, and increased expression of c-Fos in newborn hippocampal cells. These effects were blocked by 3'-AZT. IH intervention following MCAO also was associated with increased hippocampal pMAPK and HIF-1α expression.IH intervention following MCAO rescued ischemia-induced spatial learning and memory impairments, likely by inducing hippocampal neurogenesis and c-Fos expression through mediators including pMAPK and HIF-1α.

  11. Intermittent hypoxia after transient focal ischemia induces hippocampal neurogenesis and c-Fos expression and reverses spatial memory deficits in rats.

    Science.gov (United States)

    Tsai, Yi-Wei; Yang, Yea-Ru; Wang, Paulus S; Wang, Ray-Yau

    2011-01-01

    Memory impairment is a frequent complication of brain ischemia. Neurogenesis is implicated in learning and memory and is regulated by the transcription factor c-Fos. Preconditioning intermittent hypoxia (IH) attenuates ischemia-related memory impairments, but it is not known whether post-ischemia IH intervention has a similar effect. We investigated the effects of post-ischemia IH on hippocampal neurogenesis and c-Fos expression as well as spatial learning and memory in rats. Focal cerebral ischemia was induced in some rats by middle cerebral artery occlusion (MCAO), while other rats received sham MCAO surgery. Beginning a week later, half of the rats of each group received IH interventions (12% oxygen concentration, 4 hrs/d, for 7 d) and half received sham IH sessions. An additional group of rats received MCAO, IH, and injections of the neurogenesis-impairing agent 3'-AZT. Spatial learning and memory was measured in the Morris water maze, and hippocampal neurogenesis and c-Fos expression were examined. Hypoxia-inducible factor 1α (HIF-1α) and phosphorylated mitogen-activated protein kinase (pMAPK) were considered as possible mediators of IH-induced changes in neurogenesis and c-Fos expression. IH intervention following MCAO resulted in recovered spatial memory, increased hippocampal neurogenesis, and increased expression of c-Fos in newborn hippocampal cells. These effects were blocked by 3'-AZT. IH intervention following MCAO also was associated with increased hippocampal pMAPK and HIF-1α expression. IH intervention following MCAO rescued ischemia-induced spatial learning and memory impairments, likely by inducing hippocampal neurogenesis and c-Fos expression through mediators including pMAPK and HIF-1α.

  12. TrkB overexpression in mice buffers against memory deficits and depression-like behavior but not all anxiety- and stress-related symptoms induced by developmental exposure to methylmercury

    Directory of Open Access Journals (Sweden)

    Nina N Karpova

    2014-09-01

    Full Text Available Developmental exposure to low dose of methylmercury (MeHg has a long-lasting effect on memory and attention deficits in humans, as well as cognitive performance, depression-like behavior and the hippocampal levels of the brain-derived neurotrophic factor (Bdnfin mice. The Bdnf receptor TrkB is a key player of Bdnf signaling. Using transgenic animals, here we analyzed the effect of the full-length TrkB overexpression (TK+ on behavior impairments induced by perinatal MeHg. TK overexpression in the MeHg-exposed mice enhanced generalized anxiety and cue memory in the fear conditioning test. Early exposure to MeHg induced deficits in reversal spatial memory in the Morris water maze test and depression-like behavior in the forced swim test in only wild-type mice but did not affect these parameters in TK+ mice. These changes were associated with TK+ effect on the increase in Bdnf 2, 3, 4 and 6 transcription in the hippocampus as well as with interaction of TK+ and MeHg factors for Bdnf 1, 9a and truncated TrkB.T1 transcripts in the prefrontal cortex. However, the MeHg-induced anxiety-like behavior in the elevated plus maze and open field tests was ameliorated by TK+ background only in the open field test. Moreover, TK overexpression in the MeHg mice did not prevent significant stress-induced weight loss during the period of adaptation to individual housing in metabolic cages. These TK genotype-independent changes were primarily accompanied by the MeHg-induced hippocampal deficits in the activity-dependent Bdnf 1, 4 and 9a variants, TrkB.T1, and transcripts for important antioxidant enzymes glyoxalases Glo1 and Glo2 and glutathione reductase Gsr. Our data suggest a role of full-length TrkB in buffering against memory deficits and depression-like behavior in the MeHg mice but propose the involvement of additional pathways, such as the antioxidant system or TrkB.T1 signaling, in stress- or anxiety-related responses induced by developmental MeHg exposure.

  13. Sleep Restores Daytime Deficits in Procedural Memory in Children with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Prehn-Kristensen, Alexander; Molzow, Ina; Munz, Manuel; Wilhelm, Ines; Muller, Kathrin; Freytag, Damaris; Wiesner, Christian D.; Baving, Lioba

    2011-01-01

    Sleep supports the consolidation of declarative and procedural memory. While prefrontal cortex (PFC) activity supports the consolidation of declarative memory during sleep, opposite effects of PFC activity are reported with respect to the consolidation of procedural memory during sleep. Patients with attention-deficit/hyperactivity disorder (ADHD)…

  14. Verbal declarative memory impairments in specific language impairment are related to working memory deficits.

    Science.gov (United States)

    Lum, Jarrad A G; Ullman, Michael T; Conti-Ramsden, Gina

    2015-03-01

    This study examined verbal declarative memory functioning in SLI and its relationship to working memory. Encoding, recall, and recognition of verbal information was examined in children with SLI who had below average working memory (SLILow WM), children with SLI who had average working memory (SLIAvg. WM) and, a group of non-language impaired children with average working memory (TDAvg. WM). The SLILow WM group was significantly worse than both the SLIAvg. WM and TDAvg. WM groups at encoding verbal information and at retrieving verbal information following a delay. In contrast, the SLIAvg. WM group showed no verbal declarative memory deficits. The study demonstrates that verbal declarative memory deficits in SLI only occur when verbal working memory is impaired. Thus SLI declarative memory is largely intact and deficits are likely to be related to working memory impairments. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  15. Complex Prospective Memory in Adults with Attention Deficit Hyperactivity Disorder

    NARCIS (Netherlands)

    Fuermaier, Anselm B. M.; Tucha, Lara; Koerts, Janneke; Aschenbrenner, Steffen; Westermann, Celina; Weisbrod, Matthias; Lange, Klaus W.; Tucha, Oliver

    2013-01-01

    Objectives: Attention deficit hyperactivity disorder (ADHD) in adults has been associated with disturbances of attention and executive functions. Furthermore, impairments of verbal and figural retrospective memory were reported. However, little is known about the effects of ADHD on prospective

  16. Encoding, Memory, and Transcoding Deficits in Childhood Apraxia of Speech

    Science.gov (United States)

    Shriberg, Lawrence D.; Lohmeier, Heather L.; Strand, Edythe A.; Jakielski, Kathy J.

    2012-01-01

    A central question in Childhood Apraxia of Speech (CAS) is whether the core phenotype is limited to transcoding (planning/programming) deficits or if speakers with CAS also have deficits in auditory-perceptual "encoding" (representational) and/or "memory" (storage and retrieval of representations) processes. We addressed this and other questions…

  17. Effects of ginseol k-g3, an Rg3-enriched fraction, on scopolamine-induced memory impairment and learning deficit in mice.

    Science.gov (United States)

    Peña, Ike Dela; Yoon, Seo Young; Kim, Hee Jin; Park, Sejin; Hong, Eun Young; Ryu, Jong Hoon; Park, Il Ho; Cheong, Jae Hoon

    2014-01-01

    Although ginsenosides such as Rg1, Rb1 and Rg3 have shown promise as potential nutraceuticals for cognitive impairment, their use has been limited due to high production cost and low potency. In particular, the process of extracting pure Rg3 from ginseng is laborious and expensive. We described the methods in preparing ginseol k-g3, an Rg3-enriched fraction, and evaluated its effects on scopolamine-induced memory impairment in mice. Ginseol k-g3 (25-200 mg/kg) significantly reversed scopolamine-induced cognitive impairment in the passive avoidance, but not in Y-maze testing. Ginseol k-g3 (50 and 200 mg/kg) improved escape latency in training trials and increased swimming times within the target zone of the Morris water maze. The effect of ginseol k-g3 on the water maze task was more potent than that of Rg3 or Red ginseng. Acute or subchronic (6 d) treatment of ginseol k-g3 did not alter normal locomotor activity of mice in an open field. Ginseol k-g3 did not inhibit acetylcholinesterase activity, unlike donezepil, an acetylcholinesterase inhibitor. Rg3 enrichment through the ginseol k-g3 fraction enhanced the efficacy of Rg3 in scopolamine-induced memory impairment in mice as demonstrated in the Morris water maze task. The effects of ginseol k-g3 in ameliorating scopolamine-induced memory impairment in the passive avoidance and Morris water maze tests indicate its specific influence on reference or long-term memory. The mechanism underlying the reversal of scopolamine-induced amnesia by ginseol k-g3 is not yet known, but is not related to anticholinesterase-like activity.

  18. Nicotine Administration Attenuates Methamphetamine-Induced Novel Object Recognition Deficits.

    Science.gov (United States)

    Vieira-Brock, Paula L; McFadden, Lisa M; Nielsen, Shannon M; Smith, Misty D; Hanson, Glen R; Fleckenstein, Annette E

    2015-07-11

    Previous studies have demonstrated that methamphetamine abuse leads to memory deficits and these are associated with relapse. Furthermore, extensive evidence indicates that nicotine prevents and/or improves memory deficits in different models of cognitive dysfunction and these nicotinic effects might be mediated by hippocampal or cortical nicotinic acetylcholine receptors. The present study investigated whether nicotine attenuates methamphetamine-induced novel object recognition deficits in rats and explored potential underlying mechanisms. Adolescent or adult male Sprague-Dawley rats received either nicotine water (10-75 μg/mL) or tap water for several weeks. Methamphetamine (4 × 7.5mg/kg/injection) or saline was administered either before or after chronic nicotine exposure. Novel object recognition was evaluated 6 days after methamphetamine or saline. Serotonin transporter function and density and α4β2 nicotinic acetylcholine receptor density were assessed on the following day. Chronic nicotine intake via drinking water beginning during either adolescence or adulthood attenuated the novel object recognition deficits caused by a high-dose methamphetamine administration. Similarly, nicotine attenuated methamphetamine-induced deficits in novel object recognition when administered after methamphetamine treatment. However, nicotine did not attenuate the serotonergic deficits caused by methamphetamine in adults. Conversely, nicotine attenuated methamphetamine-induced deficits in α4β2 nicotinic acetylcholine receptor density in the hippocampal CA1 region. Furthermore, nicotine increased α4β2 nicotinic acetylcholine receptor density in the hippocampal CA3, dentate gyrus and perirhinal cortex in both saline- and methamphetamine-treated rats. Overall, these findings suggest that nicotine-induced increases in α4β2 nicotinic acetylcholine receptors in the hippocampus and perirhinal cortex might be one mechanism by which novel object recognition deficits are

  19. A heuristic model for working memory deficit in schizophrenia.

    Science.gov (United States)

    Qi, Zhen; Yu, Gina P; Tretter, Felix; Pogarell, Oliver; Grace, Anthony A; Voit, Eberhard O

    2016-11-01

    The life of schizophrenia patients is severely affected by deficits in working memory. In various brain regions, the reciprocal interactions between excitatory glutamatergic neurons and inhibitory GABAergic neurons are crucial. Other neurotransmitters, in particular dopamine, serotonin, acetylcholine, and norepinephrine, modulate the local balance between glutamate and GABA and therefore regulate the function of brain regions. Persistent alterations in the balances between the neurotransmitters can result in working memory deficits. Here we present a heuristic computational model that accounts for interactions among neurotransmitters across various brain regions. The model is based on the concept of a neurochemical interaction matrix at the biochemical level and combines this matrix with a mobile model representing physiological dynamic balances among neurotransmitter systems associated with working memory. The comparison of clinical and simulation results demonstrates that the model output is qualitatively very consistent with the available data. In addition, the model captured how perturbations migrated through different neurotransmitters and brain regions. Results showed that chronic administration of ketamine can cause a variety of imbalances, and application of an antagonist of the D2 receptor in PFC can also induce imbalances but in a very different manner. The heuristic computational model permits a variety of assessments of genetic, biochemical, and pharmacological perturbations and serves as an intuitive tool for explaining clinical and biological observations. The heuristic model is more intuitive than biophysically detailed models. It can serve as an important tool for interdisciplinary communication and even for psychiatric education of patients and relatives. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Arctigenin isolated from the seeds of Arctium lappa ameliorates memory deficits in mice.

    Science.gov (United States)

    Lee, In-Ah; Joh, Eun-Ha; Kim, Dong-Hyun

    2011-09-01

    The seeds of Arctium lappa L. (AL, family Asteraceae), the main constituents of which are arctiin and arctigenin, have been used as an herbal medicine or functional food to treat inflammatory diseases. These main constituents were shown to inhibit acetylcholinesterase (AChE) activity. Arctigenin more potently inhibited AChE activity than arctiin. Arctigenin at doses of 30 and 60 mg/kg (p. o.) potently reversed scopolamine-induced memory deficits by 62 % and 73 %, respectively, in a passive avoidance test. This finding is comparable with that of tacrine (10 mg/kg p. o.). Arctigenin also significantly reversed scopolamine-induced memory deficits in the Y-maze and Morris water maze tests. On the basis of these findings, arctigenin may ameliorate memory deficits by inhibiting AChE. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Neuropeptide VGF C-Terminal Peptide TLQP-62 Alleviates Lipopolysaccharide-Induced Memory Deficits and Anxiety-like and Depression-like Behaviors in Mice: The Role of BDNF/TrkB Signaling.

    Science.gov (United States)

    Li, Chenli; Li, Mengmeng; Yu, Hanjie; Shen, Xinbei; Wang, Jinting; Sun, Xin; Wang, Qinwen; Wang, Chuang

    2017-09-20

    Peripheral inflammatory responses affect central nervous system (CNS) function, manifesting in symptoms of memory deficits, depression, and anxiety. Previous studies have revealed that neuropeptide VGF (nonacronymic) C-terminal peptide TLQP-62 rapidly reinforces brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling, regulating memory consolidation and antidepressant-like action. However, whether it is beneficial for lipopolysaccharide (LPS)-induced neuropsychiatric dysfunction in mice is unknown. Herein, we explored the involvement of BDNF/TrkB signaling and biochemical alterations in inflammatory or oxidative stress markers in the alleviating effects of TLQP-62 on LPS-induced neuropsychiatric dysfunction. The mice were treated with TLQP-62 (2 μg/side) via intracerebroventricular (i.c.v.) injection 1 h before LPS (0.5 mg/kg, i.p.) administration. Our results showed that a single treatment with LPS (0.5 mg/kg, i.p) is sufficient to produce recognition memory deficits (in the novel object recognition test), depression-like behavior (in the forced swim test and sucrose preference test), and anxiety-like behavior (in the elevated zero maze). However, pretreatment with TLQP-62 prevented LPS-induced behavioral dysfunction, neuroinflammatory, and oxidative responses. In addition, our results further demonstrated that a reduction in BDNF expression mediated by BDNF-shRNA lentivirus significantly blocked the effects of TLQP-62, suggesting the critical role of BDNF/TrkB signaling in the neuroprotective effects of TLQP-62 in the mice. In conclusion, TLQP-62 could be a therapeutic approach for neuropsychiatric disorders, which are closely associated with neuroinflammation and oxidative stress.

  2. The Impact of Visual Memory Deficits on Academic Achievement in Children and Adolescents

    Science.gov (United States)

    Larsen, Jessica Maria

    2011-01-01

    Memory assessment can often alert practitioners and educators to learning problems children may be experiencing. Results of a memory assessment may indicate that a child has a specific memory deficit in verbal memory, visual memory, or both. Deficits in visual or verbal modes of memory could potentially have adverse effects on academic…

  3. Effects of ginseol k-g3, an Rg3-enriched fraction, on scopolamine-induced memory impairment and learning deficit in mice

    OpenAIRE

    Peña, Ike dela; Yoon, Seo Young; Kim, Hee Jin; Park, Sejin; Hong, Eun Young; Ryu, Jong Hoon; Park, Il Ho; Cheong, Jae Hoon

    2013-01-01

    Background: Although ginsenosides such as Rg1, Rb1 and Rg3 have shown promise as potential nutraceuticals for cognitive impairment, their use has been limited due to high production cost and low potency. In particular, the process of extracting pure Rg3 from ginseng is laborious and expensive. Methods: We described the methods in preparing ginseol k-g3, an Rg3-enriched fraction, and evaluated its effects on scopolamine-induced memory impairment in mice. Results: Ginseol k-g3 (25–200 mg/...

  4. Chronic Hippocampal Expression of Notch Intracellular Domain Induces Vascular Thickening, Reduces Glucose Availability, and Exacerbates Spatial Memory Deficits in a Rat Model of Early Alzheimer.

    Science.gov (United States)

    Galeano, Pablo; Leal, María C; Ferrari, Carina C; Dalmasso, María C; Martino Adami, Pamela V; Farías, María I; Casabona, Juan C; Puntel, Mariana; Do Carmo, Sonia; Smal, Clara; Arán, Martín; Castaño, Eduardo M; Pitossi, Fernando J; Cuello, A Claudio; Morelli, Laura

    2018-03-26

    The specific roles of Notch in progressive adulthood neurodegenerative disorders have begun to be unraveled in recent years. A number of independent studies have shown significant increases of Notch expression in brains from patients at later stages of sporadic Alzheimer's disease (AD). However, the impact of Notch canonical signaling activation in the pathophysiology of AD is still elusive. To further investigate this issue, 2-month-old wild-type (WT) and hemizygous McGill-R-Thy1-APP rats (Tg(+/-)) were injected in CA1 with lentiviral particles (LVP) expressing the transcriptionally active fragment of Notch, known as Notch Intracellular Domain (NICD), (LVP-NICD), or control lentivirus particles (LVP-C). The Tg(+/-) rat model captures presymptomatic aspects of the AD pathology, including intraneuronal amyloid beta (Aβ) accumulation and early cognitive deficits. Seven months after LVP administration, Morris water maze test was performed, and brains isolated for biochemical and histological analysis. Our results showed a learning impairment and a worsening of spatial memory in LVP-NICD- as compared to LVP-C-injected Tg(+/-) rats. In addition, immuno histochemistry, ELISA multiplex, Western blot, RT-qPCR, and 1 H-NMR spectrometry of cerebrospinal fluid (CSF) indicated that chronic expression of NICD promoted hippocampal vessel thickening with accumulation of Aβ in brain microvasculature, alteration of blood-brain barrier (BBB) permeability, and a decrease of CSF glucose levels. These findings suggest that, in the presence of early Aβ pathology, expression of NICD may contribute to the development of microvascular abnormalities, altering glucose transport at the BBB with impact on early decline of spatial learning and memory.

  5. Effects of acute administration of donepezil or memantine on sleep-deprivation-induced spatial memory deficit in young and aged non-human primate grey mouse lemurs (Microcebus murinus.

    Directory of Open Access Journals (Sweden)

    Anisur Rahman

    Full Text Available The development of novel therapeutics to prevent cognitive decline of Alzheimer's disease (AD is facing paramount difficulties since the translational efficacy of rodent models did not resulted in better clinical results. Currently approved treatments, including the acetylcholinesterase inhibitor donepezil (DON and the N-methyl-D-aspartate antagonist memantine (MEM provide marginal therapeutic benefits to AD patients. There is an urgent need to develop a predictive animal model that is phylogenetically proximal to humans to achieve better translation. The non-human primate grey mouse lemur (Microcebus murinus is increasingly used in aging research, but there is no published results related to the impact of known pharmacological treatments on age-related cognitive impairment observed in this primate. In the present study we investigated the effects of DON and MEM on sleep-deprivation (SD-induced memory impairment in young and aged male mouse lemurs. In particular, spatial memory impairment was evaluated using a circular platform task after 8 h of total SD. Acute single doses of DON or MEM (0.1 and 1mg/kg or vehicle were administered intraperitoneally 3 h before the cognitive task during the SD procedure. Results indicated that both doses of DON were able to prevent the SD-induced deficits in retrieval of spatial memory as compared to vehicle-treated animals, both in young and aged animals Likewise, MEM show a similar profile at 1 mg/kg but not at 0.1mg/kg. Taken together, these results indicate that two widely used drugs for mitigating cognitive deficits in AD were partially effective in sleep deprived mouse lemurs, which further support the translational potential of this animal model. Our findings demonstrate the utility of this primate model for further testing cognitive enhancing drugs in development for AD or other neuropsychiatric conditions.

  6. Effects of acute administration of donepezil or memantine on sleep-deprivation-induced spatial memory deficit in young and aged non-human primate grey mouse lemurs (Microcebus murinus).

    Science.gov (United States)

    Rahman, Anisur; Lamberty, Yves; Schenker, Esther; Cella, Massimo; Languille, Solène; Bordet, Régis; Richardson, Jill; Pifferi, Fabien; Aujard, Fabienne

    2017-01-01

    The development of novel therapeutics to prevent cognitive decline of Alzheimer's disease (AD) is facing paramount difficulties since the translational efficacy of rodent models did not resulted in better clinical results. Currently approved treatments, including the acetylcholinesterase inhibitor donepezil (DON) and the N-methyl-D-aspartate antagonist memantine (MEM) provide marginal therapeutic benefits to AD patients. There is an urgent need to develop a predictive animal model that is phylogenetically proximal to humans to achieve better translation. The non-human primate grey mouse lemur (Microcebus murinus) is increasingly used in aging research, but there is no published results related to the impact of known pharmacological treatments on age-related cognitive impairment observed in this primate. In the present study we investigated the effects of DON and MEM on sleep-deprivation (SD)-induced memory impairment in young and aged male mouse lemurs. In particular, spatial memory impairment was evaluated using a circular platform task after 8 h of total SD. Acute single doses of DON or MEM (0.1 and 1mg/kg) or vehicle were administered intraperitoneally 3 h before the cognitive task during the SD procedure. Results indicated that both doses of DON were able to prevent the SD-induced deficits in retrieval of spatial memory as compared to vehicle-treated animals, both in young and aged animals Likewise, MEM show a similar profile at 1 mg/kg but not at 0.1mg/kg. Taken together, these results indicate that two widely used drugs for mitigating cognitive deficits in AD were partially effective in sleep deprived mouse lemurs, which further support the translational potential of this animal model. Our findings demonstrate the utility of this primate model for further testing cognitive enhancing drugs in development for AD or other neuropsychiatric conditions.

  7. Memory deficits associated with sublethal cyanide poisoning relative to cyanate toxicity in rodents.

    Science.gov (United States)

    Kimani, S; Sinei, K; Bukachi, F; Tshala-Katumbay, D; Maitai, C

    2014-03-01

    Food (cassava) linamarin is metabolized into neurotoxicants cyanide and cyanate, metabolites of which we sought to elucidate the differential toxicity effects on memory. Young 6-8 weeks old male rats were treated intraperitoneally with either 2.5 mg/kg body weight (bw) cyanide (NaCN), or 50 mg/kg bw cyanate (NaOCN), or 1 μl/g bw saline, daily for 6 weeks. Short-term and long-term memories were assessed using a radial arm maze (RAM) testing paradigm. Toxic exposures had an influence on short-term working memory with fewer correct arm entries (F(2, 19) = 4.57 p memory errors (WME) (F(2, 19) = 5.09, p RAM navigation time (F(2, 19) = 3.91, p memory was significantly impaired by cyanide with fewer correct arm entries (F(2, 19) = 7.45, p memory errors (F(2, 19) = 9.35 p memory was not affected by either cyanide or cyanate. Our study findings provide an experimental evidence for the biological plausibility that cassava cyanogens may induce cognition deficits. Differential patterns of memory deficits may reflect the differences in toxicity mechanisms of NaOCN relative to NaCN. Cognition deficits associated with cassava cyanogenesis may reflect a dual toxicity effect of cyanide and cyanate.

  8. Evaluation of Bacopa monniera for its synergistic activity with rivastigmine in reversing aluminum-induced memory loss and learning deficit in rats.

    Science.gov (United States)

    Thippeswamy, Agadi Hiremath; Rafiq, Mohamed; Viswantha, Gollapalle Lakshminarayana Shastry; Kavya, Kethaganahalli J; Anturlikar, Suryakanth D; Patki, Pralhad S

    2013-08-01

    The objective of this study was to evaluate the synergistic activity of Bacopa monniera with Rivastigmine against aluminum-chloride (AlCl3)-induced cognitive impairment in rats. Adult male Wistar rats were divided into ten groups (n = 10) and subjected to their assigned treatments for 42 days. On the 20(th) day of the respective drug treatments, all the animals were trained in the Morris water maze (retention latency) and the elevated plus maze (transfer latency). After the initial training, the retention latency (RL) and the transfer latency (TL) were evaluated on the 21(st) and the 42(nd) days of the study. Chronic administration of AlCl3 caused significant memory impairment associated with increased RL in the Morris water maze task and increased TL in the elevated plus maze test. Interestingly, animals treated with oral administration of B. monniera (100 and 200 mg/kg), Rivastigmine (5 mg/kg) or a combination of B. monniera (100 mg/kg) with Rivastigmine (5 mg/kg) showed significant protection against AlCl3-induced memory impairment compared to animal treated with AlCl3per se. Additionally, the neuroprotective effect of B. monniera (100 and 200 mg/kg) was significantly improved when supplemented with Rivastigmine (5 mg/kg). These findings suggest that treatment with a combination of B. monniera with Rivastigmine may be highly beneficial compared to their per-se treatment. Copyright © 2013. Published by Elsevier B.V.

  9. Can DRYAD explain age-related associative memory deficits?

    Science.gov (United States)

    Smyth, Andrea C; Naveh-Benjamin, Moshe

    2016-02-01

    A recent interesting theoretical account of aging and memory judgments, the DRYAD (density of representations yields age-related deficits; Benjamin, 2010; Benjamin, Diaz, Matzen, & Johnson, 2012), attributes the extensive findings of disproportional age-related deficits in memory for source, context, and associations, to a global decline in memory fidelity. It is suggested that this global deficit, possibly due to a decline in attentional processes, is moderated by weak representation of contextual information to result in disproportional age-related declines. In the current article, we evaluate the DRYAD model, comparing it to specific age-related deficits theories, in particular, the ADH (associative deficit hypothesis, Naveh-Benjamin, 2000). We question some of the main assumptions/hypotheses of DRYAD in light of data reported in the literature, and we directly assess the role of attention in age-related deficits by manipulations of divided attention and of the instructions regarding what to pay attention to in 2 experiments (one from the literature and a new one). The results of these experiments fit the predictions of the ADH and do not support the main assumption/hypotheses of DRYAD. (c) 2016 APA, all rights reserved).

  10. Working Memory - Theory, Deficits, Diagnosis, and Vision Therapy

    OpenAIRE

    Sidney Groffman, OD, MA

    2014-01-01

    Working memory (WM) is one of the most significant psychological ideas developed in the last forty years. WM is the cognitive function responsible for storing information, manipulating it, and using it in thinking. WM is a multidimensional system comprising three separable yet interactive domains. They are an executive domain and verbal and visual domains. Working memory affects many perceptuo-cognitive activities, and WM deficits can create a variety of problems, many of which fa...

  11. Effects of medicinal plants on Alzheimer's disease and memory deficits

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    Muhammad Akram

    2017-01-01

    Full Text Available Alzheimer's disease is an age-related neurodegenerative disorder characterized by memory deficits. Various studies have been carried out to find therapeutic approaches for Alzheimer's disease. However, the proper treatment option is still not available. There is no cure for Alzheimer's disease, but symptomatic treatment may improve the memory and other dementia related problems. Traditional medicine is practiced worldwide as memory enhancer since ancient times. Natural therapy including herbs and medicinal plants has been used in the treatment of memory deficits such as dementia, amnesia, as well as Alzheimer's disease since a long time. Medicinal plants have been used in different systems of medicine, particularly Unani system of medicines and exhibited their powerful roles in the management and cure of memory disorders. Most of herbs and plants have been chemically evaluated and their efficacy has also been proven in clinical trials. However, the underlying mechanisms of actions are still on the way. In this paper, we have reviewed the role of different medicinal plants that play an important role in the treatment of Alzheimer's disease and memory deficits using conventional herbal therapy.

  12. Memory deficit in patients with schizophrenia and posttraumatic stress disorder: relational vs item-specific memory

    Directory of Open Access Journals (Sweden)

    Jung W

    2016-05-01

    Full Text Available Wookyoung Jung,1 Seung-Hwan Lee1,2 1Clinical Emotions and Cognition Research Laboratory, Department of Psychiatry, Inje University, Ilsan-Paik Hospital, 2Department of Psychiatry, Inje University, Ilsan-Paik Hospital, Goyang, Korea Abstract: It has been well established that patients with schizophrenia have impairments in cognitive functioning and also that patients who experienced traumatic events suffer from cognitive deficits. Of the cognitive deficits revealed in schizophrenia or posttraumatic stress disorder (PTSD patients, the current article provides a brief review of deficit in episodic memory, which is highly predictive of patients’ quality of life and global functioning. In particular, we have focused on studies that compared relational and item-specific memory performance in schizophrenia and PTSD, because measures of relational and item-specific memory are considered the most promising constructs for immediate tangible development of clinical trial paradigm. The behavioral findings of schizophrenia are based on the tasks developed by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS initiative and the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS Consortium. The findings we reviewed consistently showed that schizophrenia and PTSD are closely associated with more severe impairments in relational memory compared to item-specific memory. Candidate brain regions involved in relational memory impairment in schizophrenia and PTSD are also discussed. Keywords: schizophrenia, posttraumatic stress disorder, episodic memory deficit, relational memory, item-specific memory, prefrontal cortex, hippocampus

  13. Everyday memory deficits in ecstasy-polydrug users.

    Science.gov (United States)

    Montgomery, Catharine; Fisk, John E

    2007-09-01

    Recent research suggests that not only does the use of recreational drugs impact on working memory functioning, but more ;everyday' aspects of memory (e.g. remembering to do something in the future) are also affected. Forty-three ecstasy-polydrug users and 51 non-ecstasy users were recruited from a university population. Each participant completed the Cognitive Failures Questionnaire (CFQ) and Everyday Memory Questionnaire (EMQ). Of these, 28 ecstasy-polydrug users and 35 non-ecstasy users completed the Prospective Memory Questionnaire (PMQ). In addition, an objective measure of cognitive failures (the CFQ-for-others) was completed by friends of participants. With the exception of the CFQ-for-others, in each regression equation, cannabis emerged as the only significant predictor of everyday and prospective memory deficits. Significant correlations were found between the different indicators of everyday memory and various measures of illicit drug use. Cannabis featured prominently in this respect. The present study provides further support for cannabis related deficits in aspects of everyday memory functioning. Ecstasy may aLso be associated with cognitive slips, but not to the same extent as cannabis.

  14. The neuroscience of positive memory deficits in depression

    Science.gov (United States)

    Dillon, Daniel G.

    2015-01-01

    Adults with unipolar depression typically show poor episodic memory for positive material, but the neuroscientific mechanisms responsible for this deficit have not been characterized. I suggest a simple hypothesis: weak memory for positive material in depression reflects disrupted communication between the mesolimbic dopamine pathway and medial temporal lobe (MTL) memory systems during encoding. This proposal draws on basic research showing that dopamine release in the hippocampus is critical for the transition from early- to late-phase long-term potentiation (LTP) that marks the conversion of labile, short-term memories into stable, long-term memories. Neuroimaging and pharmacological data from healthy humans paint a similar picture: activation of the mesolimbic reward circuit enhances encoding and boosts retention. Unipolar depression is characterized by anhedonia–loss of pleasure–and reward circuit dysfunction, which is believed to reflect negative effects of stress on the mesolimbic dopamine pathway. Thus, I propose that the MTL is deprived of strengthening reward signals in depressed adults and memory for positive events suffers accordingly. Although other mechanisms are important, this hypothesis holds promise as an explanation for positive memory deficits in depression. PMID:26441703

  15. The neuroscience of positive memory deficits in depression

    Directory of Open Access Journals (Sweden)

    Daniel Gerard Dillon

    2015-09-01

    Full Text Available Adults with unipolar depression typically show poor episodic memory for positive material, but the neuroscientific mechanisms responsible for this deficit have not been characterized. I suggest a simple hypothesis: weak memory for positive material in depression reflects disrupted communication between the mesolimbic dopamine pathway and medial temporal lobe (MTL memory systems during encoding. This proposal draws on basic research showing that dopamine release in the hippocampus is critical for the transition from early- to late-phase long-term potentiation (LTP that marks the conversion of labile, short-term memories into stable, long-term memories. Neuroimaging and pharmacological data from healthy humans paint a similar picture: activation of the mesolimbic reward circuit enhances encoding and boosts retention. Unipolar depression is characterized by anhedonia--loss of pleasure--and reward circuit dysfunction, which is believed to reflect negative effects of stress on the mesolimbic dopamine pathway. Thus, I propose that the MTL is deprived of strengthening reward signals in depressed adults and memory for positive events suffers accordingly. Although other mechanisms are important, this hypothesis holds promise as an explanation for positive memory deficits in depression.

  16. Hippocampal Physiology, Structure and Function and the Neuroscience of Schizophrenia: A Unified Account of Declarative Memory Deficits, Working Memory Deficits and Schizophrenic Symptoms

    Directory of Open Access Journals (Sweden)

    Cynthia G. Wible

    2013-06-01

    Full Text Available Memory impairment is a consistent feature of the schizophrenic syndrome. Hippocampal dysfunction has also been consistently demonstrated. This review will discuss neurophysiological and neuroanatomical aspects of memory formation and how they relate to memory impairment in schizophrenia. An understanding of the cellular physiology and connectivity of the hippocampus with other regions can also aid in understanding the relationship between schizophrenic declarative or relational memory deficits, working memory deficits and the clinical symptoms of the syndrome.

  17. The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2

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    Cline Brandon H

    2012-09-01

    Full Text Available Abstract Background A number of epidemiological studies have established a link between insulin resistance and the prevalence of depression. The occurrence of depression was found to precede the onset of diabetes and was hypothesized to be associated with inherited inter-related insufficiency of the peripheral and central insulin receptors. Recently, dicholine succinate, a sensitizer of the neuronal insulin receptor, was shown to stimulate insulin-dependent H2O2 production of the mitochondrial respiratory chain leading to an enhancement of insulin receptor autophosphorylation in neurons. As such, this mechanism can be a novel target for the elevation of insulin signaling. Results Administration of DS (25 mg/kg/day, intraperitoneal in CD1 mice for 7 days prior to the onset of stress procedure, diminished manifestations of anhedonia defined in a sucrose test and behavioral despair in the forced swim test. Treatment with dicholine succinate reduced the anxiety scores of stressed mice in the dark/light box paradigm, precluded stress-induced decreases of long-term contextual memory in the step-down avoidance test and hippocampal gene expression of IGF2. Conclusions Our data suggest that dicholine succinate has an antidepressant-like effect, which might be mediated via the up-regulation of hippocampal expression of IGF2, and implicate the neuronal insulin receptor in the pathogenesis of stress-induced depressive syndrome.

  18. Lentivirus-mediated interleukin-1β (IL-1β) knock-down in the hippocampus alleviates lipopolysaccharide (LPS)-induced memory deficits and anxiety- and depression-like behaviors in mice.

    Science.gov (United States)

    Li, Mengmeng; Li, Chenli; Yu, Hanjie; Cai, Xiongxiong; Shen, Xinbei; Sun, Xin; Wang, Jinting; Zhang, Yanhua; Wang, Chuang

    2017-09-20

    Recent evidence has suggested that peripheral inflammatory responses induced by lipopolysaccharides (LPS) play an important role in neuropsychiatric dysfunction in rodents. Interleukin-1β (IL-1β), a pro-inflammatory cytokine, has been proposed to be a key mediator in a variety of behavioral dysfunction induced by LPS in mice. Thus, inhibition of IL-1β may have a therapeutic benefit in the treatment of neuropsychiatric disorders. However, the precise underlying mechanism of knock-down of IL-1β in repairing behavioral changes by LPS remains unclear. The mice were treated with either IL-1β shRNA lentivirus or non-silencing shRNA control (NS shRNA) lentivirus by microinjection into the dentate gyrus (DG) regions of the hippocampus. After 7 days of recovery, LPS (1 mg/kg, i.p.) or saline was administered. The behavioral task for memory deficits was conducted in mice by the novel object recognition test (NORT), the anxiety-like behaviors were evaluated by the elevated zero maze (EZM), and the depression-like behaviors were examined by the sucrose preference test (SPT) and the forced swimming test (FST). Furthermore, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), nuclear factor erythroid-derived 2-like 2 (Nrf2), heme oxygenase 1 (HO1), IL-1β, tumor necrosis factor (TNF-α), neuropeptide VGF (non-acronymic), and brain-derived neurotrophic factor (BDNF) were assayed. Our results demonstrated that IL-1β knock-down in the hippocampus significantly attenuated the memory deficits and anxiety- and depression-like behaviors induced by LPS in mice. In addition, IL-1β knock-down ameliorated the oxidative and neuroinflammatory responses and abolished the downregulation of VGF and BDNF induced by LPS. Collectively, our findings suggest that IL-1β is necessary for the oxidative and neuroinflammatory responses produced by LPS and offers a novel drug target in the IL-1β/oxidative/neuroinflammatory/neurotrophic pathway for treating neuropsychiatric disorders

  19. Common Cognitive Deficits in Children with Attention-Deficit/Hyperactivity Disorder and Autism: Working Memory and Visual-Motor Integration

    Science.gov (United States)

    Englund, Julia A.; Decker, Scott L.; Allen, Ryan A.; Roberts, Alycia M.

    2014-01-01

    Cognitive deficits in working memory (WM) are characteristic features of Attention-Deficit/Hyperactivity Disorder (ADHD) and autism. However, few studies have investigated cognitive deficits using a wide range of cognitive measures. We compared children with ADHD ("n" = 49) and autism ("n" = 33) with a demographically matched…

  20. Working memory deficits in adults with ADHD: is there evidence for subtype differences?

    OpenAIRE

    Schweitzer, Julie B; Hanford, Russell B; Medoff, Deborah R

    2006-01-01

    Abstract Background Working memory performance is important for maintaining functioning in cognitive, academic and social activities. Previous research suggests there are prevalent working memory deficits in children with attention deficit hyperactivity disorder (ADHD). There is now a growing body of literature characterizing working memory functioning according to ADHD subtypes in children. The expression of working memory deficits in adults with ADHD and how they vary according to subtype, ...

  1. Ameliorative effects of yokukansan on learning and memory deficits in olfactory bulbectomized mice.

    Science.gov (United States)

    Yamada, Marina; Hayashida, Miki; Zhao, Qi; Shibahara, Naotoshi; Tanaka, Ken; Miyata, Takeshi; Matsumoto, Kinzo

    2011-06-01

    Yokukansan (YKS) is a Japanese traditional herbal medicine and has been used for the treatment of the behavioral and psychological symptoms of dementia (BPSD). The present study aimed to clarify the effects of YKS on learning and memory impairments, and its mechanisms of action in olfactory bulbectomized (OBX) mice, one of the animal models of Alzheimer's disease (AD). OBX or sham-operated ddY mice were treated with YKS or donepezil (DPZ), a reference drug, and their cognitive performances were tested by the modified Y-maze test, novel object recognition test, and fear conditioning test to elucidate the spatial working memory, non-spatial short-term memory, and long-term memory, respectively. After completing the behavioral experiments, the expression level of cholinergic marker proteins and the activity of acetylcholinesterase (AChE) in the brain were analyzed by western blotting and Ellman's method, respectively. OBX caused spatial working memory and non-spatial working memory impairments that were reversed by YKS and also by DPZ; however, YKS failed to affect the long-term memory deficits. Amelioration of the spatial working memory by YKS was reversible by scopolamine, a muscarinic receptor antagonist. YKS treatment reversed OBX-induced down-regulation of choline acetyltransferase and muscarinic muscarinic M₁ receptor expression without affecting muscarinic M₃ receptor expression or AChE activity. These results demonstrate that YKS improves short-term memory deficit caused by OBX and that the effect is at least partly mediated by muscarinic receptor stimulation and the normalization of central cholinergic systems. The present findings also suggest that YKS has a therapeutic effect not only on BPSD, but also on memory impairment of AD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  2. Persistent spatial working memory deficits in rats with bilateral cortical microgyria

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    Rosen Glenn D

    2008-10-01

    Full Text Available Abstract Background Anomalies of cortical neuronal migration (e.g., microgyria (MG and/or ectopias are associated with a variety of language and cognitive deficits in human populations. In rodents, postnatal focal freezing lesions lead to the formation of cortical microgyria similar to those seen in human dyslexic brains, and also cause subsequent deficits in rapid auditory processing similar to those reported in human language impaired populations. Thus convergent findings support the ongoing study of disruptions in neuronal migration in rats as a putative model to provide insight on human language disability. Since deficits in working memory using both verbal and non-verbal tasks also characterize dyslexic populations, the present study examined the effects of neonatally induced bilateral cortical microgyria (MG on working memory in adult male rats. Methods A delayed match-to-sample radial water maze task, in which the goal arm was altered among eight locations on a daily basis, was used to assess working memory performance in MG (n = 8 and sham (n = 10 littermates. Results Over a period of 60 sessions of testing (each session comprising one pre-delay sample trial, and one post-delay test trial, all rats showed learning as evidenced by a significant decrease in overall test errors. However, MG rats made significantly more errors than shams during initial testing, and this memory deficit was still evident after 60 days (12 weeks of testing. Analyses performed on daily error patterns showed that over the course of testing, MG rats utilized a strategy similar to shams (but with less effectiveness, as indicated by more errors. Conclusion These results indicate persistent abnormalities in the spatial working memory system in rats with induced disruptions of neocortical neuronal migration.

  3. Autobiographical and episodic memory deficits in mild traumatic brain injury.

    Science.gov (United States)

    Wammes, Jeffrey D; Good, Tyler J; Fernandes, Myra A

    2017-02-01

    Those who have suffered a concussion, otherwise known as a mild traumatic brain injury (mTBI), often complain of lingering memory problems. However, there is little evidence in the behavioral literature reliably demonstrating memory deficits. Thus, in the present study, cognitive profiles including measures of general executive functioning and processing speed, as well as episodic and semantic memory were collected in younger and older adult participants with or without a remote (>1year prior to testing) mTBI. We first investigated whether there were observable episodic and autobiographical memory impairments associated with mTBI within an otherwise healthy young group. Next, because previous work had demonstrated some overlap in patterns of behavioral impairment in normally aging adults and younger adults with a history of mTBI (e.g. Ozen, Fernandes, Clark, & Roy, 2015), we sought to determine whether these groups displayed similar cognitive profiles. Lastly, we conducted an exploratory analysis to test whether having suffered an mTBI might exacerbate age-related cognitive decline. Results showed the expected age-related decline in episodic memory performance, coupled with a relative preservation of semantic memory in older adults. Importantly, this pattern was also present in younger adults with a history of remote mTBI. No differences were observed across older adult groups based on mTBI status. Logistic regression analyses, using each measure in our battery as a predictor, successfully classified mTBI status in younger participants with a high degree of specificity (79.5%). These results indicate that those who have had an mTBI demonstrate a distinct cognitive signature, characterized by impairment in episodic and autobiographical memory, coupled with a relative preservation of semantic memory. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Impact of Education on Memory Deficits in Subclinical Depression.

    Science.gov (United States)

    McLaren, Molly E; Szymkowicz, Sarah M; Kirton, Joshua W; Dotson, Vonetta M

    2015-08-01

    Elevated depressive symptoms are associated with cognitive deficits, while higher education protects against cognitive decline. This study was conducted to test if education level moderates the relationship between depressive symptoms and cognitive function. Seventy-three healthy, dementia-free adults aged 18-81 completed neuropsychological tests, as well as depression and anxiety questionnaires. Controlling for age, sex, and state anxiety, we found a significant interaction of depressive symptoms and education for immediate and delayed verbal memory, such that those with a higher education level performed well regardless of depressive symptomatology, whereas those with lower education and high depressive symptoms had worse performance. No effects were found for executive functioning or processing speed. Results suggest that education protects against verbal memory deficits in individuals with elevated depressive symptoms. Further research on cognitive reserve in depression-related cognitive deficits and decline is needed to understand the mechanisms behind this phenomenon. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Beneficial effects of garlic on learning and memory deficits and brain tissue damages induced by lead exposure during juvenile rat growth is comparable to the effect of ascorbic acid.

    Science.gov (United States)

    Ghasemi, Simagol; Hosseini, Mahmoud; Feizpour, Azadeh; Alipour, Fatemeh; Sadeghi, Akram; Vafaee, Farzaneh; Mohammadpour, Toktam; Soukhtanloo, Mohammad; Ebrahimzadeh Bideskan, Alireza; Beheshti, Farimah

    2017-04-01

    The neuroprotective effects of both garlic and ascorbic acid (AA) have been documented. In this study the effects of garlic and ascorbic acid on memory deficits and brain tissue oxidative damages induced by lead exposure was investigated. The juvenile rats were divided and treated: (1) Control, (2) Lead (lead acetate in drinking water, 8 weeks), (3) Lead - Ascorbic Acid (Lead-AA), (4)  Lead - Garlic (100 mg/kg, daily, gavage) (Lead-Gar). In Morris water maze (MWM), the escape latency and traveled path in the Lead group were significantly higher while, the time spent in the target quadrant (Q1) was lower than Control. Both Lead-Gar and Lead-AA groups spent more times in Q1than to lead group. There were no significant differences in swimming speed between the groups. In passive avoidance (PA) test, the time latency for entering the dark compartment by Lead group was lower than Control. Treatment of the animals by AA and garlic significantly increased the time latency. In Lead group, the total thiol concentration in brain tissues was significantly lower while, MDA was higher than Control. Treatment by both garlic and AA increased total thiol concentrations and decreased MDA. Both garlic and AA decreased the lead content of brain tissues. It is suggested that treatment with garlic attenuates the learning and memory impairments due to lead exposure during juvenile rat growth which is comparable to AA. The possible mechanism may be due to its protective effects against brain tissues oxidative damage as well the lowering effects of brain lead content.

  6. cAMP/PKA-CREB-BDNF signaling pathway in hippocampus mediates cyclooxygenase 2-induced learning/memory deficits of rats subjected to chronic unpredictable mild stress.

    Science.gov (United States)

    Luo, Ying; Kuang, Shengnan; Li, Huan; Ran, Dongzhi; Yang, Junqing

    2017-05-30

    To investigate the mechanism of cyclooxygenase 2 (COX2) in learning and memory impairments in rats subjected to chronic unpredictable mild stress (CUMS), meloxicam was used intragastrically to inhibit the activity of cyclooxygenase 2. Moreover, cyclooxygenase 2 over-expressing or RNA interfere lentivirus was injected intraventricularly to increase or decrease the enzyme's expression, respectively. The body weights and sucrose consumption were used to analyze depressive behaviors, while the Morris water maze and step-down-type passive avoidance tests were carried out to evaluate the learning-memory functions. The levels of inflammatory cytokines were measured to estimate inflammation and the contents of cyclic adenosine monophosphate (cAMP) were used to measure the levels of the second messenger. Changes in cyclooxygenase 2 mRNA levels were analyzed using reverse transcription polymerase chain reaction. Moreover, the expression of cyclooxygenase 2, brain-derived neurotrophic factor (BDNF), prostaglandins receptor 3 (EP3), protein kinase A (PKA), cAMP response element binding protein (CREB), and phosphorylated CREB were estimated using immunohistochemical staining or western blotting. The results showed that CUMS led to significant depressive-like behaviors and learning and memory dysfunctions. Also, the cAMP levels decreased significantly, while levels of inflammatory cytokines and prostaglandins E2 increased significantly. The expressions of PKA, BDNF, phosphorylated CREB/CREB declined and cyclooxygenase 2 was increased. Meloxicam and cyclooxygenase 2 RNA interfere lentivirus reversed the changes caused by CUMS while cyclooxygenase 2-overexpressing lentivirus worsened these abnormalities. The findings also showed that CUMS increased cyclooxygenase 2 expression, which can cause learning and memory impairments, mainly through activating the hippocampal neuronal cAMP/PKA-CREB-BDNF signaling pathways.

  7. Elevations of endogenous kynurenic acid produce spatial working memory deficits.

    Science.gov (United States)

    Chess, Amy C; Simoni, Michael K; Alling, Torey E; Bucci, David J

    2007-05-01

    Kynurenic acid (KYNA) is a tryptophan metabolite that is synthesized and released by astrocytes and acts as a competitive antagonist of the glycine site of N-methyl-D-aspartate receptors at high concentrations and as a noncompetitive antagonist of the alpha7-nicotinic acetylcholine receptor at low concentrations. The discovery of increased cortical KYNA levels in schizophrenia prompted the hypothesis that elevated KYNA concentration may underlie the working memory dysfunction observed in this population that has been attributed to altered glutamatergic and/or cholinergic transmission. The present study investigated the effect of elevated endogenous KYNA on spatial working memory function in rats. Increased KYNA levels were achieved with intraperitoneal administration of kynurenine (100 mg/kg), the precursor of KYNA synthesis. Rats were treated with either kynurenine or a vehicle solution prior to testing in a radial arm maze task at various delays. Elevations of endogenous KYNA resulted in increased errors in the radial arm maze. In separate experiments, assessment of locomotor activity in an open field and latency to retrieve food reward from one of the maze arms ruled out the possibility that deficits in the maze were attributable to altered locomotor activity or motivation to consume food. These results provide evidence that increased KYNA levels produce spatial working memory deficits and are among the first to demonstrate the influence of glia-derived molecules on cognitive function. The implications for psychopathological conditions such as schizophrenia are discussed.

  8. Verbal Memory Deficits Are Correlated with Prefrontal Hypometabolism in 18FDG PET of Recreational MDMA Users

    Science.gov (United States)

    Bosch, Oliver G.; Wagner, Michael; Jessen, Frank; Kühn, Kai-Uwe; Joe, Alexius; Seifritz, Erich; Maier, Wolfgang; Biersack, Hans-Jürgen; Quednow, Boris B.

    2013-01-01

    Introduction 3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a recreational club drug with supposed neurotoxic effects selectively on the serotonin system. MDMA users consistently exhibit memory dysfunction but there is an ongoing debate if these deficits are induced mainly by alterations in the prefrontal or mediotemporal cortex, especially the hippocampus. Thus, we investigated the relation of verbal memory deficits with alterations of regional cerebral brain glucose metabolism (rMRGlu) in recreational MDMA users. Methods Brain glucose metabolism in rest was assessed using 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography (18FDG PET) in 19 male recreational users of MDMA and 19 male drug-naïve controls. 18FDG PET data were correlated with memory performance assessed with a German version of the Rey Auditory Verbal Learning Test. Results As previously shown, MDMA users showed significant impairment in verbal declarative memory performance. PET scans revealed significantly decreased rMRGlu in the bilateral dorsolateral prefrontal and inferior parietal cortex, bilateral thalamus, right hippocampus, right precuneus, right cerebellum, and pons (at the level of raphe nuclei) of MDMA users. Among MDMA users, learning and recall were positively correlated with rMRGlu predominantly in bilateral frontal and parietal brain regions, while recognition was additionally related to rMRGlu in the right mediotemporal and bihemispheric lateral temporal cortex. Moreover, cumulative lifetime dose of MDMA was negatively correlated with rMRGlu in the left dorsolateral and bilateral orbital and medial PFC, left inferior parietal and right lateral temporal cortex. Conclusions Verbal learning and recall deficits of recreational MDMA users are correlated with glucose hypometabolism in prefrontal and parietal cortex, while word recognition was additionally correlated with mediotemporal hypometabolism. We conclude that memory deficits of MDMA users arise from combined

  9. Follow-up study of memory deficits after ECT.

    Science.gov (United States)

    Shellenberger, W; Miller, M J; Small, I F; Milstein, V; Stout, J R

    1982-06-01

    Twenty-four patients received ECT induced by either alternating sine wave or brief pulsed-square wave stimulus and were evaluated at follow-up for clinical functioning and subjective memory loss. The hypothesis of less memory loss in the group receiving a weaker stimulus (pulsed-square wave) was not supported. The two treatment groups and a group of controls showed no significant differences on the memory test. On measures of clinical functioning the sine wave group scored better on every measure than the square wave group, although not significantly better.

  10. Organizational Learning Strategies and Verbal Memory Deficits in Bipolar Disorder.

    Science.gov (United States)

    Nitzburg, George C; Cuesta-Diaz, Armando; Ospina, Luz H; Russo, Manuela; Shanahan, Megan; Perez-Rodriguez, Mercedes; Larsen, Emmett; Mulaimovic, Sandra; Burdick, Katherine E

    2017-04-01

    Verbal memory (VM) impairment is prominent in bipolar disorder (BD) and is linked to functional outcomes. However, the intricacies of VM impairment have not yet been studied in a large sample of BD patients. Moreover, some have proposed VM deficits that may be mediated by organizational strategies, such as semantic or serial clustering. Thus, the exact nature of VM break-down in BD patients is not well understood, limiting remediation efforts. We investigated the intricacies of VM deficits in BD patients versus healthy controls (HCs) and examined whether verbal learning differences were mediated by use of clustering strategies. The California Verbal Learning Test (CVLT) was administered to 113 affectively stable BD patients and 106 HCs. We compared diagnostic groups on all CVLT indices and investigated whether group differences in verbal learning were mediated by clustering strategies. Although BD patients showed significantly poorer attention, learning, and memory, these indices were only mildly impaired. However, BD patients evidenced poorer use of effective learning strategies and lower recall consistency, with these indices falling in the moderately impaired range. Moreover, relative reliance on semantic clustering fully mediated the relationship between diagnostic category and verbal learning, while reliance on serial clustering partially mediated this relationship. VM deficits in affectively stable bipolar patients were widespread but were generally mildly impaired. However, patients displayed inadequate use of organizational strategies with clear separation from HCs on semantic and serial clustering. Remediation efforts may benefit from education about mnemonic devices or "chunking" techniques to attenuate VM deficits in BD. (JINS, 2017, 23, 358-366).

  11. Rehabilitation in severe memory deficit: A case study

    Directory of Open Access Journals (Sweden)

    Nariana Mattos Figueiredo Sousa

    Full Text Available ABSTRACT The term amnesia refers to a pathological state of mind in which memory and learning are affected to a greater extent than other cognitive functions in a patient without altered level of consciousness. The aim of the current study was to describe a case of severe amnesia in a patient during neurological rehabilitation and to report the importance of preserved cognitive functions to compensate for the mnemonic deficit. VJA presented a clinical condition suggestive of encephalopathy due to caloric-protein malnutrition following several abdominal surgical procedures for complicated choledocholithiasis. A descriptive analysis of the results was carried out to outline the goals attained and the factors limiting implementation of memory aids. After the intervention program, consisting of individual and group activities, VJA showed improvement in level of recall with repetition of tasks, but still required constant external monitoring. Longitudinal follow-up is necessary to obtain more consistent results.

  12. Allocentric spatial learning and memory deficits in Down syndrome.

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    Pamela A Banta Lavenex

    2015-02-01

    Full Text Available Studies have shown that persons with Down Syndrome (DS exhibit relatively poor language capacities, and impaired verbal and visuoperceptual memory, whereas their visuospatial memory capacities appear comparatively spared. Individuals with DS recall better where an object was previously seen than what object was previously seen. However, most of the evidence concerning preserved visuospatial memory comes from tabletop or computerized experiments which are biased towards testing egocentric (viewpoint-dependent spatial representations. Accordingly, allocentric (viewpoint-independent spatial learning and memory capacities may not be necessary to perform these tasks. Thus, in order to more fully characterize the spatial capacities of individuals with DS, allocentric processes underlying real-world navigation must also be investigated. We tested 20 participants with DS and 16 mental age-matched, typically developing (TD children in a real-world, allocentric spatial memory task. During local cue (LC trials, participants had to locate three rewards marked by local color cues, among 12 locations distributed in a 4 m X 4 m arena. During allocentric spatial (AS trials, participants had to locate the same three rewards, in absence of local cues, based on their relations to distal environmental cues. All TD participants chose rewarded locations in LC and AS trials at above chance level. In contrast, although all but one of the participants with DS exhibited a preference for the rewarded locations in LC trials, only 50% of participants with DS chose the rewarded locations at above chance level in AS trials. As a group, participants with DS performed worse than TD children on all measures of task performance. These findings demonstrate that individuals with DS are impaired at using an allocentric spatial representation to learn and remember discrete locations in a controlled environment, suggesting persistent and pervasive deficits in hippocampus

  13. Bombesin administration impairs memory and does not reverse memory deficit caused by sleep deprivation.

    Science.gov (United States)

    Ferreira, L B T; Oliveira, S L B; Raya, J; Esumi, L A; Hipolide, D C

    2017-07-28

    Sleep deprivation impairs performance in emotional memory tasks, however this effect on memory is not completely understood. Possible mechanisms may involve an alteration in neurotransmission systems, as shown by the fact that many drugs that modulate neural pathways can prevent memory impairment by sleep loss. Gastrin releasing peptide (GRP) is a neuropeptide that emerged as a regulatory molecule of emotional memory through the modulation of other neurotransmission systems. Thus, the present study addressed the effect of intraperitoneal (IP) administration of bombesin (BB) (2.5, 5.0 and 10.0μg/kg), a GRP agonist, on the performance of Wistar rats in a multiple trail inhibitory avoidance (MTIA) task, after sleep deprivation, using the modified multiple platforms method (MMPM). Sleep deprived animals exhibited acquisition and retention impairment that was not prevented by BB injection. In addition, non-sleep deprived animals treated with BB before and after the training session, but not before the test, have shown a retention deficit. In summary, BB did not improve the memory impairment by sleep loss and, under normal conditions, produced a memory consolidation deficit. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Kuboyama, Tomoharu; Hirotsu, Keisuke; Arai, Tetsuya; Yamasaki, Hiroo; Tohda, Chihiro

    2017-01-01

    Memory impairments in Alzheimer's disease (AD) occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia ; PR) is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract) was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid β (Aβ) plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aβ plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aβ. Additionally, it prevented Aβ-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aβ-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.

  15. A High-Fructose-High-Coconut Oil Diet Induces Dysregulating Expressions of Hippocampal Leptin and Stearoyl-CoA Desaturase, and Spatial Memory Deficits in Rats.

    Science.gov (United States)

    Lin, Ching-I; Shen, Chu-Fu; Hsu, Tsui-Han; Lin, Shyh-Hsiang

    2017-06-16

    We investigated the effects of high-fructose-high-fat diets with different fat compositions on metabolic parameters, hippocampal-dependent cognitive function, and brain leptin (as well as stearoyl-CoA desaturase (SCD1) mRNA expressions). Thirty-two male Wistar rats were divided into 3 groups, a control group ( n = 8), a high-fructose soybean oil group (37.5% of fat calories, n = 12), and a high-fructose coconut oil group (37.5% of fat calories, n = 12) for 20 weeks. By the end of the study, the coconut oil group exhibited significantly higher serum fasting glucose, fructosamine, insulin, leptin, and triglyceride levels compared to those of the control and soybean oil groups. However, hippocampal leptin expression and leptin receptor mRNA levels were significantly lower, while SCD1 mRNA was significantly higher in rats fed the high-fructose-high-coconut oil diet than in rats fed the other experimental diets. In addition, the coconut oil group spent significantly less time in the target quadrant on the probe test in the Morris water maze (MWM) task. Rats fed the high-fructose-high-coconut oil diet for 20 weeks were prone to develop hyperglycemia, hyperinsulinemia, hyperleptinemia, and hypertriglyceridemia. These metabolic consequences may contribute to hippocampal-dependent memory impairment, accompanied by a lower central leptin level, and a higher SCD1 gene expression in the brain.

  16. Simulating episodic memory deficits in semantic dementia with the TraceLink model

    NARCIS (Netherlands)

    Meeter, M.; Murre, J.M.J.

    2004-01-01

    Although semantic dementia is primarily characterised by deficits in semantic memory, episodic memory is also impaired. Patients show poor recall of old autobiographical and semantic memories, with better retrieval of recent experiences; they can form new memories, and normal performance on

  17. Chronic administration of quercetin prevent spatial learning and memory deficits provoked by chronic stress in rats.

    Science.gov (United States)

    Mohammadi, Hadis Said; Goudarzi, Iran; Lashkarbolouki, Taghi; Abrari, Kataneh; Elahdadi Salmani, Mahmoud

    2014-08-15

    There are several reports that cognitive impairment is observed in stress related disorders and chronic stress impairs learning and memory. However, very few studies have looked into the possible ways of preventing this stress-induced deficit. This research study was conducted to evaluate the effects of quercetin, a natural flavonoid, with strong antioxidant and free radical scavenger properties, on chronic stress induced learning and memory deficits and oxidative stress in hippocampus. For chronic stress, rats were restrained daily for 6h/day (from 9:00 to 15:00) for 21 days in well-ventilated plexiglass tubes without access to food and water. The animals were injected with quercetin or vehicle 60 min before restraint stress over a period of 21 days. Then, rats trained with six trials per day for 6 consecutive days in the water maze. On day 28, a probe test was done to measure memory retention. In addition, oxidative stress markers in the hippocampus were evaluated. Results of this study demonstrated that chronic stress exposure rats exhibited higher escape latency during training trials and reduced time spent in target quadrant, higher escape location latency and average proximity in probe trial test. Quercetin (50mg/kg) treatment during restraint stress (21 days) markedly decreased escape latency and increased time spent in target quadrant during Morris water maze task. In comparison to vehicle treated group, chronic-stress group had significantly higher malondialdehyde (MDA) levels, significantly higher superoxide dismutase (SOD) activity and significantly lower glutathione peroxidase (GPx) activity in the hippocampus. Quercetin treatment caused a significant decrease in the hippocampus MDA levels and improves SOD and GPx activities in stressed animals. Finally, quercetin significantly decreased plasma corticosterone levels in stressed animals. Based on results of this study, chronic stress has detrimental effects on learning and memory and quercetin treatment

  18. Choline reverses scopolamine-induced memory impairment by improving memory reconsolidation.

    Science.gov (United States)

    Blake, M G; Boccia, M M; Krawczyk, M C; Delorenzi, A; Baratti, C M

    2012-09-01

    It is widely known that pre-training systemic administration of the muscarinic antagonist scopolamine (SCP) (0.5mg/kg, i.p.) leads to anterograde memory impairment in retention tests. The administration of the α(7)-nicotinic receptor agonist choline (Ch) in the dorsal hippocampus (0.8μg/hippocampus) immediately after memory reactivation allowed recovery from scopolamine-induced memory impairment. This effect of Ch was time-dependent, and retention performance was not affected in drug-treated mice that were not subjected to memory reactivation, suggesting that the performance effects are not due to non-specific effects of the drug. The effects of Ch also depended on the age of the reactivated memory. Altogether, our results suggest that Ch exerts its effects by modulating memory reconsolidation, and that the memory impairment induced by low doses of SCP is a memory expression failure and not a storage deficit. Therefore, reconsolidation, among other functions, might serve to change memory expression in later tests. Summarizing, our results open new avenues about the behavioral significance and the physiological functions of memory reconsolidation, providing new strategies for recovering memories from some types of amnesia. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1

    Science.gov (United States)

    Havekes, Robbert; Park, Alan J; Tudor, Jennifer C; Luczak, Vincent G; Hansen, Rolf T; Ferri, Sarah L; Bruinenberg, Vibeke M; Poplawski, Shane G; Day, Jonathan P; Aton, Sara J; Radwańska, Kasia; Meerlo, Peter; Houslay, Miles D; Baillie, George S; Abel, Ted

    2016-01-01

    Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density. DOI: http://dx.doi.org/10.7554/eLife.13424.001 PMID:27549340

  20. Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1.

    Science.gov (United States)

    Havekes, Robbert; Park, Alan J; Tudor, Jennifer C; Luczak, Vincent G; Hansen, Rolf T; Ferri, Sarah L; Bruinenberg, Vibeke M; Poplawski, Shane G; Day, Jonathan P; Aton, Sara J; Radwańska, Kasia; Meerlo, Peter; Houslay, Miles D; Baillie, George S; Abel, Ted

    2016-08-23

    Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density.

  1. Working Memory Deficits in Boys with Attention-Deficit/Hyperactivity Disorder (ADHD): The Contribution of Central Executive and Subsystem Processes

    Science.gov (United States)

    Rapport, Mark D.; Alderson, R. Matt; Kofler, Michael J.; Sarver, Dustin E.; Bolden, Jennifer; Sims, Valerie

    2008-01-01

    The current study investigated contradictory findings from recent experimental and meta-analytic studies concerning working memory deficits in ADHD. Working memory refers to the cognitive ability to temporarily store and mentally manipulate limited amounts of information for use in guiding behavior. Phonological (verbal) and visuospatial…

  2. Experimental sleep deprivation as a tool to test memory deficits in rodents

    Directory of Open Access Journals (Sweden)

    VALERIA eCOLAVITO

    2013-12-01

    Full Text Available Paradigms of sleep deprivation (SD and memory testing in rodents (laboratory rats and mice are here reviewed. The vast majority of these studies have been aimed at understanding the contribution of sleep to cognition, and in particular to memory. Relatively little attention, instead, has been devoted to SD as a challenge to induce a transient memory impairment, and therefore as a tool to test cognitive enhancers in drug discovery. The purpose of this article is to provide an overview of the studies that have accurately described methodological aspects of the SD protocol and behavioral paradigm in order to critically assess them and propose SD protocols that could be employed as cognitive challenge. Total SD, partial or state-selective SD (rapid eye movement SD procedures are first reviewed, followed by procedures to investigate SD-induced impairment of learning and memory consolidation. Thus, a platform of knowledge is here provided for laboratory protocols that could be used to assess the efficacy of drugs designed to improve memory performance in rodents, including rodent models of neurodegenerative diseases that cause cognitive deficits, and Alzheimer’s disease in particular. Issues in the interpretation of such preclinical data and their predictive value for clinical translation are also discussed.

  3. Experimental sleep deprivation as a tool to test memory deficits in rodents

    Science.gov (United States)

    Colavito, Valeria; Fabene, Paolo F.; Grassi-Zucconi, Gigliola; Pifferi, Fabien; Lamberty, Yves; Bentivoglio, Marina; Bertini, Giuseppe

    2013-01-01

    Paradigms of sleep deprivation (SD) and memory testing in rodents (laboratory rats and mice) are here reviewed. The vast majority of these studies have been aimed at understanding the contribution of sleep to cognition, and in particular to memory. Relatively little attention, instead, has been devoted to SD as a challenge to induce a transient memory impairment, and therefore as a tool to test cognitive enhancers in drug discovery. Studies that have accurately described methodological aspects of the SD protocol are first reviewed, followed by procedures to investigate SD-induced impairment of learning and memory consolidation in order to propose SD protocols that could be employed as cognitive challenge. Thus, a platform of knowledge is provided for laboratory protocols that could be used to assess the efficacy of drugs designed to improve memory performance in rodents, including rodent models of neurodegenerative diseases that cause cognitive deficits, and Alzheimer's disease in particular. Issues in the interpretation of such preclinical data and their predictive value for clinical translation are also discussed. PMID:24379759

  4. Beneficial effects of TQRF and TQ nano- and conventional emulsions on memory deficit, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble Aβ levels in high fat-cholesterol diet-induced rats.

    Science.gov (United States)

    Ismail, Norsharina; Ismail, Maznah; Azmi, Nur Hanisah; Bakar, Muhammad Firdaus Abu; Yida, Zhang; Stanslas, Johnson; Sani, Dahiru; Basri, Hamidon; Abdullah, Maizaton Atmadini

    2017-09-25

    The study determined the effect of thymoquinone rich fraction (TQRF) and thymoquinone (TQ) in the forms of nano- and conventional emulsions on learning and memory, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble β-amyloid (Aβ) levels in rats fed with a high fat-cholesterol diet (HFCD). The TQRF was extracted from Nigella sativa seeds using a supercritical fluid extraction system and prepared into nanoemulsion, which later named as TQRF nanoemulsion (TQRFNE). Meanwhile, TQ was acquired commercially and prepared into thymoquinone nanoemulsion (TQNE). The TQRF and TQ conventional emulsions (CE), named as TQRFCE and TQCE, respectively were studied for comparison. Statin (simvastatin) and non-statin (probucol) cholesterol-lowering agents, and a mild-to-severe Alzheimer's disease drug (donepezil) were served as control drugs. The Sprague Dawley rats were fed with HFCD for 6 months, and treated with the intervention groups via oral gavage daily for the last 3 months. As a result, HFCD-fed rats exhibited hypercholesterolaemia, accompanied by memory deficit, increment of lipid peroxidation and soluble Aβ levels, decrement of total antioxidant status and down-regulation of antioxidants genes expression levels. TQRFNE demonstrated comparable effects to the other intervention groups and control drugs in serum biomarkers as well as in the learning and memory test. Somehow, TQRFNE was more prominent than those intervention groups and control drugs in brain biomarkers concomitant to gene and protein expression levels. Supplementation of TQRFNE into an HFCD thus could ameliorate memory deficit, lipid peroxidation and soluble Aβ levels as well as improving the total antioxidant status and antioxidants genes expression levels. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Methylphenidate Improves Visual-Spatial Memory in Children with Attention-Deficit- hyperactivity Disorder

    Science.gov (United States)

    Bedard, Anne-Claude; Martinussen, Rhonda; Ickowicz, Abel; Tannock, Rosemary

    2004-01-01

    Objective: To investigate the effect of methylphenidate (MPH) on visual-spatial memory, as measured by subtests of the Cambridge Neuropsychological Testing Automated Battery (CANTAB), in children with attention-deficit/hyperactivity disorder (ADHD). Visual-spatial memory is a core component of working memory that has been shown to be impaired in…

  6. Naringin ameliorates cognitive deficits in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Xianchu Liu

    2016-04-01

    Full Text Available Objective(s:Previous research demonstrated that diabetes is one of the leading causes of learning and memory deficits. Naringin, a bioflavonoid isolated from grapefruits and oranges, has potent protective effects on streptozotocin (STZ-induced diabetic rats. Recently, the effects of naringin on learning and memory performances were monitored in many animal models of cognitive impairment. However, to date, no studies have investigated the ameliorative effects of naringin on diabetes-associated cognitive decline (DACD. In this study, we investigated the effects of naringin, using a STZ-injected rat model and explored its potential mechanism. Materials and Methods:Diabetic rats were treated with naringin (100 mg/kg/d for 7 days. The learning and memory function were assessed by Morris water maze test. The oxidative stress indicators [superoxide dismutase (SOD and malondialdehyde (MDA] and inflammatory cytokines (TNF-a, IL-1β, and IL-6 were measured in hippocampus using corresponding commercial kits. The mRNA and protein levels of PPARγ were evaluated by real time (RT-PCR and Western blot analysis. Results:The results showed that supplementation of naringin improved learning and memory performances compared with the STZ group. Moreover, naringin supplement dramatically increased SOD levels, reduced MDA levels, and alleviated TNF-α, IL-1β, and IL-6 compared with the STZ group in the hippocampus. The pretreatment with naringin also significantly increased PPARγ expression. Conclusion: Our results showed that naringin may be a promising therapeutic agent for improving cognitive decline in DACD.

  7. 5-HT6 receptor antagonist attenuates the memory deficits associated with neuropathic pain and improves the efficacy of gabapentinoids.

    Science.gov (United States)

    Jayarajan, Pradeep; Nirogi, Ramakrishna; Shinde, Anil; Goura, Venkatesh; Babu, Vuyyuru Arun; Yathavakilla, Sumanth; Bhyrapuneni, Gopinadh

    2015-10-01

    Memory deficit is a co-morbid disorder in patients suffering from neuropathic pain. Gabapentin and pregabalin (gabapentinoids) are among the widely prescribed medications for the treatment of neuropathic pain. Memory loss and sedation are the commonly reported side effects with gabapentinoids. Improving the cognitive functions and attenuating drug-induced side effects may play a crucial role in the management of pain. We evaluated the effects of 5-HT6 receptor antagonists on the memory deficits associated with neuropathy. We also studied the effects of 5-HT6 receptor antagonists on the side effects, and the analgesic effects of gabapentinoids. 5-HT6 receptor antagonists attenuated the cognitive deficits in neuropathic rats. Neuropathic rats co-treated with 5-HT6 receptor antagonist and gabapentinoids showed improvement in memory. 5-HT6 receptor antagonists enhanced the analgesic effects of gabapentinoids but had no effect on the motor side effects. The observed effects may not be due to pharmacokinetic interactions. 5-HT6 receptor antagonist attenuate the cognitive deficits associated with neuropathy, and this effect is also seen when co-treated with gabapentinoids. Since, 5-HT6 antagonists improved the effectiveness of gabapentinoids, reduction in the dosage and frequency of gabapentinoids treatment may reduce the side effects. Combining 5-HT6 receptor antagonist with gabapentinoids may offer a novel treatment strategy for neuropathic pain. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  8. Loss of perforated synapses in the dentate gyrus: morphological substrate of memory deficit in aged rats.

    Science.gov (United States)

    Geinisman, Y; de Toledo-Morrell, L; Morrell, F

    1986-01-01

    Most, but not all, aged rats exhibit a profound deficit in spatial memory when tested in a radial maze--a task known to depend on the integrity of the hippocampal formation. In this study, animals were divided into three groups based on their spatial memory capacity: young adult rats with good memory, aged rats with impaired memory, and aged rats with good memory. Memory-impaired aged animals showed a loss of perforated axospinous synapses in the dentate gyrus of the hippocampal formation in comparison with either young adults or aged rats with good memory. This finding suggests that the loss of perforated axospinous synapses in the hippocampal formation underlies the age-related deficit in spatial memory. Images PMID:3458260

  9. Retinoic Acid Restores Adult Hippocampal Neurogenesis and Reverses Spatial Memory Deficit in Vitamin A Deprived Rats

    Science.gov (United States)

    Alfos, Serge; Pallet, Véronique; Higueret, Paul; Abrous, Djoher Nora

    2008-01-01

    A dysfunction of retinoid hippocampal signaling pathway has been involved in the appearance of affective and cognitive disorders. However, the underlying neurobiological mechanisms remain unknown. Hippocampal granule neurons are generated throughout life and are involved in emotion and memory. Here, we investigated the effects of vitamin A deficiency (VAD) on neurogenesis and memory and the ability of retinoic acid (RA) treatment to prevent VAD-induced impairments. Adult retinoid-deficient rats were generated by a vitamin A-free diet from weaning in order to allow a normal development. The effects of VAD and/or RA administration were examined on hippocampal neurogenesis, retinoid target genes such as neurotrophin receptors and spatial reference memory measured in the water maze. Long-term VAD decreased neurogenesis and led to memory deficits. More importantly, these effects were reversed by 4 weeks of RA treatment. These beneficial effects may be in part related to an up-regulation of retinoid-mediated molecular events, such as the expression of the neurotrophin receptor TrkA. We have demonstrated for the first time that the effect of vitamin A deficient diet on the level of hippoccampal neurogenesis is reversible and that RA treatment is important for the maintenance of the hippocampal plasticity and function. PMID:18941534

  10. Retinoic acid restores adult hippocampal neurogenesis and reverses spatial memory deficit in vitamin A deprived rats.

    Directory of Open Access Journals (Sweden)

    Emilie Bonnet

    Full Text Available A dysfunction of retinoid hippocampal signaling pathway has been involved in the appearance of affective and cognitive disorders. However, the underlying neurobiological mechanisms remain unknown. Hippocampal granule neurons are generated throughout life and are involved in emotion and memory. Here, we investigated the effects of vitamin A deficiency (VAD on neurogenesis and memory and the ability of retinoic acid (RA treatment to prevent VAD-induced impairments. Adult retinoid-deficient rats were generated by a vitamin A-free diet from weaning in order to allow a normal development. The effects of VAD and/or RA administration were examined on hippocampal neurogenesis, retinoid target genes such as neurotrophin receptors and spatial reference memory measured in the water maze. Long-term VAD decreased neurogenesis and led to memory deficits. More importantly, these effects were reversed by 4 weeks of RA treatment. These beneficial effects may be in part related to an up-regulation of retinoid-mediated molecular events, such as the expression of the neurotrophin receptor TrkA. We have demonstrated for the first time that the effect of vitamin A deficient diet on the level of hippoccampal neurogenesis is reversible and that RA treatment is important for the maintenance of the hippocampal plasticity and function.

  11. Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Tomoharu Kuboyama

    2017-11-01

    Full Text Available Memory impairments in Alzheimer’s disease (AD occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia; PR is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid β (Aβ plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aβ plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aβ. Additionally, it prevented Aβ-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aβ-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.

  12. Memory deficits due to brain injury: unique PET findings and dream alterations

    OpenAIRE

    Nishida, Masaki; Nariai, Tadashi; Hiura, Mikio; Ishii, Kenji; Nishikawa, Toru

    2011-01-01

    The authors herein report the case of a young male with memory deficits due to a traumatic head injury, who presented with sleep-related symptoms such as hypersomnia and dream alterations. Although MRI and polysomnography showed no abnormalities, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and 11C flumazenil (FMZ)-PET revealed findings consistent with cerebral damage to the affected temporal region. The memory deficit of the patient gradually improved in parallel with the re...

  13. Learning Difficulties and Working Memory Deficits among Primary School Students in Jakarta, Indonesia

    OpenAIRE

    Wiguna, Tjhin; Setyawati WR, Noorhana; Kaligis, Fransiska; Belfer, Myron Lowell

    2012-01-01

    Objective: There are multiple possible etiologies for learning difficulties in children. There is growing evidence that many students identified as having learning difficulties have significant working memory deficits. To determine, in a sample of primary school students in Jakarta, Indonesia, the prevalence of learning difficulties and learning difficulties co-morbid with working memory deficits. Methods: Subjects (N=423) were recruited via proportional random sampling from 27 primary school...

  14. Social isolation induces deficit of latent learning performance in mice: a putative animal model of attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Ouchi, Hirofumi; Ono, Kazuya; Murakami, Yukihisa; Matsumoto, Kinzo

    2013-02-01

    Social isolation of rodents (SI) elicits a variety of stress responses such as increased aggressiveness, hyper-locomotion, and reduced susceptibility to pentobarbital. To obtain a better understanding of the relevance of SI-induced behavioral abnormalities to psychiatric disorders, we examined the effect of SI on latent learning as an index of spatial attention, and discussed the availability of SI as an epigenetic model of attention deficit hyperactivity disorder (ADHD). Except in specially stated cases, 4-week-old male mice were housed in a group or socially isolated for 3-70 days before experiments. The animals socially isolated for 1 week or more exhibited spatial attention deficit in the water-finding test. Re-socialized rearing for 5 weeks after 1-week SI failed to attenuate the spatial attention deficit. The effect of SI on spatial attention showed no gender difference or correlation with increased aggressive behavior. Moreover, SI had no effect on cognitive performance elucidated in a modified Y-maze or an object recognition test, but it significantly impaired contextual and conditional fear memory elucidated in the fear-conditioning test. Drugs used for ADHD therapy, methylphenidate (1-10 mg/kg, i.p.) and caffeine (0.5-1 mg/kg, i.p.), improved SI-induced latent learning deficit in a manner reversible with cholinergic but not dopaminergic antagonists. Considering the behavioral features of SI mice together with their susceptibility to ADHD drugs, the present findings suggest that SI provides an epigenetic animal model of ADHD and that central cholinergic systems play a role in the effect of methylphenidate on SI-induced spatial attention deficit. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Memory Deficits in Schizophrenia: A Selective Review of Functional Magnetic Resonance Imaging (fMRI Studies

    Directory of Open Access Journals (Sweden)

    Adrienne C. Lahti

    2013-06-01

    Full Text Available Schizophrenia is a complex chronic mental illness that is characterized by positive, negative and cognitive symptoms. Cognitive deficits are most predictive of long-term outcomes, with abnormalities in memory being the most robust finding. The advent of functional magnetic resonance imaging (fMRI has allowed exploring neural correlates of memory deficits in vivo. In this article, we will give a selective review of fMRI studies probing brain regions and functional networks that are thought to be related to abnormal memory performance in two memory systems prominently affected in schizophrenia; working memory and episodic memory. We revisit the classic “hypofrontality” hypothesis of working memory deficits and explore evidence for frontotemporal dysconnectivity underlying episodic memory abnormalities. We conclude that fMRI studies of memory deficits in schizophrenia are far from universal. However, the current literature does suggest that alterations are not isolated to a few brain regions, but are characterized by abnormalities within large-scale brain networks.

  16. A Meta-Analysis of Working Memory Impairments in Children with Attention-Deficit/hyperactivity Disorder.

    Science.gov (United States)

    Martinussen, Rhonda; Hayden, Jill; Hogg-Johnson, Sheilah; Tannock, Rosemary

    2005-01-01

    Objective: To determine the empirical evidence for deficits in working memory (WM) processes in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: Exploratory meta-analytic procedures were used to investigate whether children with ADHD exhibit WM impairments. Twenty-six empirical research studies published from…

  17. Neural correlates of visuospatial working memory in attention-deficit/hyperactivity disorder and healthy controls

    NARCIS (Netherlands)

    Ewijk, H. van; Weeda, W.D.; Heslenfeld, D.J.; Luman, M.; Hartman, C.A.; Hoekstra, P.J.; Faraone, S.V.; Franke, B.; Buitelaar, J.K.; Oosterlaan, J.

    2015-01-01

    Impaired visuospatial working memory (VSWM) is suggested to be a core neurocognitive deficit in attention-deficit/hyperactivity disorder (ADHD), yet the underlying neural activation patterns are poorly understood. Furthermore, it is unclear to what extent age and gender effects may play a role in

  18. Learning Difficulties and Working Memory Deficits among Primary School Students in Jakarta, Indonesia.

    Science.gov (United States)

    Wiguna, Tjhin; Setyawati Wr, Noorhana; Kaligis, Fransiska; Belfer, Myron L

    2012-08-01

    There are multiple possible etiologies for learning difficulties in children. There is growing evidence that many students identified as having learning difficulties have significant working memory deficits. To determine, in a sample of primary school students in Jakarta, Indonesia, the prevalence of learning difficulties and learning difficulties co-morbid with working memory deficits. Subjects (N=423) were recruited via proportional random sampling from 27 primary schools. The first stage was a cross-sectional study of these students, while the second stage was a case-control study comparing all students with learning difficulties and working memory deficits with controls matched by school type, grade level, and gender. Among the students, whose mean age was 9.34 years (1.78), 13.7% had a learning difficulty, while 8.04% had a learning difficulty with working memory deficit. The odds ratio of comorbid working memory deficit (in the face of a learning difficulty) was 7.0 (χ(2)= 35.96, pLearning difficulties and comorbid working memory deficits were relatively common among primary school students. Efforts should be made to identify these students and provide timely assistance, in order to optimize their educational success and mental health outcomes.

  19. Involvement of opioid system in cognitive deficits induced by ∆⁹-tetrahydrocannabinol in rats.

    Science.gov (United States)

    Egashira, Nobuaki; Manome, Naomi; Mishima, Kenichi; Iwasaki, Katsunori; Oishi, Ryozo; Fujiwara, Michihiro

    2012-02-01

    Cannabis is a widely used illicit substance. ∆(9)-Tetrahydrocannabinol (THC), the major psychoactive component of cannabis, is known to induce cognitive deficits that closely resemble the impairment observed in schizophrenic patients. We previously reported that THC (6 mg/kg) impairs spatial memory in the eight-arm radial maze, and that this memory disturbance was reversed by the cannabinoid CB(1) receptor antagonist rimonabant (0.1 mg/kg), suggesting that the effect of THC is mediated through cannabinoid CB(1) receptors. The present study was designed to examine the possible involvement of opioid receptors in the THC-induced impairment of spatial memory. The effects of treatment with the nonselective opioid receptor antagonist naloxone (0.3 and 1 mg/kg), the μ-opioid receptor antagonist β-funaltrexamine (0.3 and 1 mg/kg), the δ-opioid receptor antagonist naltrindole (1 and 3 mg/kg), and the κ-opioid receptor antagonist nor-binaltorphimine (0.03 and 0.1 mg/kg) on the impairment of spatial memory induced by THC were evaluated using the eight-arm radial maze. The nonselective opioid receptor antagonist naloxone, the μ-opioid receptor antagonist β-funaltrexamine, and the κ-opioid receptor antagonist nor-binaltorphimine, but not the δ-opioid receptor antagonist naltrindole, attenuated THC-induced cognitive deficits, suggesting an involvement of μ- and κ-opioid receptors in this behavioral response. These results demonstrate that the endogenous opioid system is involved in the regulation of the acute short-term and working memory deficits induced by cannabis.

  20. Short-Term Memory Limitations in Children: Capacity or Processing Deficits?

    Science.gov (United States)

    Chi, Michelene T. H.

    1976-01-01

    Evaluates the assertion that short-term memory (STM) capacity increases with age and concludes that the STM capacity limitation in children is due to the deficits in the processing strategies and speeds, which presumably improve with age through cumulative learning. (JM) Available from: Memory and Cognition, Psychonomic Society, 1018 West 34…

  1. Visual working memory and number sense : Testing the double deficit hypothesis in mathematics

    NARCIS (Netherlands)

    Toll, Sylke; Kroesbergen, Evelyn; Van Luit, Johannes E H

    2016-01-01

    Background: Evidence exists that there are two main underlying cognitive factors in mathematical difficulties: working memory and number sense. It is suggested that real math difficulties appear when both working memory and number sense are weak, here referred to as the double deficit (DD)

  2. Emerging Depression Is Associated with Face Memory Deficits in Adolescent Girls

    Science.gov (United States)

    Guyer, Amanda E.; Choate, Victoria R.; Grimm, Kevin J.; Pine, Daniel S.; Keenan, Kate

    2011-01-01

    Objective: To examine the association between memory for previously encoded emotional faces and depression symptoms assessed over 4 years in adolescent girls. Investigating the interface between memory deficits and depression in adolescent girls may provide clues about depression pathophysiology. Method: Participants were 213 girls recruited from…

  3. Learning and Memory Impairments in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Andersen, Per N.; Egeland, Jens; Øie, Merete

    2013-01-01

    There are relatively few studies on learning and delayed memory with attention-deficit/hyperactivity disorder (ADHD). The objective of the present study was to examine acquisition, free delayed memory, and recognition skills in medication naive children and adolescents aged 8-16 years with ADHD combined subtype (36 participants) and inattentive…

  4. Visual Working Memory and Number Sense: Testing the Double Deficit Hypothesis in Mathematics

    Science.gov (United States)

    Toll, Sylke W. M.; Kroesbergen, Evelyn H.; Van Luit, Johannes E. H.

    2016-01-01

    Background: Evidence exists that there are two main underlying cognitive factors in mathematical difficulties: working memory and number sense. It is suggested that real math difficulties appear when both working memory and number sense are weak, here referred to as the double deficit (DD) hypothesis. Aims: The aim of this study was to test the DD…

  5. Deficit of the "primacy effect" in parkinsonians interpreted by means of the working memory model.

    Science.gov (United States)

    Della Sala, S; Pasetti, C; Sempio, P

    1987-01-01

    29 Parkinsonians and 29 controls matched for age and schooling were tested for memory by means of a free recall test (serial position curve) and two spans (verbal and non-verbal). The free recall test yields three measures: primacy (item 1); secondary memory (items 2-7) and recency (items 8-12). The Parkinsonians displayed a selective deficit of primacy, which is taken to be evidence of defective functioning of the Central Executive in the Working Memory model.

  6. Visual short-term memory deficits in REM sleep behaviour disorder mirror those in Parkinson's disease.

    Science.gov (United States)

    Rolinski, Michal; Zokaei, Nahid; Baig, Fahd; Giehl, Kathrin; Quinnell, Timothy; Zaiwalla, Zenobia; Mackay, Clare E; Husain, Masud; Hu, Michele T M

    2016-01-01

    Individuals with REM sleep behaviour disorder are at significantly higher risk of developing Parkinson's disease. Here we examined visual short-term memory deficits--long associated with Parkinson's disease--in patients with REM sleep behaviour disorder without Parkinson's disease using a novel task that measures recall precision. Visual short-term memory for sequentially presented coloured bars of different orientation was assessed in 21 patients with polysomnography-proven idiopathic REM sleep behaviour disorder, 26 cases with early Parkinson's disease and 26 healthy controls. Three tasks using the same stimuli controlled for attentional filtering ability, sensorimotor and temporal decay factors. Both patients with REM sleep behaviour disorder and Parkinson's disease demonstrated a deficit in visual short-term memory, with recall precision significantly worse than in healthy controls with no deficit observed in any of the control tasks. Importantly, the pattern of memory deficit in both patient groups was specifically explained by an increase in random responses. These results demonstrate that it is possible to detect the signature of memory impairment associated with Parkinson's disease in individuals with REM sleep behaviour disorder, a condition associated with a high risk of developing Parkinson's disease. The pattern of visual short-term memory deficit potentially provides a cognitive marker of 'prodromal' Parkinson's disease that might be useful in tracking disease progression and for disease-modifying intervention trials. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

  7. Rg3-enriched ginseng extract ameliorates scopolamine-induced learning deficits in mice.

    Science.gov (United States)

    Kim, Jiyoung; Shim, Jaesung; Lee, Siyoung; Cho, Woo-Hyun; Hong, Eunyoung; Lee, Jin Hee; Han, Jung-Soo; Lee, Hyong Joo; Lee, Ki Won

    2016-02-18

    Ginseng (Panax ginseng C.A. Meyer) has been used as a traditional herb in the treatment of many medical disorders. Ginsenosides, which are triterpene derivatives that contain sugar moieties, are the main pharmacological ingredients in ginseng. This study was designed to investigate the effect of ginsenoside Rg3-enriched ginseng extract (Rg3GE) on scopolamine-induced memory impairment in mice. Rg3GE (50 and 100 mg/kg) were administered to C57BL/6 mice by oral gavage for 14 days (days 1-14). Memory impairment was induced by scopolamine (1 mg/kg, intraperitoneal injection) for 6 days (days 914). The Morris water maze test was used to assess hippocampus-dependent spatial memory. The effects of scopolamine with or without Rg3GE on acetylcholinesterase and nuclear factor-κB (NF-κB) in the hippocampus were also examined. Mice with scopolamine treatment alone showed impairments in the acquisition and retention of spatial memory. Mice that received Rg3GE and scopolamine showed no scopolamine-induced impairment in the acquisition of spatial memory. Oral administration of Rg3GE suppressed the scopolamine-mediated increase in acetylcholinesterase activity and stimulation of the NF-κB pathway (i.e., phosphorylation of p65) in the hippocampus. These findings suggest that Rg3GE may stabilize scopolamine-induced memory deficits through the inhibition of acetylcholinesterase activity and NF-κB signaling in the hippocampus.

  8. A flavanoid component of chocolate quickly reverses an imposed memory deficit.

    Science.gov (United States)

    Knezevic, Bogdan; Komatsuzaki, Yoshimasa; de Freitas, Emily; Lukowiak, Ken

    2016-03-01

    The ability to remember is influenced by environmental and lifestyle factors, such as stress and diet. A flavanol contained in chocolate, epicatechin (Epi), has been shown to enhance long-term memory (LTM) formation in Lymnaea. Combining two stressors (low-calcium pond water and crowding) blocks learning and all forms of memory; that is, this combination of environmentally relevant stressors creates a memory-unfriendly state. We tested the hypothesis that Epi will immediately reverse the memory-unfriendly state, i.e. that snails in the memory-deficit state when trained in Epi will immediately become competent to learn and form memory. We found that Epi not only reverses the memory-deficit state but also further enhances LTM formation. Thus, a naturally occurring bioactive plant compound can overcome a memory-unfriendly state. This supports the idea that bioactive substances may mitigate memory-making deficits that, for example, occur with ageing. © 2016. Published by The Company of Biologists Ltd.

  9. Dissociation of working memory impairments and attention-deficit/hyperactivity disorder in the brain

    Directory of Open Access Journals (Sweden)

    Aaron T. Mattfeld

    2016-01-01

    Full Text Available Prevailing neuropsychological models of attention-deficit/hyperactivity disorder (ADHD propose that ADHD arises from deficits in executive functions such as working memory, but accumulating clinical evidence suggests a dissociation between ADHD and executive dysfunctions. This study examined whether ADHD and working memory capacity are behaviorally and neurobiologically separable using functional magnetic resonance imaging (fMRI. Participants diagnosed with ADHD in childhood who subsequently remitted or persisted in their diagnosis as adults were characterized at follow-up in adulthood as either impaired or unimpaired in spatial working memory relative to controls who never had ADHD. ADHD participants with impaired spatial working memory performed worse than controls and ADHD participants with unimpaired working memory during an n-back working memory task while being scanned. Both controls and ADHD participants with unimpaired working memory exhibited significant linearly increasing activation in the inferior frontal junction, precuneus, lingual gyrus, and cerebellum as a function of working-memory load, and these activations did not differ significantly between these groups. ADHD participants with impaired working memory exhibited significant hypoactivation in the same regions, which was significantly different than both control participants and ADHD participants with unimpaired working memory. These findings support both a behavioral and neurobiological dissociation between ADHD and working memory capacity.

  10. Dissociation of working memory impairments and attention-deficit/hyperactivity disorder in the brain.

    Science.gov (United States)

    Mattfeld, Aaron T; Whitfield-Gabrieli, Susan; Biederman, Joseph; Spencer, Thomas; Brown, Ariel; Fried, Ronna; Gabrieli, John D E

    2016-01-01

    Prevailing neuropsychological models of attention-deficit/hyperactivity disorder (ADHD) propose that ADHD arises from deficits in executive functions such as working memory, but accumulating clinical evidence suggests a dissociation between ADHD and executive dysfunctions. This study examined whether ADHD and working memory capacity are behaviorally and neurobiologically separable using functional magnetic resonance imaging (fMRI). Participants diagnosed with ADHD in childhood who subsequently remitted or persisted in their diagnosis as adults were characterized at follow-up in adulthood as either impaired or unimpaired in spatial working memory relative to controls who never had ADHD. ADHD participants with impaired spatial working memory performed worse than controls and ADHD participants with unimpaired working memory during an n-back working memory task while being scanned. Both controls and ADHD participants with unimpaired working memory exhibited significant linearly increasing activation in the inferior frontal junction, precuneus, lingual gyrus, and cerebellum as a function of working-memory load, and these activations did not differ significantly between these groups. ADHD participants with impaired working memory exhibited significant hypoactivation in the same regions, which was significantly different than both control participants and ADHD participants with unimpaired working memory. These findings support both a behavioral and neurobiological dissociation between ADHD and working memory capacity.

  11. Osthole Improves Spatial Memory Deficits in Rats via Hippocampal α1-Adrenergic and D1/D2 Receptors

    Directory of Open Access Journals (Sweden)

    Li-Wei Lin

    2013-01-01

    Full Text Available The present study evaluated the effect of osthole, an active ingredient isolated from Cnidium monnieri L. Cusson, on spatial memory deficits caused by central neurotoxins using the Morris water maze in rats. The involvement of catecholaminergic receptors on the memory-enhancing effect of osthole in rat hippocampus was further investigated by intrahippocampal injection of catecholaminergic receptor antagonists. Intracisternal injection of osthole (10 μg/brain improved the spatial performance and working memory impairments caused by the catecholaminergic neurotoxin 6-hydroxydopamine. No significant differences in swimming speeds were observed among sham, neurotoxin-induced, and osthole-treated groups. Intracisternal osthole injection also attenuated the spatial performance and working memory impairments caused by the α1 receptor antagonist phenoxybenzamine, the D1 receptor antagonist SCH 23390, and the D2 receptor antagonist sulpiride. Therefore, we demonstrated that the effect of osthole on improving spatial memory deficits may be related to the activation of hippocampal α1 and D1/D2 receptors.

  12. Diphenyl diselenide improves scopolamine-induced memory impairment in mice.

    Science.gov (United States)

    Souza, Ana Cristina G; Brüning, César Augusto; Leite, Marlon Régis; Zeni, Gilson; Nogueira, Cristina Wayne

    2010-09-01

    This study was conducted to evaluate the effects of exposure to diphenyl diselenide (PhSe)2 on cognitive impairment induced by scopolamine, a muscarinic antagonist, using the Y-maze and Morris water maze tests in mice. One hour before the tests, mice were treated with (PhSe)2 (50 mg/kg, oral) and 30 min later memory impairment was induced by administration of scopolamine (1 mg/kg, intraperitoneal). (PhSe)2 (50 mg/kg, oral) significantly improved scopolamine-induced memory impairment in the Y-maze test. At the probe trial session in Morris water maze, (PhSe)2 (50 mg/kg, oral) significantly decreased the escape latency, increased the number of crossings in the platform local, and increased the time spent in the platform quadrant when compared with the scopolamine-treated group. General locomotor activity was similar in all groups. This study showed that (PhSe)2 ameliorated the impairments of spatial long-term memory and short-term memory, showed by the performance of mice in the Morris water maze and Y-maze tasks, respectively. These results suggest that (PhSe)2 may be useful for the treatment of cognitive impairment that may hold significant therapeutic value in alleviating certain memory deficits observed in Alzheimer's disease.

  13. AMPA receptors mediate passive avoidance deficits induced by sleep deprivation.

    Science.gov (United States)

    Dubiela, Francisco Paulino; Queiroz, Claudio Marcos; Moreira, Karin Di Monteiro; Nobrega, Jose N; Sita, Luciane Valéria; Tufik, Sergio; Hipolide, Debora Cristina

    2013-11-15

    The present study addressed the effects of sleep deprivation (SD) on AMPA receptor (AMPAR) binding in brain regions associated with learning and memory, and investigated whether treatment with drugs acting on AMPAR could prevent passive avoidance deficits in sleep deprived animals. [(3)H]AMPA binding and GluR1 in situ hybridization signals were quantified in different brain regions of male Wistar rats either immediately after 96 h of sleep deprivation or after 24h of sleep recovery following 96 h of sleep deprivation. Another group of animals were sleep deprived and then treated with either the AMPAR potentiator, aniracetam (25, 50 and 100mg/kg, acute administration) or the AMPAR antagonist GYKI-52466 (5 and 10mg/kg, acute and chronic administration) before passive avoidance training. Task performance was evaluated 2h and 24h after training. A significant reduction in [(3)H]AMPA binding was found in the hippocampal formation of SD animals, while no alterations were observed in GluR1 mRNA levels. The highest dose of aniracetam (100mg/kg) reverted SD-induced impairment of passive avoidance performance in both retention tests, whereas GYKI-52466 treatment had no effect. Pharmacological enhancement of AMPAR function may revert hippocampal-dependent learning impairments produced after SD. We argue that such effects might be associated with reduced AMPAR binding in the hippocampus of sleep deprived animals. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Biflorin Ameliorates Memory Impairments Induced by Cholinergic Blockade in Mice

    Science.gov (United States)

    Jeon, Se Jin; Kim, Boseong; Ryu, Byeol; Kim, Eunji; Lee, Sunhee; Jang, Dae Sik; Ryu, Jong Hoon

    2017-01-01

    To examine the effect of biflorin, a component of Syzygium aromaticum, on memory deficit, we introduced a scopolamine-induced cognitive deficit mouse model. A single administration of biflorin increased latency time in the passive avoidance task, ameliorated alternation behavior in the Y-maze, and increased exploration time in the Morris water maze task, indicating the improvement of cognitive behaviors against cholinergic dysfunction. The biflorin-induced reverse of latency in the scopolamine-treated group was attenuated by MK-801, an NMDA receptor antagonist. Biflorin also enhanced cognitive function in a naïve mouse model. To understand the mechanism of biflorin for memory amelioration, we performed Western blot. Biflorin increased the activation of protein kinase C-ζ and its downstream signaling molecules in the hippocampus. These results suggest that biflorin ameliorates drug-induced memory impairment by modulation of protein kinase C-ζ signaling in mice, implying that biflorin could function as a possible therapeutic agent for the treatment of cognitive problems. PMID:27829270

  15. Neuroprotective effects of 20(S)-protopanaxatriol (PPT) on scopolamine-induced cognitive deficits in mice.

    Science.gov (United States)

    Lu, Cong; Lv, Jingwei; Dong, Liming; Jiang, Ning; Wang, Yan; Wang, Qiong; Li, Yinghui; Chen, Shanguang; Fan, Bei; Wang, Fengzhong; Liu, Xinmin

    2018-02-22

    20(S)-protopanaxatriol (PPT), one of the ginsenosides from Panax ginseng, has been reported to have neuroprotective effects and to improve memory. The present study was designed to investigate the protective effect of PPT on scopolamine-induced cognitive deficits in mice. Male Institute of Cancer Research mice were pretreated with 2 different doses of PPT (20 and 40 μmol/kg) for 27 days by intraperitoneal injection, and scopolamine (0.75 mg/kg) was injected intraperitoneally for 9 days to induce memory impairment. Thirty minutes after the last pretreatment, the locomotor activity was firstly examined to evaluate the motor function of mice. Then, memory-related behaviors were evaluated, and the related mechanism was further researched. It was founded that PPT treatment significantly reversed scopolamine-induced cognitive impairment in the object location recognition experiment, the Morris water maze test, and the passive avoidance task, showing memory-improving effects. PPT also significantly improved cholinergic system reactivity and suppressed oxidative stress, indicated by inhibition of acetylcholinesterase activity, elevation of acetylcholine levels, increasing superoxide dismutase activity and lowering levels of malondialdehyde in the hippocampus. In addition, the expression levels of Egr-1, c-Jun, and cAMP responsive element binding in the hippocampus were significantly elevated by PPT administration. These results suggest that PPT may be a potential drug candidate for the treatment of cognitive deficit in Alzheimer's disease. Copyright © 2018 John Wiley & Sons, Ltd.

  16. Modafinil ameliorates cognitive deficits induced by maternal separation and sleep deprivation.

    Science.gov (United States)

    Garcia, Vanessa Athaíde; Hirotsu, Camila; Matos, Gabriela; Alvarenga, Tathiana; Pires, Gabriel Natan; Kapczinski, Flávio; Schröder, Nadja; Tufik, Sergio; Andersen, Monica Levy

    2013-09-15

    Animals exposed to an early adverse event may be more susceptible to a second source of stress later in life, and these stressors may have additive deleterious effects. Sleep deprivation is known to be a stressor, affecting multiple body functions such as the cognition. Modafinil enhances working memory and attention in healthy non-sleep deprived subjects and in animal models of sleep deprivation. The first aim of the present study was to investigate the effects of maternal separation (MS) combined with paradoxical sleep deprivation (PSD) in adulthood on recognition memory in rats. Second, we aimed to evaluate whether the administration of modafinil would be able to ameliorate memory deficits induced by MS and PSD. Wistar rat pups were initially distributed into MS and handling (H) groups, with their litters standardized in 4 females and 4 males. In adulthood, the male rats were submitted to PSD or control condition, being redistributed afterwards in modafinil- or vehicle-treatment immediately after the training session of object recognition task. PSD did not potentiate the cognitive deficit due to MS. However, modafinil was able to recover memory impairments associated to PSD and also to MS in the neonatal period. This study demonstrates for the first time that modafinil ameliorates cognitive deficits associated to MS and to PSD in adulthood, independent from MS in the neonatal period. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Recollection of Emotional Memories in Schizophrenia: Autonoetic awareness and specificity deficits

    Directory of Open Access Journals (Sweden)

    Aurore Neumann

    2006-03-01

    Full Text Available Episodic memory impairments seem to play a crucial role in schizophrenia. Most of the studies that have demonstrated such a deficit have used neutral material, leaving the recollection of emotional memories in schizophrenia unexplored. An overview is presented of a series of studies investigating the influence of emotion on episodic and autobiographical memory in schizophrenia. These experiments share a common experimental approach in which states of awareness accompanying recollection are considered. Results show that schizophrenia impairs conscious recollection in episodic and autobiographical memory tasks using emotional material. Schizophrenia is also associated with a reduction of the specificity with which autobiographical memories are recalled. An hypothesis in terms of a fundamental executive deficit underlying these impairments is proposed.

  18. Age-related binding deficits and the content of false memories.

    Science.gov (United States)

    Lyle, Keith B; Bloise, Suzanne M; Johnson, Marcia K

    2006-03-01

    The authors examined effects of age-related binding deficits on feature information in false memories for imagined objects (e.g., lollipop) that were similar in shape to seen objects (e.g., magnifying glass). In Experiment 1, location memory for seen objects was lower in older than younger adults and lower still in old-old than young-old adults. Imagined objects, when falsely called seen, were less likely to be attributed to the location of similar seen objects (i.e., congruent attributions) by old-old than young-old adults. In Experiment 2, for younger adults, displaying seen objects for less time (1 s vs. 4 s) reduced both location memory for seen objects and congruent attributions for false memories. Thus, binding deficits may influence the specific content of false memories. ((c) 2006 APA, all rights reserved).

  19. Exploring the Effects of Working Memory on Time Perception in Attention Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Lee, Hom-Yi; Yang, En-Lin

    2018-01-01

    Children with attention deficit hyperactivity disorder (ADHD) are often reported to have deficits of time perception. However, there is a strong relation between performance on tasks of working memory and time perception. Thus, it is possible that the poor performance of children with ADHD on time perception results from their deficit of working memory. In this study, the working memory of participants was separately assessed; therefore, we could explore the relationship between working memory and time perception of children with ADHD. Fifty-six children with ADHD and those of healthy controls completed tasks measuring working memory and time perception. The results showed that the time discrimination ability of children with ADHD was poorer than that of controls. However, there was a strong association between time perception and working memory. After controlling working memory and intelligence, the time discrimination ability of children with ADHD was not significantly poorer than that of controls. We suggest that there is an interdependent relationship between time perception and working memory for children with ADHD.

  20. Early postnatal nociceptive stimulation results in deficits of spatial memory in male rats.

    Science.gov (United States)

    Amaral, Cristiane; Antonio, Bruno; Oliveira, Maria Gabriela Menezes; Hamani, Clement; Guinsburg, Ruth; Covolan, Luciene

    2015-11-01

    Prematurely-born infants are exposed to multiple invasive procedures while in the intensive care unit. Newborn rats and humans have similar behavioral responses to noxious stimulation. Previous studies have shown that early noxious stimuli may alter dentate gyrus neurogenesis and the behavioral repertoire of adult rats. We evaluated the late effects of noxious stimulation administered during different phases of development on two spatial memory tests; object recognition (OR) and Morris water maze (WM) tests. Noxious stimulation was induced by an intra-plantar injection of complete Freund's adjuvant (CFA) on postnatal (P) day 1 (group P1) or 8 (P8). Control animals were not stimulated. Behavioral tests were conducted on P60 in both male and female animals. In the WM, three domains were evaluated: acquisition, probe trial performance and reversal re-acquisition. The number of Nissl stained cells in the dentate granule cell layer was assessed by stereological counting. The OR test revealed that P1 male rats had poor long-term memory compared to the control and P8 groups. In the WM, no short- or long-term memory differences were detected between early postnatal-stimulated male and female rats and their respective controls. However, the ability to find the hidden platform in a new position was reduced in P1 male rats. The number of dentate granule cells in P8 males was higher than in all other groups. This study demonstrates that noxious stimulation on P1 results in spatial learning deficits in male animals, but does not disrupt the development of the hippocampus-dependent strategies of learning and memory. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Impaired pitch perception and memory in congenital amusia: the deficit starts in the auditory cortex.

    Science.gov (United States)

    Albouy, Philippe; Mattout, Jérémie; Bouet, Romain; Maby, Emmanuel; Sanchez, Gaëtan; Aguera, Pierre-Emmanuel; Daligault, Sébastien; Delpuech, Claude; Bertrand, Olivier; Caclin, Anne; Tillmann, Barbara

    2013-05-01

    Congenital amusia is a lifelong disorder of music perception and production. The present study investigated the cerebral bases of impaired pitch perception and memory in congenital amusia using behavioural measures, magnetoencephalography and voxel-based morphometry. Congenital amusics and matched control subjects performed two melodic tasks (a melodic contour task and an easier transposition task); they had to indicate whether sequences of six tones (presented in pairs) were the same or different. Behavioural data indicated that in comparison with control participants, amusics' short-term memory was impaired for the melodic contour task, but not for the transposition task. The major finding was that pitch processing and short-term memory deficits can be traced down to amusics' early brain responses during encoding of the melodic information. Temporal and frontal generators of the N100m evoked by each note of the melody were abnormally recruited in the amusic brain. Dynamic causal modelling of the N100m further revealed decreased intrinsic connectivity in both auditory cortices, increased lateral connectivity between auditory cortices as well as a decreased right fronto-temporal backward connectivity in amusics relative to control subjects. Abnormal functioning of this fronto-temporal network was also shown during the retention interval and the retrieval of melodic information. In particular, induced gamma oscillations in right frontal areas were decreased in amusics during the retention interval. Using voxel-based morphometry, we confirmed morphological brain anomalies in terms of white and grey matter concentration in the right inferior frontal gyrus and the right superior temporal gyrus in the amusic brain. The convergence between functional and structural brain differences strengthens the hypothesis of abnormalities in the fronto-temporal pathway of the amusic brain. Our data provide first evidence of altered functioning of the auditory cortices during pitch

  2. Memory functioning in children with reading disabilities and/or attention deficit/hyperactivity disorder: a clinical investigation of their working memory and long-term memory functioning.

    Science.gov (United States)

    Kibby, Michelle Y; Cohen, Morris J

    2008-11-01

    We examined memory functioning in children with reading disabilities (RD), Attention deficit/hyperactivity disorder (ADHD), and RD/ADHD using a clinic sample with a clinical instrument: the Children's Memory Scale, enhancing its generalizability. Participants included 23 children with RD, 30 with ADHD, 30 with RD/ADHD, and 30 controls. Children with RD presented with reduced verbal short-term memory (STM) but intact visual STM, central executive (CE), and long-term memory (LTM) functioning. Their deficit in STM appeared specific to tasks requiring phonetic coding of material. Children with ADHD displayed intact CE and LTM functioning but reduced visual-spatial STM, especially when off stimulant medication. Children with RD/ADHD had deficits consistent with both disorders.

  3. Behavioral analysis of NR2C knockout mouse reveals deficit in acquisition of conditioned fear and working memory.

    Science.gov (United States)

    Hillman, Brandon G; Gupta, Subhash C; Stairs, Dustin J; Buonanno, Andres; Dravid, Shashank M

    2011-05-01

    N-methyl-D-aspartate (NMDA) receptors play an important role in excitatory neurotransmission and mediate synaptic plasticity associated with learning and memory. NMDA receptors are composed of two NR1 and two NR2 subunits and the identity of the NR2 subunit confers unique electrophysiologic and pharmacologic properties to the receptor. The precise role of NR2C-containing receptors in vivo is poorly understood. We have performed a battery of behavioral tests on NR2C knockout/nβ-galactosidase knock-in mice and found no difference in spontaneous activity, basal anxiety, forced-swim immobility, novel object recognition, pain sensitivity and reference memory in comparison to wildtype counterparts. However, NR2C knockout mice were found to exhibit deficits in fear acquisition and working memory compared to wildtype mice. Deficit in fear acquisition correlated with lack of fear conditioning-induced plasticity at the thalamo-amygdala synapse. These findings suggest a unique role of NR2C-containing receptors in associative and executive learning representing a novel therapeutic target for deficits in cognition. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Memory deficits in long-term survivors of childhood brain tumors may primarily reflect general cognitive dysfunctions

    DEFF Research Database (Denmark)

    Reimers, Tonny Solveig; Mortensen, Erik Lykke; Schmiegelow, Kjeld

    2007-01-01

    To analyze the impact of potential predictors on memory performance in survivors of childhood brain tumors and to examine whether deficits in memory after radiotherapy (RT) should be considered part of a more global mental dysfunction.......To analyze the impact of potential predictors on memory performance in survivors of childhood brain tumors and to examine whether deficits in memory after radiotherapy (RT) should be considered part of a more global mental dysfunction....

  5. Progression of logopenic variant primary progressive aphasia to apraxia and semantic memory deficits

    Science.gov (United States)

    2013-01-01

    Background Due to the nature of neurodegenerative disorders, patients with primary progressive aphasia develop cognitive impairment other than aphasia as the disorder progresses. The progression of logopenic variant primary progressive aphasia (lvPPA), however, has not been well described. In particular, praxic disorders and semantic memory deficits have rarely been reported. Case presentations We report three patients in the initial stage of lvPPA who subsequently developed apraxia in the middle stage and developed clinically evident semantic memory deficits in the advanced stages. Conclusions The present case series suggests that some patients with lvPPA develop an atypical type of dementia with apraxia and semantic memory deficits, suggesting that these cases should be classified as a type of early-onset Alzheimer’s disease. PMID:24176108

  6. Is selective mutism associated with deficits in memory span and visual memory?: An exploratory case-control study.

    Science.gov (United States)

    Kristensen, Hanne; Oerbeck, Beate

    2006-01-01

    Our main aim in this study was to explore the association between selective mutism (SM) and aspects of nonverbal cognition such as visual memory span and visual memory. Auditory-verbal memory span was also examined. The etiology of SM is unclear, and it probably represents a heterogeneous condition. SM is associated with language impairment, but nonspecific neurodevelopmental factors, including motor problems, are also reported in SM without language impairment. Furthermore, SM is described in Asperger's syndrome. Studies on nonverbal cognition in SM thus merit further investigation. Neuropsychological tests were administered to a clinical sample of 32 children and adolescents with SM (ages 6-17 years, 14 boys and 18 girls) and 62 nonreferred controls matched for age, gender, and socioeconomic status. We used independent t-tests to compare groups with regard to auditory-verbal memory span, visual memory span, and visual memory (Benton Visual Retention Test), and employed linear regression analysis to study the impact of SM on visual memory, controlling for IQ and measures of language and motor function. The SM group differed from controls on auditory-verbal memory span but not on visual memory span. Controlled for IQ, language, and motor function, the SM group did not differ from controls on visual memory. Motor function was the strongest predictor of visual memory performance. SM does not appear to be associated with deficits in visual memory span or visual memory. The reduced auditory-verbal memory span supports the association between SM and language impairment. More comprehensive neuropsychological studies are needed.

  7. Working memory deficits in adults with ADHD: is there evidence for subtype differences?

    Directory of Open Access Journals (Sweden)

    Medoff Deborah R

    2006-12-01

    Full Text Available Abstract Background Working memory performance is important for maintaining functioning in cognitive, academic and social activities. Previous research suggests there are prevalent working memory deficits in children with attention deficit hyperactivity disorder (ADHD. There is now a growing body of literature characterizing working memory functioning according to ADHD subtypes in children. The expression of working memory deficits in adults with ADHD and how they vary according to subtype, however, remains to be more fully documented. Methods This study assessed differences in working memory functioning between Normal Control (NC adults (N = 18; patients with ADHD, Combined (ADHD-CT Type ADHD (N = 17; and ADHD, Inattentive (ADHD-IA Type (N = 16 using subtests from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-III and the Paced Auditory Serial Addition Task (PASAT. Results The ADHD groups displayed significant weaknesses in contrast to the NC group on working memory tests requiring rapid processing and active stimulus manipulation. This included the Letter-Number-Sequencing test of the Wechsler scales, PASAT omission errors and the longest sequence of consecutive correct answers on the PASAT. No overall ADHD group subtype differences emerged; however differences between the ADHD groups and the NC group varied depending on the measure and the gender of the participants. Gender differences in performance were evident on some measures of working memory, regardless of group, with males performing better than females. Conclusion In general, the data support a dimensional interpretation of working memory deficits experienced by the ADHD-CT and ADHD-IA subtypes, rather than an absolute difference between subtypes. Future studies should test the effects of processing speed and load on subtype performance and how those variables interact with gender in adults with ADHD.

  8. Working memory deficits in adults with ADHD: is there evidence for subtype differences?

    Science.gov (United States)

    Schweitzer, Julie B; Hanford, Russell B; Medoff, Deborah R

    2006-12-15

    Working memory performance is important for maintaining functioning in cognitive, academic and social activities. Previous research suggests there are prevalent working memory deficits in children with attention deficit hyperactivity disorder (ADHD). There is now a growing body of literature characterizing working memory functioning according to ADHD subtypes in children. The expression of working memory deficits in adults with ADHD and how they vary according to subtype, however, remains to be more fully documented. This study assessed differences in working memory functioning between Normal Control (NC) adults (N = 18); patients with ADHD, Combined (ADHD-CT) Type ADHD (N = 17); and ADHD, Inattentive (ADHD-IA) Type (N = 16) using subtests from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-III and the Paced Auditory Serial Addition Task (PASAT). The ADHD groups displayed significant weaknesses in contrast to the NC group on working memory tests requiring rapid processing and active stimulus manipulation. This included the Letter-Number-Sequencing test of the Wechsler scales, PASAT omission errors and the longest sequence of consecutive correct answers on the PASAT. No overall ADHD group subtype differences emerged; however differences between the ADHD groups and the NC group varied depending on the measure and the gender of the participants. Gender differences in performance were evident on some measures of working memory, regardless of group, with males performing better than females. In general, the data support a dimensional interpretation of working memory deficits experienced by the ADHD-CT and ADHD-IA subtypes, rather than an absolute difference between subtypes. Future studies should test the effects of processing speed and load on subtype performance and how those variables interact with gender in adults with ADHD.

  9. Deficits in episodic memory and mental time travel in patients with post-traumatic stress disorder.

    Science.gov (United States)

    Zlomuzica, Armin; Woud, Marcella L; Machulska, Alla; Kleimt, Katharina; Dietrich, Lisa; Wolf, Oliver T; Assion, Hans-Joerg; Huston, Joseph P; De Souza Silva, Maria A; Dere, Ekrem; Margraf, Jürgen

    2018-04-20

    Post-traumatic stress disorder (PTSD) is characterized by impairments in mnestic functions, especially in the domain of episodic memory. These alterations might affect different aspects of episodic memory functioning. Here we tested PTSD patients and healthy controls (matched for age, sex and education) in a newly developed virtual reality episodic memory test (VR-EMT), a test for mental time travel, episodic future thinking, and prospective memory (M3xT). In a cross-validation experiment, their performance was further evaluated in the Rivermead Behavioral Memory Test (RBMT). PTSD patients demonstrated impairments in episodic memory formation and mental time travel and showed difficulties in utilizing information from episodic memory to solve problems. Diminished attention and concentration in PTSD did not account for performance deficits in these tasks but higher levels of negative arousal were found in PTSD patients. Furthermore, performance in the VR-EMT and RBMT in PTSD patients correlated negatively with self-reported measures of stress and depression. Our results suggest that deficits in episodic memory formation and mental time travel in PTSD lead to difficulties in utilizing the content of episodic memories for solving problems in the present or to plan future behavior. Clinical implications of these findings and suggestions for cognitive-behavioral treatment of PTSD are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Autism-Like Behaviours and Memory Deficits Result from a Western Diet in Mice

    Directory of Open Access Journals (Sweden)

    Ekaterina Veniaminova

    2017-01-01

    Full Text Available Nonalcoholic fatty liver disease, induced by a Western diet (WD, evokes central and peripheral inflammation that is accompanied by altered emotionality. These changes can be associated with abnormalities in social behaviour, hippocampus-dependent cognitive functions, and metabolism. Female C57BL/6J mice were fed with a regular chow or with a WD containing 0.2% of cholesterol and 21% of saturated fat for three weeks. WD-treated mice exhibited increased social avoidance, crawl-over and digging behaviours, decreased body-body contacts, and hyperlocomotion. The WD-fed group also displayed deficits in hippocampal-dependent performance such as contextual memory in a fear conditioning and pellet displacement paradigms. A reduction in glucose tolerance and elevated levels of serum cholesterol and leptin were also associated with the WD. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1a mRNA, a marker of mitochondrial activity, was decreased in the prefrontal cortex, hippocampus, hypothalamus, and dorsal raphe, suggesting suppressed brain mitochondrial functions, but not in the liver. This is the first report to show that a WD can profoundly suppress social interactions and induce dominant-like behaviours in naïve adult mice. The spectrum of behaviours that were found to be induced are reminiscent of symptoms associated with autism, and, if paralleled in humans, suggest that a WD might exacerbate autism spectrum disorder.

  11. Memory deficits due to brain injury: unique PET findings and dream alterations.

    Science.gov (United States)

    Nishida, Masaki; Nariai, Tadashi; Hiura, Mikio; Ishii, Kenji; Nishikawa, Toru

    2011-12-01

    The authors herein report the case of a young male with memory deficits due to a traumatic head injury, who presented with sleep-related symptoms such as hypersomnia and dream alterations. Although MRI and polysomnography showed no abnormalities, (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and (11)C flumazenil (FMZ)-PET revealed findings consistent with cerebral damage to the affected temporal region. The memory deficit of the patient gradually improved in parallel with the relief of the sleep-related symptoms. FDG-PET showed considerable improvement in glucose metabolism when he had recovered, however, evidence of neural loss remained in the FMZ-PET findings.

  12. Visual memory-deficit amnesia: A distinct amnesic presentation and etiology

    OpenAIRE

    Rubin, David C.; Greenberg, Daniel L.

    1998-01-01

    We describe a form of amnesia, which we have called visual memory-deficit amnesia, that is caused by damage to areas of the visual system that store visual information. Because it is caused by a deficit in access to stored visual material and not by an impaired ability to encode or retrieve new material, it has the otherwise infrequent properties of a more severe retrograde than anterograde amnesia with no temporal gradient in the retrograde amnesia. Of the 11 cases of long-term visual memory...

  13. Verbal memory in drug-naive, newly diagnosed Parkinson's disease. The retrieval deficit hypothesis revisited.

    Science.gov (United States)

    Brønnick, Kolbjørn; Alves, Guido; Aarsland, Dag; Tysnes, Ole-Bjørn; Larsen, Jan Petter

    2011-01-01

    The retrieval deficit hypothesis on memory impairment in patients with Parkinson's disease (PD) implies a selective impairment in recall of learned material with normal encoding, retention, and recognition. This hypothesis has been challenged by new data. We have therefore investigated verbal memory and learning in a large sample of newly diagnosed, drug naïve, non-demented patients with PD. From a sample of patients with PD from the Norwegian ParkWest study, 133 PD patients and 133 controls matched on sex, age, and education were included. The California Verbal Learning Test-2 (CVLT-2) was used to assess verbal memory. Patients performed significantly worse than controls on free and cued recall as well as on recognition memory. Patients used the semantic clustering learning strategy significantly less extensively than the controls and the learning slope of the PD patients was significantly less steep. There was no difference in retention when controlling for encoding. Patients did not perform better on the recognition measure or on cued recall (d-prime), as compared to free recall. Executive functions explained a substantial part of the memory deficits. This study suggests that memory impairment in drug naïve early PD to a large degree is a deficit of learning/ encoding and not of retention or retrieval. An implication is that the retrieval deficit hypothesis should be moderated in its general form. Executive deficits and less extensive use of the efficient semantic clustering learning strategy had a strong impact on learning and memory. (c) 2010 APA, all rights reserved.

  14. Stimulant medications for attention-deficit/hyperactivity disorder (ADHD) improve memory of emotional stimuli in ADHD-diagnosed college students.

    Science.gov (United States)

    Maul, J; Advokat, C

    2013-04-01

    Stimulant medications do not improve the academic achievement of ADHD diagnosed undergraduates. One reason may be that stimulant-induced sympathetic arousal might impair memory. To test this hypothesis, we conducted a study between September 2011 and March 2012, to compare medicated (n=12) and non-medicated (n=11) ADHD diagnosed undergraduates, with non-ADHD students (n=12). All participants were presented with an audiovisual narrative that included an emotional segment, and answered questions about the story one week later. All groups remembered the emotional segment significantly better than the neutral segments. Non-medicated ADHD students recalled less of both segments than the medicated ADHD or non-ADHD groups, which did not differ from each other. Stimulants improved memory in ADHD students, and did not impair the relative retention of emotional, as opposed to neutral information. Stimulant-induced arousal cannot explain the academic deficit of ADHD undergraduates. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Sulforaphane alleviates scopolamine-induced memory impairment in mice.

    Science.gov (United States)

    Lee, Siyoung; Kim, Jisung; Seo, Sang Gwon; Choi, Bo-Ryoung; Han, Jung-Soo; Lee, Ki Won; Kim, Jiyoung

    2014-07-01

    Sulforaphane, an organosulfur compound present in cruciferous vegetables, has been shown to exert neuroprotective effects in experimental in vitro and in vivo models of neurodegeneration. To determine whether sulforaphane can preserve cognitive function, we examined its effects on scopolamine-induced memory impairment in mice using the Morris water maze test. Sulforaphane (10 or 50mg/kg) was administered to C57BL/6 mice by oral gavage for 14 days (days 1-14), and memory impairment was induced by intraperitoneal injection of scopolamine (1mg/kg) for 7 days (days 8-14). Mice that received scopolamine alone showed impaired learning and memory retention and considerably decreased cholinergic system reactivity in the hippocampus and frontal cortex, as indicated by a decreased acetylcholine (ACh) level and an increased acetylcholinesterase (AChE) activity. Sulforaphane significantly attenuated the scopolamine-induced memory impairment and improved cholinergic system reactivity, as indicated by an increased ACh level, decreased AChE activity, and increased choline acetyltransferase (ChAT) expression in the hippocampus and frontal cortex. These effects of sulforaphane on cholinergic system reactivity were confirmed in vitro. Sulforaphane (10 or 20μM) increased the ACh level, decreased the AChE activity, and increased ChAT expression in scopolamine-treated primary cortical neurons. These observations suggest that sulforaphane might exert a significant neuroprotective effect on cholinergic deficit and cognitive impairment. Copyright © 2014. Published by Elsevier Ltd.

  16. Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia.

    Science.gov (United States)

    Umbricht, D; Schmid, L; Koller, R; Vollenweider, F X; Hell, D; Javitt, D C

    2000-12-01

    In patients with schizophrenia, deficient generation of mismatch negativity (MMN)-an event-related potential (ERP) indexing auditory sensory ("echoic") memory-and a selective increase of "context dependent" ("BX") errors in the "A-X" version of the Continuous Performance Test (AX-CPT) indicate an impaired ability to form and use transient memory traces. Animal and human studies implicate deficient N-methyl-D-aspartate receptor (NMDAR) functioning in such abnormalities. In this study, effects of the NMDAR antagonists ketamine on MMN generation and AX-CPT performance were investigated in healthy volunteers to test the hypothesis that NMDARs are critically involved in human MMN generation, and to assess the nature of ketamine-induced deficits in AX-CPT performance. In a single-blind placebo-controlled study, 20 healthy volunteers underwent an infusion with subanesthetic doses of ketamine. The MMN-to-pitch and MMN-to-duration deviants were obtained while subjects performed an AX-CPT. Ketamine significantly decreased the peak amplitudes of the MMN-to-pitch and MMN-to-duration deviants by 27% and 21%, respectively. It induced performance deficits in the AX-CPT characterized by decreased hit rates and specific increases of errors (BX errors), reflecting a failure to form and use transient memory traces of task relevant information. The NMDARs are critically involved in human MMN generation. Deficient MMN in schizophrenia thus suggests deficits in NMDAR-related neurotransmission. N-methyl-D-aspartate receptor dysfunction may also contribute to the impairment of patients with schizophrenia in forming and using transient memory traces in more complex tasks, such as the AX-CPT. Thus, NMDAR-related dysfunction may underlie deficits in transient memory at different levels of information processing in schizophrenia. Arch Gen Psychiatry. 2000;57:1139-1147.

  17. Associative memory and its cerebral correlates in Alzheimer's disease: Evidence for distinct deficits of relational and conjunctive memory

    Science.gov (United States)

    Bastin, Christine; Bahri, Mohamed Ali; Miévis, Frédéric; Lemaire, Christian; Collette, Fabienne; Genon, Sarah; Simon, Jessica; Guillaume, Bénédicte; Diana, Rachel A.; Yonelinas, Andrew P.; Salmon, Eric

    2014-01-01

    This study investigated the impact of Alzheimer's disease (AD) on conjunctive and relational binding in episodic memory. Mild AD patients and controls had to remember item-color associations by imagining color either as a contextual association (relational memory) or as a feature of the item to be encoded (conjunctive memory). Patients' performance in each condition was correlated with cerebral metabolism measured by FDG-PET. The results showed that AD patients had an impaired capacity to remember item-color associations, with deficits in both relational and conjunctive memory. However, performance in the two kinds of associative memory varied independently across patients. Partial least square analyses revealed that poor conjunctive memory was related to hypometabolism in an anterior temporal-posterior fusiform brain network, whereas relational memory correlated with metabolism in regions of the default mode network. These findings support the hypothesis of distinct neural systems specialized in different types of associative memory and point to heterogeneous profiles of memory alteration in Alzheimer's disease as a function of damage to the respective neural networks. PMID:25172390

  18. Associative memory and its cerebral correlates in Alzheimer׳s disease: evidence for distinct deficits of relational and conjunctive memory.

    Science.gov (United States)

    Bastin, Christine; Bahri, Mohamed Ali; Miévis, Frédéric; Lemaire, Christian; Collette, Fabienne; Genon, Sarah; Simon, Jessica; Guillaume, Bénédicte; Diana, Rachel A; Yonelinas, Andrew P; Salmon, Eric

    2014-10-01

    This study investigated the impact of Alzheimer׳s disease (AD) on conjunctive and relational binding in episodic memory. Mild AD patients and controls had to remember item-color associations by imagining color either as a contextual association (relational memory) or as a feature of the item to be encoded (conjunctive memory). Patients׳ performance in each condition was correlated with cerebral metabolism measured by FDG-PET. The results showed that AD patients had an impaired capacity to remember item-color associations, with deficits in both relational and conjunctive memory. However, performance in the two kinds of associative memory varied independently across patients. Partial Least Square analyses revealed that poor conjunctive memory was related to hypometabolism in an anterior temporal-posterior fusiform brain network, whereas relational memory correlated with metabolism in regions of the default mode network. These findings support the hypothesis of distinct neural systems specialized in different types of associative memory and point to heterogeneous profiles of memory alteration in Alzheimer׳s disease as a function of damage to the respective neural networks. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Agrammatism in a case of formal thought disorder: Beyond intellectual decline and working memory deficit.

    LENUS (Irish Health Repository)

    Semkovska, Maria

    2010-02-01

    Previous studies have suggested that naming and syntactic deficits in formal thought disorder may be related to global cognitive decline. This article reports the case of a patient, FM, with formal thought disorder schizophrenia who presents disproportionate deficits in receptive and expressive grammar with respect to his intellectual level of functioning. Syntactic and morphologic components of expressive grammar appeared equally impaired. Deficits in language comprehension were observed independently from working memory limitations. FM showed preserved grammaticality judgment, but defective sentence comprehension where semantic context does not provide heuristics for assigning thematic roles, but syntactic knowledge is essential. These atypical results are discussed within a neurodevelopmental aetiological model of formal thought disorder.

  20. Ginsenoside Rh2 reverses sleep deprivation-induced cognitive deficit in mice.

    Science.gov (United States)

    Lu, Cong; Wang, Yan; Lv, Jingwei; Jiang, Ning; Fan, Bei; Qu, Lina; Li, Yinghui; Chen, Shanguang; Wang, Fengzhong; Liu, Xinmin

    2018-03-12

    Sleep deprivation (SD) negatively caused cognitive deficit, which was associated with oxidative stress induced damage. Ginsenoside Rh2 had the ability to protect against damage caused by reactive oxygen species in vitro, showing antioxidant property. Therefore, it was hypothesized that Ginsenoside Rh2 could prevent SD-induced cognitive deficit via its antioxidant properties. In this study, the effect of Ginsenoside Rh2 on memory impairment induced by sleep deprivation was investigated. The mice were sleep deprived continuously for 14 days using our self-made Sleep Interruption Apparatus (SIA). Ginsenoside Rh2 was administered intraperitoneally at two doses (20 and 40 μmol/kg) for 20 days. Thereafter, behavioral studies were conducted to test the learning and memory ability using object location recognition (OLR) experiment and passive avoidance (PA) test. Additionally, the oxidative stress parameters in the serum and the brain tissues (cortex and hippocampus) were assessed, including the superoxide dismutase (SOD) enzyme activity, the total antioxidant reactivity (TAR), the malondialdehyde (MDA) level, the glutathione (GSH) level, and the lipid peroxidation (LPO) content. The results revealed that SD impaired both spatial and non-spatial memory (P memory impairment induced by SD. Moreover, Ginsenoside Rh2 normalized the reduction of SOD and TAR activities in the serum (P sleep deprivation impaired both spatial and non-spatial memory and Ginsenoside Rh2 reversed this impairment, probably by preventing the oxidative stress damage in the body, including the serum and brain during sleep deprivation. Copyright © 2018. Published by Elsevier B.V.

  1. Experimentally-induced dissociation impairs visual memory.

    Science.gov (United States)

    Brewin, Chris R; Mersaditabari, Niloufar

    2013-12-01

    Dissociation is a phenomenon common in a number of psychological disorders and has been frequently suggested to impair memory for traumatic events. In this study we explored the effects of dissociation on visual memory. A dissociative state was induced experimentally using a mirror-gazing task and its short-term effects on memory performance were investigated. Sixty healthy individuals took part in the experiment. Induced dissociation impaired visual memory performance relative to a control condition; however, the degree of dissociation was not associated with lower memory scores in the experimental group. The results have theoretical and practical implications for individuals who experience frequent dissociative states such as patients with posttraumatic stress disorder (PTSD). Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Association between Early Attention-Deficit/Hyperactivity Symptoms and Current Verbal and Visuo-Spatial Short-Term Memory

    Science.gov (United States)

    Gau, Susan Shur-Fen; Chiang, Huey-Ling

    2013-01-01

    Deficits in short-term memory are common in adolescents with attention-deficit/hyperactivity disorder (ADHD), but their current ADHD symptoms cannot well predict their short-term performance. Taking a developmental perspective, we wanted to clarify the association between ADHD symptoms at early childhood and short-term memory in late childhood and…

  3. Higher body mass index is associated with episodic memory deficits in young adults.

    Science.gov (United States)

    Cheke, Lucy G; Simons, Jon S; Clayton, Nicola S

    2016-11-01

    Obesity has become an international health crisis. There is accumulating evidence that excess bodyweight is associated with changes to the structure and function of the brain and with a number of cognitive deficits. In particular, research suggests that obesity is associated with hippocampal and frontal lobe dysfunction, which would be predicted to impact memory. However, evidence for such memory impairment is currently limited. We hypothesised that higher body mass index (BMI) would be associated with reduced performance on a test of episodic memory that assesses not only content, but also context and feature integration. A total of 50 participants aged 18-35 years, with BMIs ranging from 18 to 51, were tested on a novel what-where-when style episodic memory test: the "Treasure-Hunt Task". This test requires recollection of object, location, and temporal order information within the same paradigm, as well as testing the ability to integrate these features into a single event recollection. Higher BMI was associated with significantly lower performance on the what-where-when (WWW) memory task and all individual elements: object identification, location memory, and temporal order memory. After controlling for age, sex, and years in education, the effect of BMI on the individual what, where, and when tasks remained, while the WWW dropped below significance. This finding of episodic memory deficits in obesity is of concern given the emerging evidence for a role for episodic cognition in appetite regulation.

  4. Auditory Memory deficit in Elderly People with Hearing Loss

    Directory of Open Access Journals (Sweden)

    Zahra Shahidipour

    2013-06-01

    Full Text Available Introduction: Hearing loss is one of the most common problems in elderly people. Functional side effects of hearing loss are various. Due to the fact that hearing loss is the common impairment in elderly people; the importance of its possible effects on auditory memory is undeniable. This study aims to focus on the hearing loss effects on auditory memory.   Materials and Methods: Dichotic Auditory Memory Test (DVMT was performed on 47 elderly people, aged 60 to 80; that were divided in two groups, the first group consisted of elderly people with hearing range of 24 normal and the second one consisted of 23 elderly people with bilateral symmetrical ranged from mild to moderate Sensorineural hearing loss in the high frequency due to aging in both genders.   Results: Significant difference was observed in DVMT between elderly people with normal hearing and those with hearing loss (P

  5. Memory in Early Onset Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder: Similarities and Differences

    Science.gov (United States)

    Udal, Anne H.; Oygarden, Bjorg; Egeland, Jens; Malt, Ulrik F.; Groholt, Berit

    2012-01-01

    Differentiating between early-onset bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) can be difficult. Memory problems are commonly reported in BD, and forgetfulness is among the diagnostic criteria for ADHD. We compared children and adolescents with BD (n = 23), ADHD combined type (ADHD-C; n = 26), BD + ADHD-C (n = 15),…

  6. Congenital Amusia: A Short-Term Memory Deficit for Non-Verbal, but Not Verbal Sounds

    Science.gov (United States)

    Tillmann, Barbara; Schulze, Katrin; Foxton, Jessica M.

    2009-01-01

    Congenital amusia refers to a lifelong disorder of music processing and is linked to pitch-processing deficits. The present study investigated congenital amusics' short-term memory for tones, musical timbres and words. Sequences of five events (tones, timbres or words) were presented in pairs and participants had to indicate whether the sequences…

  7. Memory Deficits Are Associated with Impaired Ability to Modulate Neuronal Excitability in Middle-Aged Mice

    Science.gov (United States)

    Kaczorowski, Catherine C.; Disterhoft, John F.

    2009-01-01

    Normal aging disrupts hippocampal neuroplasticity and learning and memory. Aging deficits were exposed in a subset (30%) of middle-aged mice that performed below criterion on a hippocampal-dependent contextual fear conditioning task. Basal neuronal excitability was comparable in middle-aged and young mice, but learning-related modulation of the…

  8. The Deficit Profile of Working Memory, Inhibition, and Updating in Chinese Children with Reading Difficulties

    Science.gov (United States)

    Peng, Peng; Sha, Tao; Li, Beilei

    2013-01-01

    This study investigated executive function deficits among Chinese children with reading difficulties. Verbal and numerical measures of working memory, inhibition, updating, and processing speed were examined among children with only reading difficulties (RD), children with reading and mathematics difficulties (RDMD), and typically developing peers…

  9. Deficits in episodic memory are related to uncontrolled eating in a sample of healthy adults.

    Science.gov (United States)

    Martin, A A; Davidson, T L; McCrory, M A

    2018-05-01

    Despite a substantial amount of animal data linking deficits in memory inhibition to the development of overeating and obesity, few studies have investigated the relevance of memory inhibition to uncontrolled eating in humans. Further, although memory for recent eating has been implicated as an important contributor to satiety and energy intake, the possibility that variations in episodic memory relate to individual differences in food intake control has been largely neglected. To examine these relationships, we recruited ninety-three adult subjects to attend a single lab session where we assessed body composition, dietary intake, memory performance, and eating behaviors (Three Factor Eating Questionnaire). Episodic recall and memory inhibition were assessed using a well-established measure of memory interference (Retrieval Practice Paradigm). Hierarchical regression analyses indicated that memory inhibition was largely unrelated to participants' eating behaviors; however, episodic recall was reliably predicted by restrained vs. uncontrolled eating: recall was positively associated with strategic dieting (β = 2.45, p = 0.02), avoidance of fatty foods (β = 3.41, p = 0.004), and cognitive restraint (β = 1.55, p = 0.04). In contrast, recall was negatively associated with uncontrolled eating (β = -1.15, p = 0.03) and emotional eating (β = -2.46, p = 0.04). These findings suggest that episodic memory processing is related to uncontrolled eating in humans. The possibility that deficits in episodic memory may contribute to uncontrolled eating by disrupting memory for recent eating is discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Prospective memory in children with attention deficit hyperactivity disorder: a review.

    Science.gov (United States)

    Talbot, Karley-Dale S; Müller, Ulrich; Kerns, Kimberly A

    2017-10-24

    The objective of the paper is to synthesize the research on prospective memory (PM) in children with attention-deficit/hyperactivity disorder (ADHD). Research on PM and ADHD in youth was synthesized according to the PRISMA guidelines and a summary of the types of PM deficits typically seen in these children, as well as the methods currently available to assess and treat these deficits is provided. Suggestions on ways to better manage PM deficits in children's everyday lives are also discussed. Six studies have investigated PM in children with ADHD. The majority of these studies found a deficit in time-based PM, but not event-based PM. The mechanisms underlying this deficit, however, are still unknown. There are currently no specific measures available to clinically assess PM in children and there are no specific evidence-based interventions available that specifically target PM deficits in children with ADHD. Remediation strategies aimed at compensating for these PM deficits in daily life may be most useful. Nevertheless, more research is necessary to better understand PM in children with ADHD.

  11. Angelica keiskei ameliorates scopolamine-induced memory impairments in mice.

    Science.gov (United States)

    Oh, Sa Rang; Kim, Su-Jin; Kim, Dong Hyun; Ryu, Jong Hoon; Ahn, Eun-Mi; Jung, Ji Wook

    2013-01-01

    Memory impairment is the most common symptom in patients with Alzheimer's disease (AD). Angelica keiskei (AK) has traditionally been used as a diuretic, laxative, analeptic and galactagogue. However, the anti-amnesic effects of AK and its molecular mechanisms have yet to be clearly elucidated. The aim of the present study is to evaluate the effects of AK on scopolamine-induced memory impairments in mice. The regulatory effect of AK on memory impairment was investigated using passive avoidance, Y-maze and the Morris water maze tasks. Acetylcholinesterase (AChE) activity assay was performed to investigate the cholinergic antagonistic effect of AK in the hippocampus. The effect of AK on phosphorylation of cAMP response element-binding protein (CREB) and expression of brain-derived neurotrophic factor (BDNF) were evaluated by Western blot assays and immunohistochemistry. The findings showed that AK significantly attenuated scopolamine-induced cognitive impairment in mice. Increase of AChE activity caused by scopolamine was significantly attenuated by AK. Additionally, AK significantly recovered the phosphorylation of CREB and expression of BDNF reduced by scopolamine in the hippocampus. Taken together, these results provide experimental evidence that AK might be a useful agent in preventing deficit of learning and memory caused by AD and aging.

  12. Possible mechanism involved in sleep deprivation-induced memory dysfunction.

    Science.gov (United States)

    Kalonia, H; Bishnoi, M; Kumar, A

    2008-09-01

    Sleep deprivation disrupts various vital biological and metabolic processes that are necessary for health. The present study was designed to investigate the possible mechanisms of sleep deprivation-induced memory dysfunction by using different behavioral, biochemical and neurochemical parameters. Male Wistar rats were sleep deprived for 72 h using a grid suspended over water. Elevated plus maze, passive avoidance and Morris water maze tests were used to assess memory retention in 72-h sleep-deprived animals. Various electrophysiological (sleep-wake cycle), biochemical (lipid peroxidation, reduced glutathione, nitrite, catalase, acetylcholinesterase) and neurochemical parameters (norepinephrine, dopamine and serotonin) were also assessed. Sleep deprivation resulted in memory dysfunction in all the behavioral paradigms, alteration in the sleep-wake cycle (delayed sleep latency, shortening of rapid eye movement [REM] and non-REM [NREM] sleep and increased waking period) and oxidative stress (increased lipid peroxidation and nitrite levels, depletion of reduced glutathione and catalase activity). In addition, increased levels of acetylcholinesterase (AChE; the enzyme responsible for the degradation of acetylcholine) and reduction in norepinephrine and dopamine levels were seen in 72-h sleep-deprived animals. In conclusion, sleep deprivation-induced memory deficits may possibly be due to the combined effect of oxidative damage and alterations in neurotransmitter levels. Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

  13. Spatial Working Memory Deficits in Male Rats Following Neonatal Hypoxic Ischemic Brain Injury Can Be Attenuated by Task Modifications

    Directory of Open Access Journals (Sweden)

    Amanda L. Smith

    2014-04-01

    Full Text Available Hypoxia-ischemia (HI; reduction in blood/oxygen supply is common in infants with serious birth complications, such as prolonged labor and cord prolapse, as well as in infants born prematurely (<37 weeks gestational age; GA. Most often, HI can lead to brain injury in the form of cortical and subcortical damage, as well as later cognitive/behavioral deficits. A common domain of impairment is working memory, which can be associated with heightened incidence of developmental disorders. To further characterize these clinical issues, the current investigation describes data from a rodent model of HI induced on postnatal (P7, an age comparable to a term (GA 36–38 human. Specifically, we sought to assess working memory using an eight-arm radial water maze paradigm. Study 1 used a modified version of the paradigm, which requires a step-wise change in spatial memory via progressively more difficult tasks, as well as multiple daily trials for extra learning opportunity. Results were surprising and revealed a small HI deficit only for the final and most difficult condition, when a delay before test trial was introduced. Study 2 again used the modified radial arm maze, but presented the most difficult condition from the start, and only one daily test trial. Here, results were expected and revealed a robust and consistent HI deficit across all weeks. Combined results indicate that male HI rats can learn a difficult spatial working memory task if it is presented in a graded multi-trial format, but performance is poor and does not appear to remediate if the task is presented with high initial memory demand. Male HI rats in both studies displayed impulsive characteristics throughout testing evidenced as reduced choice latencies despite more errors. This aspect of behavioral results is consistent with impulsiveness as a core symptom of ADHD—a diagnosis common in children with HI insult. Overall findings suggest that task specific behavioral modifications are

  14. Memory deficits following neonatal critical illness: A common neurodevelopmental pathway

    NARCIS (Netherlands)

    R.M. Schiller (Raisa); H. IJsselstijn (Hanneke); A. Hoskote (Aparna); T.J.H. White (Tonya); F.C. Verhulst (Frank); A.F.J. van Heijst (Arno); D. Tibboel (Dick)

    2017-01-01

    textabstractSummary Over the last decade, knowledge has emerged that children growing up after neonatal critical illness, irrespective of underlying diagnosis, are at risk of memory impairment and school problems. Strikingly, these problems are manifest even when intelligence is normal. In this

  15. Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats.

    Science.gov (United States)

    Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Ben, Juliana; Guaita, Gisele O; Pita, Inês R; Sequeira, Ana C; Pereira, Frederico C; Walz, Roger; Takahashi, Reinaldo N; Bertoglio, Leandro J; Da Cunha, Cláudio; Cunha, Rodrigo A; Prediger, Rui D

    2016-03-15

    Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20μg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10μg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10μg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Reversing roles: a cognitive strategy for undoing memory deficits associated with token status.

    Science.gov (United States)

    Saenz, D S; Lord, C G

    1989-05-01

    Tested whether having tokens (Ts) adopt the role of judge reduces cognitive deficits; examined several hypotheses to explain these deficits. In 3 experiments, Ss were asked to remember as many as possible of opinions exchanged in a group interaction with 3 actors. Experiment 1 demonstrated that judging majority members helped gender Ts improve their memory and ruled out self-denigration as a mediator of token deficits. Experiment 2 indicated that judging others was effective regardless of whether the others were said to know about it or not, ruling out insulation from evaluative scrutiny as a viable mediator for the judge role. Experiment 3 suggested the judge role restores completely the Ts, cognitive capacities and ruled out heightened responsibility as an explanation for the improved memory of judges. This work suggests that Ts may perform better if they can restructure cognitively their social environments.

  17. Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents.

    Science.gov (United States)

    Gui, Wen-Shan; Wei, Xiao; Mai, Chun-Lin; Murugan, Madhuvika; Wu, Long-Jun; Xin, Wen-Jun; Zhou, Li-Jun; Liu, Xian-Guo

    2016-01-01

    Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice. Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β. Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression. © The Author(s) 2016.

  18. Verbal declarative memory impairments in specific language impairment are related to working memory deficits

    OpenAIRE

    Lum, Jarrad A.G.; Ullman, Michael T.; Conti-Ramsden, Gina

    2015-01-01

    This study examined verbal declarative memory functioning in SLI and its relationship to working memory. Encoding, recall, and recognition of verbal information was examined in children with SLI who had below average working memory (SLILow WM), children with SLI who had average working memory (SLIAvg. WM) and, a group of non-language impaired children with average working memory (TDAvg. WM). The SLILow WM group was significantly worse than both the SLIAvg. WM and TDAvg. WM groups at encoding ...

  19. Neurogenic Stuttering and Lateralized Motor Deficits Induced by Tranylcypromine

    Directory of Open Access Journals (Sweden)

    J. D. Duffy

    1994-01-01

    Full Text Available A case of neurogenic stuttering induced by the monoamine oxidase inhibitor tranylcypromine is described. The association of neurogenic stuttering with acquired lateralized motor deficits in the patient described is discussed with reference to current theories regarding the pathogenesis of neurogenic stuttering.

  20. Neuropeptide S mitigates spatial memory impairment induced by rapid eye movement sleep deprivation in rats.

    Science.gov (United States)

    Zhao, Zhengqing; Huang, Liuqing; Wu, Huijuan; Li, Yanpeng; Zhang, Lin; Yin, You; Xiang, Zhenghua; Zhao, Zhongxin

    2010-06-23

    Rapid eye movement (REM) sleep deprivation causes learning and memory deficits. Neuropeptide S, a newly discovered neuropeptide, has been shown to regulate arousal, anxiety, and may enhance long-term memory formation and spatial memory. However, it is unknown whether neuropeptide S could improve the REM sleep deprivation-induced memory impairment. Here, we report that 72-h REM sleep deprivation in rats resulted in spatial memory impairment and reduced phosphorylation level of cAMP-response element binding protein in the hippocampus, both of which were reversed by central administration of neuropeptide S. The results suggest that neuropeptide S mitigates spatial memory impairment in rats induced by 72-h REM sleep deprivation, possibly through activating cAMP-response element binding protein phosphorylation in the hippocampus.

  1. False memories for dissonance inducing events.

    Science.gov (United States)

    Rodriguez, Dario N; Strange, Deryn

    2015-01-01

    Memories serve as a "database" of the self and people often produce distorted memories that support their self-concepts. One, surprisingly untested, possibility is that cognitive dissonance may be one mechanism by which people may misremember their past. We tested this hypothesis using an induced-compliance paradigm: participants either chose or were forced to write a counterattitudinal essay supporting a tuition increase and were afforded the opportunity to reduce dissonance via attitude shift or denial of responsibility. They then reported their memories for the experimental instructions and their initial attitudes (assessed two days prior to the laboratory session). Participants who chose to write the essay exhibited the predicted attitude-shift effect, and were more likely to misremember their initial attitudes and the experimental instruction than those who were forced to write the essay. Overall, our results provide evidence that cognitive dissonance may yield memory distortion, filling a significant gap in the motivated cognition and memory literatures.

  2. Neuroprotective mechanism of Lycium barbarum polysaccharides against hippocampal-dependent spatial memory deficits in a rat model of obstructive sleep apnea.

    Science.gov (United States)

    Lam, Chun-Sing; Tipoe, George Lim; So, Kwok-Fai; Fung, Man-Lung

    2015-01-01

    Chronic intermittent hypoxia (CIH) is a hallmark of obstructive sleep apnea (OSA), which induces hippocampal injuries mediated by oxidative stress. This study aims to examine the neuroprotective mechanism of Lycium barbarum polysaccharides (LBP) against CIH-induced spatial memory deficits. Adult Sprague-Dawley rats were exposed to hypoxic treatment resembling a severe OSA condition for a week. The animals were orally fed with LBP solution (1 mg/kg) daily 2 hours prior to hypoxia or in air for the control. The effect of LBP on the spatial memory and levels of oxidative stress, inflammation, endoplasmic reticulum (ER) stress, apoptosis and neurogenesis in the hippocampus was examined. There was a significant deficit in the spatial memory and an elevated level of malondialdehyde with a decreased expression of antioxidant enzymes (SOD, GPx-1) in the hypoxic group when compared with the normoxic control. In addition, redox-sensitive nuclear factor kappa B (NFКB) canonical pathway was activated with a translocation of NFКB members (p65, p50) and increased expression levels of NFКB-dependent inflammatory cytokines and mediator (TNFα, IL-1β, COX-2); also, a significantly elevated level of ER stress (GRP78/Bip, PERK, CHOP) and autophagic flux in the hypoxic group, leading to neuronal apoptosis in hippocampal subfields (DG, CA1, CA3). Remarkably, LBP administration normalized the elevated level of oxidative stress, neuroinflammation, ER stress, autophagic flux and apoptosis induced by hypoxia. Moreover, LBP significantly mitigated both the caspase-dependent intrinsic (Bax, Bcl2, cytochrome C, cleaved caspase-3) and extrinsic (FADD, cleaved caspase-8, Bid) signaling apoptotic cascades. Furthermore, LBP administration prevented the spatial memory deficit and enhanced the hippocampal neurogenesis induced by hypoxia. Our results suggest that LBP is neuroprotective against CIH-induced hippocampal-dependent spatial memory deficits by promoting hippocampal neurogenesis and

  3. Neuroprotective mechanism of Lycium barbarum polysaccharides against hippocampal-dependent spatial memory deficits in a rat model of obstructive sleep apnea.

    Directory of Open Access Journals (Sweden)

    Chun-Sing Lam

    Full Text Available Chronic intermittent hypoxia (CIH is a hallmark of obstructive sleep apnea (OSA, which induces hippocampal injuries mediated by oxidative stress. This study aims to examine the neuroprotective mechanism of Lycium barbarum polysaccharides (LBP against CIH-induced spatial memory deficits. Adult Sprague-Dawley rats were exposed to hypoxic treatment resembling a severe OSA condition for a week. The animals were orally fed with LBP solution (1 mg/kg daily 2 hours prior to hypoxia or in air for the control. The effect of LBP on the spatial memory and levels of oxidative stress, inflammation, endoplasmic reticulum (ER stress, apoptosis and neurogenesis in the hippocampus was examined. There was a significant deficit in the spatial memory and an elevated level of malondialdehyde with a decreased expression of antioxidant enzymes (SOD, GPx-1 in the hypoxic group when compared with the normoxic control. In addition, redox-sensitive nuclear factor kappa B (NFКB canonical pathway was activated with a translocation of NFКB members (p65, p50 and increased expression levels of NFКB-dependent inflammatory cytokines and mediator (TNFα, IL-1β, COX-2; also, a significantly elevated level of ER stress (GRP78/Bip, PERK, CHOP and autophagic flux in the hypoxic group, leading to neuronal apoptosis in hippocampal subfields (DG, CA1, CA3. Remarkably, LBP administration normalized the elevated level of oxidative stress, neuroinflammation, ER stress, autophagic flux and apoptosis induced by hypoxia. Moreover, LBP significantly mitigated both the caspase-dependent intrinsic (Bax, Bcl2, cytochrome C, cleaved caspase-3 and extrinsic (FADD, cleaved caspase-8, Bid signaling apoptotic cascades. Furthermore, LBP administration prevented the spatial memory deficit and enhanced the hippocampal neurogenesis induced by hypoxia. Our results suggest that LBP is neuroprotective against CIH-induced hippocampal-dependent spatial memory deficits by promoting hippocampal neurogenesis

  4. Thrombin-induced microglial activation impairs hippocampal neurogenesis and spatial memory ability in mice.

    Science.gov (United States)

    Yang, Yuan; Zhang, Meikui; Kang, Xiaoni; Jiang, Chen; Zhang, Huan; Wang, Pei; Li, Jingjing

    2015-09-26

    To investigate the effects of microglia/macrophages activation induced by intrastriatal thrombin injection on dentate gyrus neurogenesis and spatial memory ability in mice. The male C57BL/6 mice were divided into 4 groups of 10: sham, intracerebral hemorrhage (ICH), ICH + hirudin (thrombin inhibitor), and ICH + indometacin (Indo, an anti-inflammation drug). ICH model was created by intrastriatal thrombin (1U) injection. BrdU (50 mg/kg) was administrated on the same day after surgery for 6 consecutive days. Motor functions were evaluated with rotarod and beam walking tests. The spatial memory deficit was measured with Morris water maze (MWM). Cell quantification was performed for doublecortin (DCX, immature neuron), BrdU (S-phase proliferating cell population) and CD68 (activated microglia/macrophage) immune-reactive cells. Microglia/macrophages activation induced by intrastriatal thrombin injection reduced hippocampal neurogenesis and impaired spatial memory ability, but did not affect the motor function at 3 and 5 days post-injury. Both hirudin and indometacin reduced microglia/macrophages activation, enhanced hippocampal neurogenesis, and improved spatial memory ability in mice. Microglia/macrophages activation induced by intrastriatal thrombin injection might be responsible for the spatial memory deficit. Targeting both thrombin and inflammation systems in acute phase of ICH might be important in alleviating the significant spatial memory deficits.

  5. Blonanserin Ameliorates Phencyclidine-Induced Visual-Recognition Memory Deficits: the Complex Mechanism of Blonanserin Action Involving D3-5-HT2A and D1-NMDA Receptors in the mPFC

    Science.gov (United States)

    Hida, Hirotake; Mouri, Akihiro; Mori, Kentaro; Matsumoto, Yurie; Seki, Takeshi; Taniguchi, Masayuki; Yamada, Kiyofumi; Iwamoto, Kunihiro; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

    2015-01-01

    Blonanserin differs from currently used serotonin 5-HT2A/dopamine-D2 receptor antagonists in that it exhibits higher affinity for dopamine-D2/3 receptors than for serotonin 5-HT2A receptors. We investigated the involvement of dopamine-D3 receptors in the effects of blonanserin on cognitive impairment in an animal model of schizophrenia. We also sought to elucidate the molecular mechanism underlying this involvement. Blonanserin, as well as olanzapine, significantly ameliorated phencyclidine (PCP)-induced impairment of visual-recognition memory, as demonstrated by the novel-object recognition test (NORT) and increased extracellular dopamine levels in the medial prefrontal cortex (mPFC). With blonanserin, both of these effects were antagonized by DOI (a serotonin 5-HT2A receptor agonist) and 7-OH-DPAT (a dopamine-D3 receptor agonist), whereas the effects of olanzapine were antagonized by DOI but not by 7-OH-DPAT. The ameliorating effect was also antagonized by SCH23390 (a dopamine-D1 receptor antagonist) and H-89 (a protein kinase A (PKA) inhibitor). Blonanserin significantly remediated the decrease in phosphorylation levels of PKA at Thr197 and of NR1 (an essential subunit of N-methyl-D-aspartate (NMDA) receptors) at Ser897 by PKA in the mPFC after a NORT training session in the PCP-administered mice. There were no differences in the levels of NR1 phosphorylated at Ser896 by PKC in any group. These results suggest that the ameliorating effect of blonanserin on PCP-induced cognitive impairment is associated with indirect functional stimulation of the dopamine-D1-PKA-NMDA receptor pathway following augmentation of dopaminergic neurotransmission due to inhibition of both dopamine-D3 and serotonin 5-HT2A receptors in the mPFC. PMID:25120077

  6. Blonanserin ameliorates phencyclidine-induced visual-recognition memory deficits: the complex mechanism of blonanserin action involving D₃-5-HT₂A and D₁-NMDA receptors in the mPFC.

    Science.gov (United States)

    Hida, Hirotake; Mouri, Akihiro; Mori, Kentaro; Matsumoto, Yurie; Seki, Takeshi; Taniguchi, Masayuki; Yamada, Kiyofumi; Iwamoto, Kunihiro; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

    2015-02-01

    Blonanserin differs from currently used serotonin 5-HT₂A/dopamine-D₂ receptor antagonists in that it exhibits higher affinity for dopamine-D₂/₃ receptors than for serotonin 5-HT₂A receptors. We investigated the involvement of dopamine-D₃ receptors in the effects of blonanserin on cognitive impairment in an animal model of schizophrenia. We also sought to elucidate the molecular mechanism underlying this involvement. Blonanserin, as well as olanzapine, significantly ameliorated phencyclidine (PCP)-induced impairment of visual-recognition memory, as demonstrated by the novel-object recognition test (NORT) and increased extracellular dopamine levels in the medial prefrontal cortex (mPFC). With blonanserin, both of these effects were antagonized by DOI (a serotonin 5-HT₂A receptor agonist) and 7-OH-DPAT (a dopamine-D₃ receptor agonist), whereas the effects of olanzapine were antagonized by DOI but not by 7-OH-DPAT. The ameliorating effect was also antagonized by SCH23390 (a dopamine-D₁ receptor antagonist) and H-89 (a protein kinase A (PKA) inhibitor). Blonanserin significantly remediated the decrease in phosphorylation levels of PKA at Thr(197) and of NR1 (an essential subunit of N-methyl-D-aspartate (NMDA) receptors) at Ser(897) by PKA in the mPFC after a NORT training session in the PCP-administered mice. There were no differences in the levels of NR1 phosphorylated at Ser(896) by PKC in any group. These results suggest that the ameliorating effect of blonanserin on PCP-induced cognitive impairment is associated with indirect functional stimulation of the dopamine-D₁-PKA-NMDA receptor pathway following augmentation of dopaminergic neurotransmission due to inhibition of both dopamine-D₃ and serotonin 5-HT₂A receptors in the mPFC.

  7. Ellagic acid ameliorates learning and memory deficits in a rat model of Alzheimer's disease: an exploration of underlying mechanisms.

    Science.gov (United States)

    Kiasalari, Zahra; Heydarifard, Rana; Khalili, Mohsen; Afshin-Majd, Siamak; Baluchnejadmojarad, Tourandokht; Zahedi, Elham; Sanaierad, Ashkan; Roghani, Mehrdad

    2017-06-01

    Alzheimer's disease (AD) is a neurodegenerative disorder with irreversible loss of intellectual abilities. Current therapies for AD are still insufficient. In this study, the effect of ellagic acid on learning and memory deficits was evaluated in intrahippocampal amyloid beta (Aβ 25-35 )-microinjected rats and its modes of action were also explored. AD rat model was induced by bilateral intrahippocampal microinjection of Aβ 25-35 and ellagic acid was daily administered (10, 50, and 100 mg/kg), and learning, recognition memory, and spatial memory were evaluated in addition to histochemical assessment, oxidative stress, cholinesterases activity, and level of nuclear factor-kappaB (NF-κB), Toll-like receptor 4 (TLR4), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). The amyloid beta-microinjected rats showed a lower discrimination ratio in novel object and alternation score in Y maze tasks and exhibited an impairment of retention and recall capability in passive avoidance paradigm and higher working and reference memory errors in radial arm maze (RAM). In addition, amyloid beta group showed a lower number of Nissl-stained neurons in CA1 area in addition to enhanced oxidative stress, higher activity of cholinesterases, greater level of NF-κB and TLR4, and lower level of nuclear/cytoplasmic ratio for Nrf2 and ellagic acid at a dose of 100 mg/kg significantly prevented most of these abnormal alterations. Ellagic acid pretreatment of intrahippocampal amyloid beta-microinjected rats could dose-dependently improve learning and memory deficits via neuronal protection and at molecular level through mitigation of oxidative stress and acetylcholinesterase (AChE) activity and modulation of NF-κB/Nrf2/TLR4 signaling pathway.

  8. Age-related declines in visuospatial working memory correlate with deficits in explicit motor sequence learning.

    Science.gov (United States)

    Bo, J; Borza, V; Seidler, R D

    2009-11-01

    Numerous studies have shown that older adults exhibit deficits in motor sequence learning, but the mechanisms underlying this effect remain unclear. Our recent work has shown that visuospatial working-memory capacity predicts the rate of motor sequence learning and the length of motor chunks formed during explicit sequence learning in young adults. In the current study, we evaluate whether age-related deficits in working memory explain the reduced rate of motor sequence learning in older adults. We found that older adults exhibited a correlation between visuospatial working-memory capacity and motor sequence chunk length, as we observed previously in young adults. In addition, older adults exhibited an overall reduction in both working-memory capacity and motor chunk length compared with that of young adults. However, individual variations in visuospatial working-memory capacity did not correlate with the rate of learning in older adults. These results indicate that working memory declines with age at least partially explain age-related differences in explicit motor sequence learning.

  9. Visual short-term memory binding deficit in familial Alzheimer's disease.

    Science.gov (United States)

    Liang, Yuying; Pertzov, Yoni; Nicholas, Jennifer M; Henley, Susie M D; Crutch, Sebastian; Woodward, Felix; Leung, Kelvin; Fox, Nick C; Husain, Masud

    2016-05-01

    Long-term episodic memory deficits in Alzheimer's disease (AD) are well characterised but, until recently, short-term memory (STM) function has attracted far less attention. We employed a recently-developed, delayed reproduction task which requires participants to reproduce precisely the remembered location of items they had seen only seconds previously. This paradigm provides not only a continuous measure of localization error in memory, but also an index of relational binding by determining the frequency with which an object is misplaced to the location of one of the other items held in memory. Such binding errors in STM have previously been found on this task to be sensitive to medial temporal lobe (MTL) damage in focal lesion cases. Twenty individuals with pathological mutations in presenilin 1 or amyloid precursor protein genes for familial Alzheimer's disease (FAD) were tested together with 62 healthy controls. Participants were assessed using the delayed reproduction memory task, a standard neuropsychological battery and structural MRI. Overall, FAD mutation carriers were worse than controls for object identity as well as in gross localization memory performance. Moreover, they showed greater misbinding of object identity and location than healthy controls. Thus they would often mislocalize a correctly-identified item to the location of one of the other items held in memory. Significantly, asymptomatic gene carriers - who performed similarly to healthy controls on standard neuropsychological tests - had a specific impairment in object-location binding, despite intact memory for object identity and location. Consistent with the hypothesis that the hippocampus is critically involved in relational binding regardless of memory duration, decreased hippocampal volume across FAD participants was significantly associated with deficits in object-location binding but not with recall precision for object identity or localization. Object-location binding may therefore

  10. [Memory characteristic in boys with attention deficit/hyperactivity disorder comorbid learning disability].

    Science.gov (United States)

    Wu, Zhaomin; Wang, Na; Qian, Qiujin; Yang, Li; Qian, Ying; Liu, Lu; Liu, Yuxin; Cheng, Jia; Sun, Li; Cao, Qingjiu; Wang, Yufeng

    2014-06-10

    To explore the memory characteristic in boys with attention-deficit/hyperactivity disorder (ADHD) plus learning disability (LD). A total of 97 ADHD boys with comorbid LD (ADHD+LD), 97 ADHD boys without comorbid LD (ADHD-LD) and 97 healthy controls (based on the criteria of DSM-IV) were recruited from the outpatient clinic of Peking University Sixth Hospital from December 2003 to September 2012. Individuals across three groups were matched by ages, intelligence quotient (IQ) and ADHD subtypes. The Wechsler Memory Scale (WMS) was used to access the characteristics of several memory domains. ADHD +LD group performed the worst and control group the best in memory quotient (MQ) (90 ± 15 vs 98 ± 14 & 104 ± 14) and long-term memory domain ((36.0 ± 10.2) vs (42.1 ± 7.8) & (45.6 ± 6.7) score, all P 0.05). In most subscales of WMS, ADHD+LD group scored significantly lower than both ADHD-LD and control group in current information and orientation, mental control (1→100) , mental control (100→1) and associate learning subscales ( (8.8 ± 3.1) vs (10.0 ± 3.0) & (9.9 ± 2.3) score, (8.7 ± 4.1) vs (10.0 ± 3.9) & (11.1 ± 3.6) score, (10.7 ± 3.9) vs (12.9 ± 2.8) & (13.7 ± 2.2) score, (9.8 ± 3.1) vs (10.8 ± 2.6) & (11.1 ± 2.1) score, all P 0.05). Boys with ADHD comorbid LD show deficits in overall memory function and long-term memory while short-term memory is partially damaged. Impairment in immediate memory is not detected.

  11. Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Yazir, Yusufhan; Utkan, Tijen; Gacar, Nejat; Aricioglu, Feyza

    2015-01-01

    A number of studies have recently focused on the neuroprotective and anti-inflammatory effects of resveratrol. In prior studies, we described its beneficial effects on scopolamine-induced learning deficits in rats. The aim of this study was to investigate the effects of resveratrol on emotional and spatial cognitive functions, neurotropic factor expression, and plasma levels of proinflammatory cytokines in rats exposed to chronic unpredictable mild stress (CUMS), which is known to induce cognitive deficits. Resveratrol (5 or 20mg/kg) was administered intraperitoneally for 35 days. Rats in the CUMS group and in the 5mg/kg resveratrol+CUMS group performed poorly in tasks designed to assess emotional and spatial learning and memory. The 20mg/kg resveratrol+CUMS group showed improved performance compared to the CUMS group. In addition, the CUMS procedure induced lower expression of brain-derived neurotrophic factor and c-Fos in hippocampal CA1 and CA3 and in the amygdala of stressed rats. These effects were reversed by chronic administration of resveratrol (20mg/kg). In addition, plasma levels of tumor necrosis factor-alpha and interleukin-1 beta were increased by CUMS, but were restored to normal by resveratrol. These results indicate that resveratrol significantly attenuates the deficits in emotional learning and spatial memory seen in chronically stressed rats. These effects may be related to resveratrol-mediated changes in neurotrophin factor expression in hippocampus and in levels of proinflammatory cytokines in circulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. No deficits in nonverbal memory, metamemory and internal as well as external source memory in obsessive-compulsive disorder (OCD).

    Science.gov (United States)

    Moritz, Steffen; Ruhe, Claudia; Jelinek, Lena; Naber, Dieter

    2009-04-01

    A large body of literature suggests that some symptoms of obsessive-compulsive disorder (OCD) result from mnemonic dysfunctions. The present study tested various formulations of the memory deficit hypothesis considering important moderators, such as depression and response slowing. Thirty-two OCD patients and 32 healthy controls were presented verbal or nonverbal instructions for actions (e.g. simple gestures). These actions should either be performed or imagined. For recognition, previously presented as well as novel actions were displayed. Decisions had to be made whether an action was previously displayed (verbally vs. nonverbally) or not and whether an action was performed or imagined (internal source memory). Moreover, both judgments required confidence ratings. Groups did not differ in memory accuracy and metamemory for verbally presented material. Patients displayed some impairment for nonverbally presented material and imagined instructions, which, however, could be fully accounted for by response slowing and depressive symptoms. The study challenges the view that primary memory deficits underlie OCD or any of its subtypes. We claim that research should move forward from the mere study of objective impairment to the assessment of cognitive performance in conjunction with personality traits such as inflated responsibility.

  13. Memory deficits with intact cognitive control in the methylazoxymethanol acetate (MAM) exposure model of neurodevelopmental insult.

    Science.gov (United States)

    O'Reilly, Kally C; Perica, Maria I; Fenton, André A

    2016-10-01

    Cognitive impairments are amongst the most debilitating deficits of schizophrenia and the best predictor of functional outcome. Schizophrenia is hypothesized to have a neurodevelopmental origin, making animal models of neurodevelopmental insult important for testing predictions that early insults will impair cognitive function. Rats exposed to methylazoxymethanol acetate (MAM) at gestational day 17 display morphological, physiological and behavioral abnormalities relevant to schizophrenia. Here we investigate the cognitive abilities of adult MAM rats. We examined brain activity in MAM rats by histochemically assessing cytochrome oxidase enzyme activity, a metabolic marker of neuronal activity. To assess cognition, we used a hippocampus-dependent two-frame active place avoidance paradigm to examine learning and spatial memory, as well as cognitive control and flexibility using the same environment and evaluating the same set of behaviors. We confirmed that adult MAM rats have altered hippocampal morphology and brain function, and that they are hyperactive in an open field. The latter likely indicates MAM rats have a sensorimotor gating deficit that is common to many animal models used for schizophrenia research. On first inspection, cognitive control seems impaired in MAM rats, indicated by more errors during the two-frame active place avoidance task. Because MAM rats are hyperactive throughout place avoidance training, we considered the possibility that the hyperlocomotion may account for the apparent cognitive deficits. These deficits were reduced on the basis of measures of cognitive performance that account for motor activity differences. However, though other aspects of memory are intact, the ability of MAM rats to express trial-to-trial memory is delayed compared to control rats. These findings suggest that spatial learning and cognitive abilities are largely intact, that the most prominent cognitive deficit is specific to acquiring memory in the MAM

  14. Theory of Mind Deficit versus Faulty Procedural Memory in Autism Spectrum Disorders

    Science.gov (United States)

    Romero-Munguía, Miguel Ángel

    2013-01-01

    Individuals with autism spectrum disorders (ASD) have impairments in social interaction, communicative capacity, and behavioral flexibility (core triad). Three major cognitive theories (theory of mind deficit, weak central coherence, and executive dysfunction) seem to explain many of these impairments. Currently, however, the empathizing-systemizing (a newer version of the theory of mind deficit account) and mnesic imbalance theories are the only ones that attempt to explain all these core triadic symptoms of ASD On the other hand, theory of mind deficit in empathizing-systemizing theory is the most influential account for ASD, but its counterpart in the mnesic imbalance theory, faulty procedural memory, seems to occur earlier in development; consequently, this might be a better solution to the problem of the etiology of ASD, if it truly meets the precedence criterion. Hence, in the present paper I review the reasoning in favor of the theory of mind deficit but with a new interpretation based on the mnesic imbalance theory, which posits that faulty procedural memory causes deficits in several cognitive skills, resulting in poor performance in theory of mind tasks. PMID:23862063

  15. Theory of Mind Deficit versus Faulty Procedural Memory in Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Romero-Munguía

    2013-01-01

    Full Text Available Individuals with autism spectrum disorders (ASD have impairments in social interaction, communicative capacity, and behavioral flexibility (core triad. Three major cognitive theories (theory of mind deficit, weak central coherence, and executive dysfunction seem to explain many of these impairments. Currently, however, the empathizing-systemizing (a newer version of the theory of mind deficit account and mnesic imbalance theories are the only ones that attempt to explain all these core triadic symptoms of ASD On the other hand, theory of mind deficit in empathizing-systemizing theory is the most influential account for ASD, but its counterpart in the mnesic imbalance theory, faulty procedural memory, seems to occur earlier in development; consequently, this might be a better solution to the problem of the etiology of ASD, if it truly meets the precedence criterion. Hence, in the present paper I review the reasoning in favor of the theory of mind deficit but with a new interpretation based on the mnesic imbalance theory, which posits that faulty procedural memory causes deficits in several cognitive skills, resulting in poor performance in theory of mind tasks.

  16. Protective effect of ascorbic acid and Ginkgo biloba against learning and memory deficits caused by fluoride.

    Science.gov (United States)

    Jetti, Raghu; Raghuveer, C V; Mallikarjuna, Rao C

    2016-01-01

    Fluoride is present in the ground water, World Health Organization permitted level of fluoride in the ground water is 0.5 ppm. Tooth pastes, mouth washes, tea and sea fish are the sources of fluoride. Exposure to these multiple sources results in several adverse effects in addition to the fluorosis. The present study aimed to test the effect of vitamin C and Ginkgo biloba against the behavioural deficits caused by fluoride. Rats were divided into five groups with six animals in each group (n = 6). Control group received ordinary tap water with 0.5 ppm of fluoride, the remaining groups received 100 ppm of fluoride for 30 days prior to fluoride exposure. Two groups of animals received 100 mg/kg body weight of vitamin C and G. biloba for 15 days prior to fluoride exposure. After 45 days, behavioural studies (T-Maze, passive avoidance) were conducted on the experimental animals. The results of the present study showed no behavioural deficits in the control group of animals however, the rats that received fluoride water exhibited impairment in their spatial learning and memory deficits. The deficits are not marked in the vitamin C and G. biloba groups. To conclude chronic exposure to high levels of fluoride causes severe impairment in the spatial learning and memory, these deficits can be ameliorated with the vitamin C and G. biloba. © The Author(s) 2013.

  17. Environmental enrichment restores cognitive deficits induced by experimental childhood meningitis.

    Science.gov (United States)

    Barichello, Tatiana; Fagundes, Glauco D; Generoso, Jaqueline S; Dagostin, Caroline S; Simões, Lutiana R; Vilela, Márcia C; Comim, Clarissa M; Petronilho, Fabricia; Quevedo, João; Teixeira, Antonio L

    2014-01-01

    To evaluate the influence of environmental enrichment (EE) on memory, cytokines, and brain-derived neurotrophic factor (BDNF) in the brain of adult rats subjected to experimental pneumococcal meningitis during infancy. On postnatal day 11, the animals received either artificial cerebrospinal fluid (CSF) or Streptococcus pneumoniae suspension intracisternally at 1 × 10(6) CFU/mL and remained with their mothers until age 21 days. Animals were divided into the following groups: control, control + EE, meningitis, and meningitis + EE. EE began at 21 days and continued until 60 days of age (adulthood). EE consisted of a large cage with three floors, ramps, running wheels, and objects of different shapes and textures. At 60 days, animals were randomized and subjected to habituation to the open-field task and the step-down inhibitory avoidance task. After the tasks, the hippocampus and CSF were isolated for analysis. The meningitis group showed no difference in performance between training and test sessions of the open-field task, suggesting habituation memory impairment; in the meningitis + EE group, performance was significantly different, showing preservation of habituation memory. In the step-down inhibitory avoidance task, there were no differences in behavior between training and test sessions in the meningitis group, showing aversive memory impairment; conversely, differences were observed in the meningitis + EE group, demonstrating aversive memory preservation. In the two meningitis groups, IL-4, IL-10, and BDNF levels were increased in the hippocampus, and BDNF levels in the CSF. The data presented suggest that EE, a non-invasive therapy, enables recovery from memory deficits caused by neonatal meningitis.

  18. Humanin attenuates Alzheimer-like cognitive deficits and pathological changes induced by amyloid β-peptide in rats.

    Science.gov (United States)

    Chai, Gao-Shang; Duan, Dong-Xiao; Ma, Rong-Hong; Shen, Jian-Ying; Li, Hong-Lian; Ma, Zhi-Wei; Luo, Yu; Wang, Lu; Qi, Xin-Hua; Wang, Qun; Wang, Jian-Zhi; Wei, Zelan; Mousseau, Darrell D; Wang, Li; Liu, Gongping

    2014-12-01

    Amyloid β-peptide (Aβ) has been implicated as a key molecule in the neurodegenerative cascades of Alzheimer's disease (AD). Humanin (HN) is a secretory peptide that inhibits the neurotoxicity of Aβ. However, the mechanism(s) by which HN exerts its neuroprotection against Aβ-induced AD-like pathological changes and memory deficits are yet to be completely defined. In the present study, we provided evidence that treatment of rats with HN increases the number of dendritic branches and the density of dendritic spines, and upregulates pre- and post-synaptic protein levels; these effects lead to enhanced long-term potentiation and amelioration of the memory deficits induced by Aβ(1-42). HN also attenuated Aβ(1-42)-induced tau hyperphosphorylation, apparently by inhibiting the phosphorylation of Tyr307 on the inhibitory protein phosphatase-2A (PP2A) catalytic subunit and thereby activating PP2A. HN also inhibited apoptosis and reduced the oxidative stress induced by Aβ(1-42). These findings provide novel mechanisms of action for the ability of HN to protect against Aβ(1-42)-induced AD-like pathological changes and memory deficits.

  19. Inattention, working memory, and academic achievement in adolescents referred for attention deficit/hyperactivity disorder (ADHD).

    Science.gov (United States)

    Rogers, Maria; Hwang, Heungsun; Toplak, Maggie; Weiss, Margaret; Tannock, Rosemary

    2011-01-01

    This study investigated the role of inattention and working memory in predicting academic achievement in 145 adolescents aged 13 to 18 referred for attention deficit/hyperactivity disorder (ADHD). Path analysis was used to examine whether auditory-verbal and visual-spatial working memory would mediate the relationships between classroom inattention symptoms and achievement outcomes. Results provide support for the mediational model. Behavioral inattention significantly predicted both auditory-verbal and visual-spatial working memory performance. Auditory-verbal working memory was strongly associated with adolescents' achievement in reading and mathematics, while visual-spatial working memory was only associated with achievement in mathematics. The path from inattention symptoms to reading was partially mediated by the working memory variables, but the path from inattention to mathematics was not mediated by working memory. The proposed model demonstrated a good fit to the data and explained a substantial amount of variance in the adolescents' achievement outcomes. These findings imply that working memory is a risk factor for academic failure for adolescents with attentional problems.

  20. Training of attention and memory deficits in children with acquired brain injury

    DEFF Research Database (Denmark)

    Madsen Sjö, Nina; Spellerberg, Stine Marie; Weidner, Susanne

    2010-01-01

    This pilot study concerns cognitive rehabilitation of children with acquired brain injury (ABI). Aim: The aim is threefold; to determine (1) whether the Amsterdam Memory and Attention Training for Children (AMAT-C) programme for children with ABI can be integrated in the child’s school, (2) whether...... supervision in the school-setting maintains the child’s motivation throughout the training programme and (3) whether positive changes in memory, attention and executive functions are found with this implementation of the training method. Methods: Seven children with memory and ⁄ or attention deficits after....... The children showed significant improvements in neuropsychological subtests, primarily in tests of learning and memory. No overall change in executive functions was noted. Conclusion: Provision of AMAT-C training and supervision at the child’s school appears to ensure (1) satisfaction with the programme, (2...

  1. Mitigation of chronic unpredictable stress–induced cognitive deficits ...

    African Journals Online (AJOL)

    against concomitant cognitive dysfunction in chronically stressed mice, and the role of LBP in .... Figure 2: LBSP treatment reversed CUS-induced spatial learning and memory damage in MWMT. NOTE: (a) The probe tracks of Probe .... addition to remarkable neuronal morphological damage in CA1 region in hippocampus ...

  2. Olfactory discrimination and memory deficits in the Flinders Sensitive Line rodent model of depression.

    Science.gov (United States)

    Cook, A; Pfeiffer, L-M; Thiele, S; Coenen, V A; Döbrössy, M D

    2017-10-01

    Major Depressive Disorder (MDD) is a heterogeneous psychiatric disorder with broad symptomatic manifestations. The current study examined, for the first time, olfactory memory and discrimination in the Flinders Sensitive Line (FSL) rodent model of depression. Male FSL rats and controls were trained on an Olfactory Discrimination (OD) and a Social Interaction (SI) test. On the OD test, the FSL and controls performed similarly at the shortest inter-trial interval (5min), however, with extended delay of 30min, the FSLs had a recall and odour discrimination deficit. At the longest delay (60min) both groups performed poorly. The FSL rats i.) had a deficit in olfactory discrimination suggesting impairment in olfactory memory and recall; ii.) were less likely to socialize with unfamiliar rats. The data suggests that FSL animals have an impaired olfactory information processing capacity. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Spatial memory and learning deficits after experimental pneumococcal meningitis in mice.

    Science.gov (United States)

    Wellmer, A; Noeske, C; Gerber, J; Munzel, U; Nau, R

    2000-12-22

    Survivors of bacterial meningitis frequently suffer from long-term sequelae, particularly from learning and memory deficits. For this reason, spatial memory and learning was studied in a mouse model of ceftriaxone-treated Streptococcus pneumoniae meningitis. Persistent deficits of spatial learning despite normal motor function were observed in mice infected with 10(4) colony-forming units (CFU) in 25 microl of saline into the right forebrain in comparison to mice treated with an equal amount of saline. Survivors of meningitis performed significantly worse in memorizing a hidden platform in a Morris water maze. After 2 weeks, the difference between post-meningitis and control mice diminished. Yet, when the platform was moved after 180 days, learning of the new location was still strongly impaired in mice surviving meningitis.

  4. Age-Related Deficits in Reality Monitoring of Action Memories

    Science.gov (United States)

    McDaniel, Mark A.; Lyle, Keith B.; Butler, Karin M.; Dornburg, Courtney C.

    2008-01-01

    We describe three theoretical accounts of age-related increases in falsely remembering that imagined actions were performed (Thomas & Bulevich, 2006). To investigate these accounts and further explore age-related changes in reality monitoring of action memories, we used a new paradigm in which actions were (a) imagined-only (b) actually performed, or (c) both imagined and performed. Older adults were more likely than younger adults to misremember the source of imagined-only actions, with older adults’ more often specifying that the action was imagined and also that it was performed. For both age groups, as repetitions of the imagined-only events increased, illusions that the actions were only performed decreased. These patterns suggest that both older and younger adults utilize qualitative characteristics when making reality-monitoring judgments and that repeated imagination produces richer records of both sensory details and cognitive operations. However, sensory information derived from imagination appears to be more similar to that derived from performance for older than younger adults. PMID:18808253

  5. Auditory and Visual Working Memory Functioning in College Students with Attention-Deficit/Hyperactivity Disorder and/or Learning Disabilities.

    Science.gov (United States)

    Liebel, Spencer W; Nelson, Jason M

    2017-12-01

    We investigated the auditory and visual working memory functioning in college students with attention-deficit/hyperactivity disorder, learning disabilities, and clinical controls. We examined the role attention-deficit/hyperactivity disorder subtype status played in working memory functioning. The unique influence that both domains of working memory have on reading and math abilities was investigated. A sample of 268 individuals seeking postsecondary education comprise four groups of the present study: 110 had an attention-deficit/hyperactivity disorder diagnosis only, 72 had a learning disability diagnosis only, 35 had comorbid attention-deficit/hyperactivity disorder and learning disability diagnoses, and 60 individuals without either of these disorders comprise a clinical control group. Participants underwent a comprehensive neuropsychological evaluation, and licensed psychologists employed a multi-informant, multi-method approach in obtaining diagnoses. In the attention-deficit/hyperactivity disorder only group, there was no difference between auditory and visual working memory functioning, t(100) = -1.57, p = .12. In the learning disability group, however, auditory working memory functioning was significantly weaker compared with visual working memory, t(71) = -6.19, p auditory or visual working memory functioning differences between participants with either a predominantly inattentive type or a combined type diagnosis. Visual working memory did not incrementally contribute to the prediction of academic achievement skills. Individuals with attention-deficit/hyperactivity disorder did not demonstrate significant working memory differences compared with clinical controls. Individuals with a learning disability demonstrated weaker auditory working memory than individuals in either the attention-deficit/hyperactivity or clinical control groups. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Semantic memory deficits are associated with pica in individuals with acquired brain injury.

    Science.gov (United States)

    Funayama, Michitaka; Muramatsu, Taro; Koreki, Akihiro; Kato, Motoichiro; Mimura, Masaru; Nakagawa, Yoshitaka

    2017-06-30

    Although pica is one of the most prominent signs in individuals with severe cognitive impairment, the mechanisms and neural basis for pica have not been well elucidated. To address this issue, patients with acquired brain injury who showed pica and hyperorality were investigated. Eleven patients with pica, i.e., individuals who eat non-food items, and eight patients with hyperorality but who never eat non-food items were recruited. The cognitive and behavioral assessments and neural substrates of the two groups were compared. For basic cognitive and behavioral functions, two kinds of mental state examination-the mini-mental state examination and the new clinical scale for rating of mental states of the elderly-were administered. For pica-related behavioral features, frontal release signs, semantic memory deficits, and changes in eating behaviors were compared. Compared with the hyperorality group, the pica group had more severe semantic memory deficits and fewer frontal release signs, whereas there was no significant difference in changes in eating behaviors. Individuals in the pica group always had a lesion in the posterior part of the middle temporal gyrus. These findings suggest that semantic memory deficits following temporal lobe damage are associated with pica. Copyright © 2017. Published by Elsevier B.V.

  7. Choline and Working Memory Training Improve Cognitive Deficits Caused by Prenatal Exposure to Ethanol

    Directory of Open Access Journals (Sweden)

    Jaylyn Waddell

    2017-09-01

    Full Text Available Prenatal ethanol exposure is associated with deficits in executive function such as working memory, reversal learning and attentional set shifting in humans and animals. These behaviors are dependent on normal structure and function in cholinergic brain regions. Supplementation with choline can improve many behaviors in rodent models of fetal alcohol spectrum disorders and also improves working memory function in normal rats. We tested the hypothesis that supplementation with choline in the postnatal period will improve working memory during adolescence in normal and ethanol-exposed animals, and that working memory engagement during adolescence will transfer to other cognitive domains and have lasting effects on executive function in adulthood. Male and female offspring of rats fed an ethanol-containing liquid diet (ET; 3% v/v or control dams given a non-ethanol liquid diet (CT were injected with choline (Cho; 100 mg/kg or saline (Sal once per day from postnatal day (P 16–P30. Animals were trained/tested on a working memory test in adolescence and then underwent attentional set shifting and reversal learning in young adulthood. In adolescence, ET rats required more training to reach criterion than CT-Sal. Choline improved working memory performance for both CT and ET animals. In young adulthood, ET animals also performed poorly on the set shifting and reversal tasks. Deficits were more robust in ET male rats than female ET rats, but Cho improved performance in both sexes. ET male rats given a combination of Cho and working memory training in adolescence required significantly fewer trials to achieve criterion than any other ET group, suggesting that early interventions can cause a persistent improvement.

  8. Choline and Working Memory Training Improve Cognitive Deficits Caused by Prenatal Exposure to Ethanol.

    Science.gov (United States)

    Waddell, Jaylyn; Mooney, Sandra M

    2017-09-29

    Prenatal ethanol exposure is associated with deficits in executive function such as working memory, reversal learning and attentional set shifting in humans and animals. These behaviors are dependent on normal structure and function in cholinergic brain regions. Supplementation with choline can improve many behaviors in rodent models of fetal alcohol spectrum disorders and also improves working memory function in normal rats. We tested the hypothesis that supplementation with choline in the postnatal period will improve working memory during adolescence in normal and ethanol-exposed animals, and that working memory engagement during adolescence will transfer to other cognitive domains and have lasting effects on executive function in adulthood. Male and female offspring of rats fed an ethanol-containing liquid diet (ET; 3% v / v ) or control dams given a non-ethanol liquid diet (CT) were injected with choline (Cho; 100 mg/kg) or saline (Sal) once per day from postnatal day (P) 16-P30. Animals were trained/tested on a working memory test in adolescence and then underwent attentional set shifting and reversal learning in young adulthood. In adolescence, ET rats required more training to reach criterion than CT-Sal. Choline improved working memory performance for both CT and ET animals. In young adulthood, ET animals also performed poorly on the set shifting and reversal tasks. Deficits were more robust in ET male rats than female ET rats, but Cho improved performance in both sexes. ET male rats given a combination of Cho and working memory training in adolescence required significantly fewer trials to achieve criterion than any other ET group, suggesting that early interventions can cause a persistent improvement.

  9. Binge drinking during adolescence and young adulthood is associated with deficits in verbal episodic memory.

    Science.gov (United States)

    Carbia, Carina; Cadaveira, Fernando; Caamaño-Isorna, Francisco; Rodríguez-Holguín, Socorro; Corral, Montse

    2017-01-01

    Binge drinking (BD), a harmful pattern of alcohol consumption, is common during adolescence. Young adults with alcohol use disorders exhibit hippocampal alterations and episodic memory deficits. However, it is not known how these difficulties progress in community BD adolescents. Our objective was to analyze the relationship between BD trajectory and verbal episodic memory during the developmental period spanning from adolescence and to early adulthood. An initial sample of 155 male and female first-year university students with no other risk factors were followed over six years. Participants were classified as stable non-BDs, stable BDs and ex-BDs according to the third AUDIT item. At baseline, participants comprised 36 ♂/ 40 ♀ non-BDs (18.58 years), 40 ♂/ 39 ♀ BDs (18.87 years), and at the third follow-up, they comprised 8 ♂/ 8 ♀ stable non-BDs (25.49 years), 2 ♂/ 2 ♀ stable BDs (25.40) and 8 ♂/ 12 ♀ ex-BDs (24.97 years). Episodic memory was assessed four times with the Logical Memory subtest (WMS-III) and the Rey Auditory Verbal Learning Test (RAVLT). Generalized linear mixed models were applied. The results showed that, relative to non-BDs, stable BDs presented difficulties in immediate and delayed recall in the Logical Memory subtest. These difficulties remained stable over time. The short-term ex-BDs continued to display difficulties in immediate and delayed recall in the Logical Memory subtest, but long-term ex-BDs did not. The effects were not influenced by age of alcohol onset, frequency of cannabis use, tobacco use or psychopathological distress. In conclusion, BD during adolescence and young adulthood is associated with episodic memory deficits. Abandoning the BD pattern may lead to partial recovery. These findings are consistent with the vulnerability of the adolescent hippocampus to the neurotoxic effects of alcohol.

  10. Spatial Working Memory Deficits Represent a Core Challenge for Rehabilitating Neglect

    Science.gov (United States)

    Striemer, Christopher L.; Ferber, Susanne; Danckert, James

    2013-01-01

    Left neglect following right hemisphere injury is a debilitating disorder that has proven extremely difficult to rehabilitate. Traditional models of neglect have focused on impaired spatial attention as the core deficit and as such, most rehabilitation methods have tried to improve attentional processes. However, many of these techniques (e.g., visual scanning training, caloric stimulation, neck muscle vibration) produce only short-lived effects, or are too uncomfortable to use as a routine treatment. More recently, many investigators have begun examining the beneficial effects of prism adaptation for the treatment of neglect. Although prism adaptation has been shown to have some beneficial effects on both overt and covert spatial attention, it does not reliably alter many of the perceptual biases evident in neglect. One of the challenges of neglect rehabilitation may lie in the heterogeneous nature of the deficits. Most notably, a number of researchers have shown that neglect patients present with severe deficits in spatial working memory (SWM) in addition to their attentional impairments. Given that SWM can be seen as a foundational cognitive mechanism, critical for a wide range of other functions, any deficit in SWM memory will undoubtedly have severe consequences. In the current review we examine the evidence for SWM deficits in neglect and propose that it constitutes a core component of the syndrome. We present preliminary data which suggest that at least one current rehabilitation method (prism adaptation) has no effect on SWM deficits in neglect. Finally, we end by reviewing recent work that examines the effectiveness of SWM training and how SWM training may prove to be a useful avenue for future rehabilitative efforts in patients with neglect. PMID:23818880

  11. Spatial working memory deficits represent a core challenge for rehabilitating neglect.

    Directory of Open Access Journals (Sweden)

    Christopher eStriemer

    2013-06-01

    Full Text Available Left neglect following right hemisphere injury is a debilitating disorder that has proven extremely difficult to rehabilitate. Traditional models of neglect have focused on impaired spatial attention as the core deficit and as such, most rehabilitation methods have tried to improve attentional processes. However, many of these techniques (e.g., visual scanning training, caloric stimulation, neck muscle vibration produce only short-lived effects, or are too uncomfortable to use as a routine treatment. More recently, many investigators have begun examining the beneficial effects of prism adaptation for the treatment of neglect. Although prism adaptation has been shown to have some beneficial effects on both overt and covert spatial attention, it does not reliably alter many of the perceptual biases evident in neglect. One of the challenges of neglect rehabilitation may lie in the heterogeneous nature of the deficits. Most notably, a number of researchers have shown that neglect patients present with severe deficits in spatial working memory (SWM in addition to their attentional impairment. Given that SWM can be seen as a foundational cognitive mechanism, critical for a wide range of other functions, any deficit in SWM memory will undoubtedly have severe consequences. In the current review we examine the evidence for SWM deficits in neglect and propose that it constitutes a core component of the syndrome. We present preliminary data which suggest that at least one current rehabilitation method (prism adaptation has no effect on SWM deficits in neglect. Finally, we end by reviewing recent work that examines the effectiveness of SWM training and how SWM training may prove to be a useful avenue for future rehabilitative efforts in patients with neglect.

  12. Will Working Memory Training Generalize to Improve Off-Task Behavior in Children with Attention-Deficit/Hyperactivity Disorder?

    OpenAIRE

    Green, Chloe T.; Long, Debra L.; Green, David; Iosif, Ana-Maria; Dixon, J. Faye; Miller, Meghan R.; Fassbender, Catherine; Schweitzer, Julie B.

    2012-01-01

    Computerized working memory and executive function training programs designed to target specific impairments in executive functioning are becoming increasingly available, yet how well these programs generalize to improve functional deficits in disorders, such as attention-deficit/hyperactivity disorder (ADHD), beyond the training context is not well-established. The aim of this study was to examine the extent to which working memory (WM) training in children with ADHD would diminish a core dy...

  13. Exposure to radiation accelerates normal brain aging and produces deficits in spatial learning and memory

    Science.gov (United States)

    Shukitt-Hale, B.; Casadesus, G.; Carey, A.; Rabin, B. M.; Joseph, J. A.

    Previous studies have shown that radiation exposure, particularly to particles of high energy and charge (HZE particles), produces deficits in spatial learning and memory. These adverse behavioral effects are similar to those seen in aged animals. It is possible that these shared effects may be produced by the same mechanism; oxidative stress damage to the central nervous system caused by an increased release of reactive oxygen species is likely responsible for the deficits seen in aging and following irradiation. Both aged and irradiated rats display cognitive impairment in tests of spatial learning and memory such as the Morris water maze and the radial arm maze. These rats have decrements in the ability to build spatial representations of the environment and they utilize non-spatial strategies to solve tasks. Furthermore, they show a lack of spatial preference, due to a decline in the ability to process or retain place (position of a goal with reference to a "map" provided by the configuration of numerous cues in the environment) information. These declines in spatial memory occur in measures dependent on both reference and working memory, and in the flexibility to reset mental images. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. Supported by NASA Grants NAG9-1190 and NAG9-1529

  14. Everyday Prospective Memory and Executive Function Deficits Associated with Exposure to Second-Hand Smoke

    Directory of Open Access Journals (Sweden)

    Thomas M. Heffernan

    2013-01-01

    Full Text Available This study explored whether exposure to second-hand smoke (SHS has a detrimental impact upon everyday memory in two groups of non-smokers; one which reported regular exposure to SHS and one that reported never having been exposed to SHS. Thirty-four non-smokers who reported having been regularly exposed to SHS (SHS group and 34 non-smokers who reported never having been exposed to SHS (non-SHS group were compared on self-reports of prospective memory (PM: remembering future intentions and/or activities and executive function (EF: those processes involved in attention, multitasking and decision-making. The Prospective and Retrospective Memory Questionnaire (PRMQ assessed everyday PM lapses; the Executive Function Questionnaire (EFQ assessed self-reported problems in EF; a drug-use questionnaire and a mood questionnaire were also administered. Two univariate ANCOVAs were applied to the PM and EF data, controlling for between-group differences in age, weekly alcohol use, anxiety and depression scores, and self-reported retrospective memory scores. The SHS group reported significantly more lapses on the PRMQ and more deficits on the EFQ than the non-SHS group. These findings provide new insights into PM and EF deficits associated with prolonged exposure to SHS in a group of non-smokers. Possible explanations and suggestions for future research are also considered.

  15. Frequency and Severity of Semantic Deficits in a Consecutive Memory Clinic Cohort

    DEFF Research Database (Denmark)

    Vogel, Asmus; Johannsen, Peter; Stokholm, Jette

    2014-01-01

    Background/Aim: Semantic memory deficits have been shown in dementia and mild cognitive impairment (MCI) by group comparisons. The aim of this study is to investigate the frequency of impairments on tests with semantic content in patients with dementia, MCI (amnestic and non-amnestic) and affective...... disorders. Methods: A Famous faces test, Boston Naming Test and Category fluency were applied in 114 consecutive memory clinic patients and 95 healthy participants (all participants were 60 years old or older; dementia/MCI patients had Mini-Mental State Examination scores ≥20). Results: Fifty-three patients......). However, patients with affective disorders also had mild impairments on tests tapping semantic memory (25% were impaired on the most sensitive tests). Impairments on the Famous faces test were more frequently found in dementia and MCI as compared to patients with affective disorders. Conclusion: Short...

  16. Long-term effects of brief hypoxia due to cardiac arrest: Hippocampal reductions and memory deficits.

    Science.gov (United States)

    Stamenova, Vess; Nicola, Raneen; Aharon-Peretz, Judith; Goldsher, Dorith; Kapeliovich, Michael; Gilboa, Asaf

    2018-02-21

    To examine the effects of brief hypoxia (memory and executive functions tasks. Patients after out-of-hospital cardiac arrest (CA) (n = 9), who were deemed neurologically intact on discharge, were compared to matched patients with myocardial infarction (MI) (n = 9). A battery of clinical and experimental memory and executive functions neuropsychological tests were administered and MRI scans for all patients were collected. Measures of subcortical and cortical volumes and cortical thickness were obtained using FreeSurfer. Manual segmentations of the hippocampus were also performed. APACHE-II scores were calculated based on metrics collected at admission to ICCU for all patients. Significant differences between the two groups were observed on several verbal memory tests. Both hippocampi were significantly reduced (p memory tasks, including recollection. Hippocampal volumes and several memory measures (but not other cognitive domains) were strongly correlated with APACHE-II scores on admission in the CA group, but not in the MI group CONCLUSIONS: Chronic patients with cardiac arrest who were discharged from hospital in "good neurological condition" showed an average of 10% reduction in hippocampal volume bilaterally and significant verbal memory deficits relative to matched controls with myocardial infarction, suggesting even brief hypoxic periods suffice to lead to specific hippocampal damage. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Visual short-term memory deficits associated with GBA mutation and Parkinson's disease.

    Science.gov (United States)

    Zokaei, Nahid; McNeill, Alisdair; Proukakis, Christos; Beavan, Michelle; Jarman, Paul; Korlipara, Prasad; Hughes, Derralynn; Mehta, Atul; Hu, Michele T M; Schapira, Anthony H V; Husain, Masud

    2014-08-01

    Individuals with mutation in the lysosomal enzyme glucocerebrosidase (GBA) gene are at significantly high risk of developing Parkinson's disease with cognitive deficit. We examined whether visual short-term memory impairments, long associated with patients with Parkinson's disease, are also present in GBA-positive individuals-both with and without Parkinson's disease. Precision of visual working memory was measured using a serial order task in which participants observed four bars, each of a different colour and orientation, presented sequentially at screen centre. Afterwards, they were asked to adjust a coloured probe bar's orientation to match the orientation of the bar of the same colour in the sequence. An additional attentional 'filtering' condition tested patients' ability to selectively encode one of the four bars while ignoring the others. A sensorimotor task using the same stimuli controlled for perceptual and motor factors. There was a significant deficit in memory precision in GBA-positive individuals-with or without Parkinson's disease-as well as GBA-negative patients with Parkinson's disease, compared to healthy controls. Worst recall was observed in GBA-positive cases with Parkinson's disease. Although all groups were impaired in visual short-term memory, there was a double dissociation between sources of error associated with GBA mutation and Parkinson's disease. The deficit observed in GBA-positive individuals, regardless of whether they had Parkinson's disease, was explained by a systematic increase in interference from features of other items in memory: misbinding errors. In contrast, impairments in patients with Parkinson's disease, regardless of GBA status, was explained by increased random responses. Individuals who were GBA-positive and also had Parkinson's disease suffered from both types of error, demonstrating the worst performance. These findings provide evidence for dissociable signature deficits within the domain of visual short

  18. Propranolol–induced Impairment of Contextual Fear Memory Reconsolidation in Rats: A Similar Effect on Weak and Strong Recent and Remote Memories

    Directory of Open Access Journals (Sweden)

    Fatemeh Taherian

    2014-07-01

    Full Text Available Introduction: Previous studies have demonstrated that the &beta-adrenergic receptor antagonist propranolol impairs fear memory reconsolidation in experimental animals. There are experimental parameters such as the age and the strength of memory that can interact with pharmacological manipulations of memory reconsolidation. In this study, we investigated the ability of the age and the strength of memory to influence the disrupting effects of propranolol on fear memory reconsolidation in rats. Methods: The rats were trained in a contextual fear conditioning using two (weak training or five (strong training footshocks (1mA. Propranolol (10mg/kg injection was immediately followed retrieval of either a one-day recent (weak or strong or 36-day remote (weak or strong contextual fear memories. Results: We found that propranolol induced a long-lasting impairment of subsequent expression of recent and remote memories with either weak or strong strength. We also found no memory recovery after a weak reminder shock. Furthermore, no significant differences were found on the amount of memory deficit induced by propranolol among memories with different age and strength. Discussion: Our data suggest that the efficacy of propranolol in impairing fear memory reconsolidation is not limited to the age or strength of the memory.

  19. Green Tea Extract Ameliorates Learning and Memory Deficits in Ischemic Rats via Its Active Component Polyphenol Epigallocatechin-3-gallate by Modulation of Oxidative Stress and Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Kuo-Jen Wu

    2012-01-01

    Full Text Available Ischemic stroke results in brain damage and behavioral deficits including memory impairment. Protective effects of green tea extract (GTex and its major functional polyphenol (−-epigallocatechin gallate (EGCG on memory were examined in cerebral ischemic rats. GTex and EGCG were administered 1 hr before middle cerebral artery ligation in rats. GTex, EGCG, and pentoxifylline (PTX significantly improved ishemic-induced memory impairment in a Morris water maze test. Malondialdehyde (MDA levels, glutathione (GSH, and superoxide dismutase (SOD activity in the cerebral cortex and hippocampus were increased by long-term treatment with GTex and EGCG. Both compounds were also associated with reduced cerebral infraction breakdown of MDA and GSH in the hippocampus. In in vitro experiments, EGCG had anti-inflammatory effects in BV-2 microglia cells. EGCG inhibited lipopolysaccharide- (LPS- induced nitric oxide production and reduced cyclooxygenase-2 and inducible nitric oxide synthase expression in BV-2 cells. GTex and its active polyphenol EGCG improved learning and memory deficits in a cerebral ischemia animal model and such protection may be due to the reduction of oxidative stress and neuroinflammation.

  20. The Effects of Incentives on Visual-Spatial Working Memory in Children with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Shiels, Keri; Hawk, Larry W., Jr.; Lysczek, Cynthia L.; Tannock, Rosemary; Pelham, William E., Jr.; Spencer, Sarah V.; Gangloff, Brian P.; Waschbusch, Daniel A.

    2008-01-01

    Working memory is one of several putative core neurocognitive processes in attention-deficit/hyperactivity disorder (ADHD). The present work seeks to determine whether visual-spatial working memory is sensitive to motivational incentives, a laboratory analogue of behavioral treatment. Participants were 21 children (ages 7-10) with a diagnosis of…

  1. Memory deficit associated with worse functional trajectories in older adults in low-vision rehabilitation for macular disease.

    Science.gov (United States)

    Whitson, Heather E; Whitaker, Diane; Sanders, Linda L; Potter, Guy G; Cousins, Scott W; Ansah, Deidra; McConnell, Eleanor; Pieper, Carl F; Landerman, Lawrence; Steffens, David C; Cohen, Harvey J

    2012-11-01

    To examine whether performance on a brief memory test is related to functional outcomes in older individuals undergoing low-vision rehabilitation (LVR) for macular disease. Observational cohort study of individuals receiving outpatient LVR. Academic center. Ninety-one individuals (average age 80.1) with macular disease. Memory was assessed at baseline using a 10-word list; memory deficit was defined as immediate recall of two or fewer words. Vision-related function was measured using the 25-item Visual Function Questionnaire (VFQ-25) administered at baseline and during subsequent interviews (mean follow-up, 115 days). Linear mixed models were constructed to compare average trajectories of four VFQ-25 subscales: near activities, distance activities, dependency, and role difficulty. The 29.7% of participants with memory deficits tended to decline in ability to accomplish activities that involved near vision. Controlling for age, sex, and education, the functional trajectory of participants with memory deficit differed significantly from that of those with better memory (P = .002), who tended to report improvements in ability to accomplish near activities. Of older adults receiving LVR for macular disease, those with memory deficits experienced worse functional trajectories in their ability to perform specific visually mediated tasks. A brief memory screen may help explain variability in rehabilitation outcomes and identify individuals who might require special accommodations. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

  2. Predictors of Memory Deficits in Adolescents and Young Adults with Congenital Heart Disease Compared to Healthy Controls

    Directory of Open Access Journals (Sweden)

    Nancy A. Pike

    2016-10-01

    Full Text Available Introduction: Adolescents and young adults with congenital heart disease [CHD] show a range of memory deficits, which can dramatically impact their clinical outcomes and quality of life. However, few studies have identified predictors of these memory changes. The purpose of this investigation was to identify predictors of memory deficits in adolescents and young adults with CHD after surgical palliation compared to healthy controls. Method: 156 adolescents and young adults [80 CHD and 76 controls; age 14-21 years] were recruited and administered an instrument to assess memory [Wide Range Assessment of Memory and Learning 2nd Edition – general memory index (GMI score] and completed questionnaires that measure anxiety, depression, sleepiness, health status, and self-efficacy. Descriptive and non-parametric statistics were used to assess group differences, and logistic regression to identify predictors of memory deficits. Results: CHD subjects consisted of 58% males, median age 17 years, 41% Hispanic, and medians of 2 previous heart surgeries and 14 years since last surgery. Memory deficits [GMI < 85] were identified in 50% CHD compared to 4% healthy controls [median GMI 85 vs. 108, p <0.001]. Of GMI subscale medians, CHD subjects had significantly worse memory performance vs. healthy controls [verbal 88 vs. 105, p <0.001; attention 88 vs. 109, p<0.001; working memory 86 vs. 108, p <0.001]. No significant differences appeared between groups for visual memory. Multiple clinical and psychosocial factors were identified which were statistically different on bivariate analyses between the subjects with and without memory deficits. By multivariate analysis, male gender, number of surgeries, anxiety, and self-efficacy emerged as independent predictors of memory deficits. Conclusion: Adolescents and young adults with CHD, more than a decade since their last surgery, show significant verbal, attention and working memory deficits over controls. To enhance

  3. Neuroleptic-induced deficit syndrome in bipolar disorder with psychosis

    Directory of Open Access Journals (Sweden)

    Ueda S

    2016-02-01

    Full Text Available Satoshi Ueda,1 Takeshi Sakayori,1 Ataru Omori,2 Hajime Fukuta,3 Takashi Kobayashi,3 Kousuke Ishizaka,1 Tomoyuki Saijo,4 Yoshiro Okubo1 1Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan; 2Tamachuo Hospital, Tokyo, Japan; 3Kurumegaoka Hospital, Tokyo, Japan; 4Saijo Clinic, Tokyo, Japan Abstract: Neuroleptics can induce not only physical adverse effects but also mental effects that produce deficit status in thought, affect, cognition, and behavior. This condition is known as neuroleptic-induced deficit syndrome (NIDS, which includes apathy, lack of initiative, anhedonia, indifference, blunted affect, and reduced insight into disease. Although this old concept now appears almost forgotten, neuroleptics, whether typical or atypical, can make depression or bipolar disorder resemble other more refractory conditions, readily leading to mistaken diagnosis and inappropriate treatment. The authors describe three cases of NIDS superimposed on depressive phase in bipolar disorder with psychosis, where the attending psychiatrist’s failure to recognize NIDS prevented patients from receiving effective treatment and achieving remission. All cases achieved remission after reduction of neuroleptics and intensive therapy, including electroconvulsive therapy, for bipolar depression. The concept of NIDS was originally introduced for schizophrenia, and it has rarely been highlighted in other diseases. In recent years, however, atypical antipsychotics are being more often administered to patients with bipolar disorder. Psychiatrists, therefore, should also remember and exercise caution regarding NIDS in the pharmacotherapy of bipolar disorder with and without psychosis. The authors believe that the concept of NIDS needs to be reappraised in current psychiatry. Keywords: neuroleptic-induced deficit syndrome (NIDS, bipolar disorder, psychosis, atypical antipsychotics, electroconvulsive therapy

  4. "Gadd45b" Knockout Mice Exhibit Selective Deficits in Hippocampus-Dependent Long-Term Memory

    Science.gov (United States)

    Leach, Prescott T.; Poplawski, Shane G.; Kenney, Justin W.; Hoffman, Barbara; Liebermann, Dan A.; Abel, Ted; Gould, Thomas J.

    2012-01-01

    Growth arrest and DNA damage-inducible [beta] ("Gadd45b") has been shown to be involved in DNA demethylation and may be important for cognitive processes. "Gadd45b" is abnormally expressed in subjects with autism and psychosis, two disorders associated with cognitive deficits. Furthermore, several high-throughput screens have identified "Gadd45b"…

  5. Neural activity changes underlying the working memory deficit in alpha-CaMKII heterozygous knockout mice

    Directory of Open Access Journals (Sweden)

    Naoki Matsuo

    2009-09-01

    Full Text Available The alpha-isoform of calcium/calmodulin-dependent protein kinase II (α-CaMKII is expressed abundantly in the forebrain and is considered to have an essential role in synaptic plasticity and cognitive function. Previously, we reported that mice heterozygous for a null mutation of α-CaMKII (α-CaMKII+/- have profoundly dysregulated behaviors including a severe working memory deficit, which is an endophenotype of schizophrenia and other psychiatric disorders. In addition, we found that almost all the neurons in the dentate gyrus (DG of the mutant mice failed to mature at molecular, morphological and electrophysiological levels. In the present study, to identify the brain substrates of the working memory deficit in the mutant mice, we examined the expression of the immediate early genes (IEGs, c-Fos and Arc, in the brain after a working memory version of the eight-arm radial maze test. c-Fos expression was abolished almost completely in the DG and was reduced significantly in neurons in the CA1 and CA3 areas of the hippocampus, central amygdala, and medial prefrontal cortex (mPFC. However, c-Fos expression was intact in the entorhinal and visual cortices. Immunohistochemical studies using arc promoter driven dVenus transgenic mice demonstrated that arc gene activation after the working memory task occurred in mature, but not immature neurons in the DG of wild-type mice. These results suggest crucial insights for the neural circuits underlying spatial mnemonic processing during a working memory task and suggest the involvement of α-CaMKII in the proper maturation and integration of DG neurons into these circuits.

  6. Role of decreased Plasma Tryptophan in memory deficits observed in Type-I diabetes

    International Nuclear Information System (INIS)

    Ahmad, S.; Tabassum, S.; Haider, S.

    2013-01-01

    Objective: To investigate the relationship between plasma tryptophan and the occurrence of memory dysfunctions in male and female type 1 diabetics. Methods: The case-control study was conducted at two urban healthcare facilities in Karachi from January to June 2009, and comprised 100 diabetic subjects of among whom were 50 men and 50 women. The controls were also similar in number and gender. A questionnaire was used to evaluate the memory impairment in the subjects. Plasma tryptophan was determined by high performance liquid chromatography with ultra-violet method. Students t-test was used to analyse tryptophan data. Results: There was considerable memory impairment in the cases (n=40) compared to the controls (n=5). Results also showed a significant (p<0.01) decrease in plasma tryptophan levels in both male and female diabetic patients. Conclusions: Diabetic subjects exhibited occurrence of memory impairment with concomitant decline in plasma tryptophan levels. The findings indicate that decreased brain uptake of tryptophan and lowered brain 5-hydroxytryptamine levels may be responsible for the memory deficits seen in diabetics. (author)

  7. Functional MRI study of verbal working memory in children with attention deficit hyperactivity disorder

    International Nuclear Information System (INIS)

    Lu Youran; Geng Daoying; Feng Xiaoyuan; Du Yasong; Zhao Zhimin

    2006-01-01

    Objective: To study the verbal working memory of children with attention deficit hyperactivity disorder (ADHD) as well as to explore the characteristics of functional areas of verbal working memory with blood oxygenation level dependent functional magnetic resonance imaging (fMRI). Method: Eighteen children were selected in the study. There were 9 ADHD children with inattention subtype and 9 healthy subjects. All patients and healthy subjects completed the cognitive examination and the block- designed N-block verbal working memory task using a GE 3.0 T MR. Data were analyzed by AFNI software. Result: The neural activations of ADHD's children are lower than that of control under verbal working memory. Especially in the areas of bilateral middle frontal gyri and inferior frontal gyri, bilateral superior parietal lobules and inferior parietal lobules, right basal ganglia in the 1-BACK task. And bilateral middle frontal gyri and inferior frontal gyri, bilateral superior parietal lobules, left cortex inferior parietallobule, right basal ganglia, anterior cingulatecortex in the 2-BACK task. Conclusion: The hypofunctional areas of verbal working memory (including bilateral dorsolateral prefrontal cortex and parietal cortex) can be seen in the ADHD children especially who also has lower activation of anterior cingulate cortex under 2-BACK task. (authors)

  8. Numa Manson on velocity deficits and detonation stability. An invited memorial lecture presented at ICDERS 21

    Science.gov (United States)

    Murray, S. B.

    2008-09-01

    This memorial paper pays tribute to Professor Numa Manson’s contributions to the understanding of detonation velocity deficits and wave stability. Manson and his colleague Guénoche postulated that a velocity deficit exists in a tube because the chemical reactions are inhibited in a thin layer adjacent to the tube walls. The hydrodynamic theory of detonation was modified to account for this, and it was shown that the deficit varies inversely with the tube diameter. Manson and his students measured detonation velocities in tubes of various diameter. An estimate of the detonation velocity for an infinite tube diameter was obtained by plotting the velocity against the reciprocal of the tube diameter, {φ^{-1}} , and extrapolating the line through the data to {φ^{-1}=0} . The relative contributions of tube geometry and surface roughness to the deficits were systematically studied. Manson was also one of the early investigators to shed light on the cellular structure of detonation by reporting “vibratory phenomena” seen as striations in streak schlieren photographs. An attempt was made to relate this phenomenon to “dispersions” in the propagation velocity and hence the wave stability. The author has extended Manson’s work by investigating detonations in tubes with yielding walls. Whereas boundary layers were responsible for the gasdynamic expansion and deficits in Manson’s rigid tubes, it was the moving boundaries that caused similar effects in the author’s investigations. The author has repeated the “nozzle” analysis of Fay and Dabora using the detonation cell length as the relevant chemical kinetic length scale, and found reasonable agreement between his experimental results and the model. When the Poitiers data are reinterpreted in light of the modified model, the trends are described quite well. More recent studies have shown that the measured deficits for mixtures characterized by irregular cellular structures do not agree with the Fay

  9. Deficit

    CERN Multimedia

    2002-01-01

    UCL's former provost, Sir Derek Roberts, has been drafted in for a year to run the college. UCL is expected to have a 6 million pounds deficit this year and up to a 10 million pounds deficit next year. Sir Christopher Llewellyn-Smith took over at UCL nearly 4 years ago and decided then that the finanical situation was serious enough to warrant a reduction in the vast expansion policy undertaken by his predecessor (1 page).

  10. Selective deficit of spatial short-term memory: Role of storage and rehearsal mechanisms.

    Science.gov (United States)

    Bonnì, Sonia; Perri, Roberta; Fadda, Lucia; Tomaiuolo, Francesco; Koch, Giacomo; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

    2014-10-01

    We report the neuropsychological and MRI investigation of a patient (GP) who developed a selective impairment of spatial short-term memory (STM) following damage to the dorso-mesial areas of the right frontal lobe. We assessed in this patient spatial STM with an experimental procedure that evaluated immediate and 5-20 s delayed recall of verbal, visual and spatial stimuli. The patient scored significantly worse than normal controls on tests that required delayed recall of spatial data. This could not be ascribed to a deficit of spatial episodic long-term memory because amnesic patients performed normally on these tests. Conversely, the patient scored in the normal range on tests of immediate recall of verbal, visual and spatial data and tests of delayed recall of verbal and visual data. Comparison with a previously described patient who had a selective deficit in immediate spatial recall and an ischemic lesion that affected frontal and parietal dorso-mesial areas in the right hemisphere (Carlesimo GA, Perri R, Turriziani P, Tomaiuolo F, Caltagirone C. Remembering what but not where: independence of spatial and visual working memory in the human brain. Cortex. 2001 Sep; 37(4):519-34) suggests that the right parietal areas are involved in the short-term storage of spatial information and that the dorso-mesial regions of the right frontal underlie mechanisms for the delayed maintenance of the same data.

  11. Detecting spatial memory deficits beyond blindness in tg2576 Alzheimer mice.

    Science.gov (United States)

    Yassine, Nour; Lazaris, Anelise; Dorner-Ciossek, Cornelia; Després, Olivier; Meyer, Laurence; Maitre, Michel; Mensah-Nyagan, Ayikoe Guy; Cassel, Jean-Christophe; Mathis, Chantal

    2013-03-01

    The retinal degeneration Pde6b(rd1) (rd) mutation can be a major pitfall in behavioral studies using tg2576 mice bred on a B6:SJL genetic background, 1 of the most widely used models of Alzheimer's disease. After a pilot study in wild type mice, performance of 8- and 16-month-old tg2576 mice were assessed in several behavioral tasks with the challenge of selecting 1 or more task(s) showing robust memory deficits on this genetic background. Water maze acquisition was impossible in rd homozygotes, whereas Y-maze alternation, object recognition, and olfactory discrimination were unaffected by both the transgene and the rd mutation. Spatial memory retention of 8- and 16-month-old tg2576 mice, however, was dramatically affected independently of the rd mutation when mice had to recognize a spatial configuration of objects or to perform the Barnes maze. Thus, the latter tasks appear extremely useful to evaluate spatial memory deficits and to test cognitive therapies in tg2576 mice and other mouse models bred on a background susceptible to visual impairment. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny.

    Science.gov (United States)

    Wimmer, M E; Briand, L A; Fant, B; Guercio, L A; Arreola, A C; Schmidt, H D; Sidoli, S; Han, Y; Garcia, B A; Pierce, R C

    2017-11-01

    Paternal environmental perturbations including exposure to drugs of abuse can produce profound effects on the physiology and behavior of offspring via epigenetic modifications. Here we show that adult drug-naive male offspring of cocaine-exposed sires have memory formation deficits and associated reductions in NMDA receptor-mediated hippocampal synaptic plasticity. Reduced levels of the endogenous NMDA receptor co-agonist d-serine were accompanied by increased expression of the d-serine degrading enzyme d-amino acid oxidase (Dao1) in the hippocampus of cocaine-sired male progeny. Increased Dao1 transcription was associated with enrichment of permissive epigenetic marks on histone proteins in the hippocampus of male cocaine-sired progeny, some of which were enhanced near the Dao1 locus. Finally, hippocampal administration of d-serine reversed both the memory formation and synaptic plasticity deficits. Collectively, these results demonstrate that paternal cocaine exposure produces epigenetic remodeling in the hippocampus leading to NMDA receptor-dependent memory formation and synaptic plasticity impairments only in male progeny, which has significant implications for the male descendants of chronic cocaine users.

  13. Comparative effect of Camellia sinensis teas on object recognition test deficit and metabolic changes induced by cafeteria diet.

    Science.gov (United States)

    Soares, Melina Bucco; Ramalho, Juliana Bernera; Izaguirry, Aryele Pinto; Pavin, Natasha Frasson; Spiazzi, Cristiano Chiapinotto; Schimidt, Helen Lidiane; Mello-Carpes, Pâmela Billig; Santos, Francielli Weber

    2017-12-27

    Consumption of high-fat and high-sugar diets in Western countries has increased significantly causing major global health problems including metabolic syndrome and obesity. In addition, studies have suggested that obesity can lead to learning and memory deficits. In this context, the use of natural compounds with low costs, minor side effects and increased antioxidant activity, such as teas, could reduce the damages induced by obesity. We investigated the effect of white, green, red, and black teas (Camellia sinensis) and their possible neuroprotective mechanisms in an experimental obesity model induced by a cafeteria diet (CD). Female Swiss mice (20-30 g) were used; they received a normal diet or a hypercaloric diet (CD) during 8 weeks. Concomitantly, some mice received orally white, green, red, or black teas (1% dose) or water. The mice subjected to CD showed weight gain, body fat accumulation, increased glucose, cholesterol, and triglycerides, associated to recognition memory deficits and increased reactive species (RS) levels and acetylcholinesterase (AChE) activity in the hippocampus. All teas significantly reduced AChE activity and partially reduced fat accumulation. Green and red teas reduced memory deficit. White, green, and black teas reduced RS levels, while only green and black tea reduced plasma triglyceride levels. According to the results obtained it is possible to conclude that green tea was better than other teas in reducing effects of the CD model, being able to protect a greater number of parameters.

  14. Retinoic acid restores adult hippocampal neurogenesis and reverses spatial memory deficit in vitamin a deprived rats

    OpenAIRE

    Bonnet, Emilie; Touyarot, katia; Alfos, Serge; Pallet, Véronique; Higueret, Paul; Abrous, Djoher Nora

    2008-01-01

    A dysfunction of retinoid hippocampal signaling pathway has been involved in the appearance of affective and cognitive disorders. However, the underlying neurobiological mechanisms remain unknown. Hippocampal granule neurons are generated throughout life and are involved in emotion and memory. Here, we investigated the effects of vitamin A deficiency (VAD) on neurogenesis and memory and the ability of retinoic acid (RA) treatment to prevent VAD-induced impairments. Adult retinoid-deficient ra...

  15. Supplementation with different teas from Camellia sinensis prevents memory deficits and hippocampus oxidative stress in ischemia-reperfusion.

    Science.gov (United States)

    Martins, Alexandre; Schimidt, Helen L; Garcia, Alexandre; Colletta Altermann, Caroline Dalla; Santos, Francielli W; Carpes, Felipe P; da Silva, Weber Cláudio; Mello-Carpes, Pâmela B

    2017-09-01

    Memory and cognition impairments resultant of ischemic stroke could be minimized or avoided by antioxidant supplementation. In this regard, the neuroprotective potential of Green tea from Camellia sinensis has been investigated. However, there is a lack of information regarding the neuroprotective potential of others teas processed from the Camellia sinensis. Here we investigate the neuroprotective role of green, red, white and black tea on memory deficits and brain oxidative stress in a model of ischemic stroke in rats. Our findings show that green and red teas prevent deficits in object and social recognition memories, but only green tea protects against deficits in spatial memory and avoids hippocampal oxidative status and intense necrosis and others alterations in the brain tissue. In summary, green tea shows better neuroprotection in ischemic stroke than the others teas from Camellia sinensis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Relationships between default-mode network connectivity, medial temporal lobe structure, and age-related memory deficits.

    Science.gov (United States)

    Ward, Andrew M; Mormino, Elizabeth C; Huijbers, Willem; Schultz, Aaron P; Hedden, Trey; Sperling, Reisa A

    2015-01-01

    Advanced aging negatively impacts memory performance. Brain aging has been associated with shrinkage in medial temporal lobe structures essential for memory--including hippocampus and entorhinal cortex--and with deficits in default-mode network connectivity. Yet, whether and how these imaging markers are relevant to age-related memory deficits remains a topic of debate. Using a sample of 182 older (age 74.6 ± 6.2 years) and 66 young (age 22.2 ± 3.6 years) participants, this study examined relationships among memory performance, hippocampus volume, entorhinal cortex thickness, and default-mode network connectivity across aging. All imaging markers and memory were significantly different between young and older groups. Each imaging marker significantly mediated the relationship between age and memory performance and collectively accounted for most of the variance in age-related memory performance. Within older participants, default-mode connectivity and hippocampus volume were independently associated with memory. Structural equation modeling of cross-sectional data within older participants suggest that entorhinal thinning may occur before reduced default-mode connectivity and hippocampal volume loss, which in turn lead to deficits in memory performance. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Shared etiology of phonological memory and vocabulary deficits in school-age children.

    Science.gov (United States)

    Peterson, Robin L; Pennington, Bruce F; Samuelsson, Stefan; Byrne, Brian; Olson, Richard K

    2013-08-01

    The goal of this study was to investigate the etiologic basis for the association between deficits in phonological memory (PM) and vocabulary in school-age children. Children with deficits in PM or vocabulary were identified within the International Longitudinal Twin Study (ILTS; Samuelsson et al., 2005). The ILTS includes 1,045 twin pairs (between the ages of 5 and 8 years) from the United States, Australia, and Scandinavia. The authors applied the DeFries-Fulker ( DeFries & Fulker, 1985, 1988) regression method to determine whether problems in PM and vocabulary tend to co-occur because of overlapping genes, overlapping environmental risk factors, or both. Among children with isolated PM deficits, the authors found significant bivariate heritability of PM and vocabulary weaknesses both within and across time. However, when probands were selected for a vocabulary deficit, there was no evidence for bivariate heritability. In this case, it appears that the PM-vocabulary relationship is caused by common shared environmental experiences. The findings are consistent with previous research on the heritability of specific language impairment and suggest that there are etiologic subgroups of children with low vocabulary for different reasons, 1 being more influenced by genes and another being more influenced by environment.

  18. Amsterdam Short-Term Memory test: a new procedure for the detection of feigned memory deficits

    NARCIS (Netherlands)

    Schagen, S.; Schmand, B.; de Sterke, S.; Lindeboom, J.

    1997-01-01

    The validity of two malingering tests, the newly developed Amsterdam Short-Term Memory (ASTM) test and the Distraction test (Baker, Hanley, Jackson, Kimmance, & Slade, 1993) was examined in a group of patients with closed-head injury (CHI), a normal control group, and a control group with

  19. Working Memory Deficits in Children with Reading Difficulties: Memory Span and Dual Task Coordination

    Science.gov (United States)

    Wang, Shinmin; Gathercole, Susan E.

    2013-01-01

    The current study investigated the cause of the reported problems in working memory in children with reading difficulties. Verbal and visuospatial simple and complex span tasks, and digit span and reaction times tasks performed singly and in combination, were administered to 46 children with single word reading difficulties and 45 typically…

  20. Nutritional deficits during early development affect hippocampal structure and spatial memory later in life.

    Science.gov (United States)

    Pravosudov, Vladimir V; Lavenex, Pierre; Omanska, Alicja

    2005-10-01

    Development rates vary among individuals, often as a result of direct competition for food. Survival of young might depend on their learning abilities, but it remains unclear whether learning abilities are affected by nutrition during development. The authors demonstrated that compared with controls, 1-year-old Western scrub jays (Aphelocoma californica) that experienced nutritional deficits during early posthatching development had smaller hippocampi with fewer neurons and performed worse in a cache recovery task and in a spatial version of an associative learning task. In contrast, performance of nutritionally deprived birds was similar to that of controls in 2 color versions of an associative learning task. These findings suggest that nutritional deficits during early development have long-term consequences for hippocampal structure and spatial memory, which, in turn, are likely to have a strong impact on animals' future fitness.

  1. Impaired encoding of rapid pitch information underlies perception and memory deficits in congenital amusia.

    Science.gov (United States)

    Albouy, Philippe; Cousineau, Marion; Caclin, Anne; Tillmann, Barbara; Peretz, Isabelle

    2016-01-06

    Recent theories suggest that the basis of neurodevelopmental auditory disorders such as dyslexia or specific language impairment might be a low-level sensory dysfunction. In the present study we test this hypothesis in congenital amusia, a neurodevelopmental disorder characterized by severe deficits in the processing of pitch-based material. We manipulated the temporal characteristics of auditory stimuli and investigated the influence of the time given to encode pitch information on participants' performance in discrimination and short-term memory. Our results show that amusics' performance in such tasks scales with the duration available to encode acoustic information. This suggests that in auditory neuro-developmental disorders, abnormalities in early steps of the auditory processing can underlie the high-level deficits (here musical disabilities). Observing that the slowing down of temporal dynamics improves amusics' pitch abilities allows considering this approach as a potential tool for remediation in developmental auditory disorders.

  2. The memory-enhancing effect of erucic acid on scopolamine-induced cognitive impairment in mice.

    Science.gov (United States)

    Kim, Eunji; Ko, Hae Ju; Jeon, Se Jin; Lee, Sunhee; Lee, Hyung Eun; Kim, Ha Neul; Woo, Eun-Rhan; Ryu, Jong Hoon

    2016-03-01

    Erucic acid is a monounsaturated omega-9 fatty acid isolated from the seed of Raphanus sativus L. that is known to normalize the accumulation of very long chain fatty acids in the brains of patients suffering from X-linked adrenoleukodystrophy. Here, we investigated whether erucic acid enhanced cognitive function or ameliorated scopolamine-induced memory impairment using the passive avoidance, Y-maze and Morris water maze tasks. Erucic acid (3mg/kg, p.o.) enhanced memory performance in normal naïve mice. In addition, erucic acid (3mg/kg, p.o.) ameliorated scopolamine-induced memory impairment, as assessed via the behavioral tasks. We then investigated the underlying mechanism of the memory-enhancing effect of erucic acid. The administration of erucic acid increased the phosphorylation levels of phosphatidylinositide 3-kinase (PI3K), protein kinase C zeta (PKCζ), extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB) and additional protein kinase B (Akt) in the hippocampus. These results suggest that erucic acid has an ameliorative effect in mice with scopolamine-induced memory deficits and that the effect of erucic acid is partially due to the activation of PI3K-PKCζ-ERK-CREB signaling as well as an increase in phosphorylated Akt in the hippocampus. Therefore, erucic acid may be a novel therapeutic agent for diseases associated with cognitive deficits, such as Alzheimer's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Tau reduction diminishes spatial learning and memory deficits after mild repetitive traumatic brain injury in mice.

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    Jason S Cheng

    Full Text Available OBJECTIVE: Because reduction of the microtubule-associated protein Tau has beneficial effects in mouse models of Alzheimer's disease and epilepsy, we wanted to determine whether this strategy can also improve the outcome of mild traumatic brain injury (TBI. METHODS: We adapted a mild frontal impact model of TBI for wildtype C57Bl/6J mice and characterized the behavioral deficits it causes in these animals. The Barnes maze, Y maze, contextual and cued fear conditioning, elevated plus maze, open field, balance beam, and forced swim test were used to assess different behavioral functions. Magnetic resonance imaging (MRI, 7 Tesla and histological analysis of brain sections were used to look for neuropathological alterations. We also compared the functional effects of this TBI model and of controlled cortical impact in mice with two, one or no Tau alleles. RESULTS: Repeated (2-hit, but not single (1-hit, mild frontal impact impaired spatial learning and memory in wildtype mice as determined by testing of mice in the Barnes maze one month after the injury. Locomotor activity, anxiety, depression and fear related behaviors did not differ between injured and sham-injured mice. MRI imaging did not reveal focal injury or mass lesions shortly after the injury. Complete ablation or partial reduction of tau prevented deficits in spatial learning and memory after repeated mild frontal impact. Complete tau ablation also showed a trend towards protection after a single controlled cortical impact. Complete or partial reduction of tau also reduced the level of axonopathy in the corpus callosum after repeated mild frontal impact. INTERPRETATION: Tau promotes or enables the development of learning and memory deficits and of axonopathy after mild TBI, and tau reduction counteracts these adverse effects.

  4. Oligonol improves memory and cognition under an amyloid β(25-35)-induced Alzheimer's mouse model.

    Science.gov (United States)

    Choi, Yoon Young; Maeda, Takahiro; Fujii, Hajime; Yokozawa, Takako; Kim, Hyun Young; Cho, Eun Ju; Shibamoto, Takayuki

    2014-07-01

    Alzheimer's disease is an age-dependent progressive neurodegenerative disorder that results in impairments of memory and cognitive function. It is hypothesized that oligonol has ameliorative effects on memory impairment and reduced cognitive functions in mice with Alzheimer's disease induced by amyloid β(25-35) (Aβ(25-35)) injection. The protective effect of an oligonol against Aβ(25-35)-induced memory impairment was investigated in an in vivo Alzheimer's mouse model. The aggregation of Aβ25-35 was induced by incubation at 37°C for 3 days before injection into mice brains (5 nmol/mouse), and then oligonol was orally administered at 100 and 200 mg/kg of body weight for 2 weeks. Memory and cognition were observed in T-maze, object recognition, and Morris water maze tests. The group injected with Aβ(25-35) showed impairments in both recognition and memory. However, novel object recognition and new route awareness abilities were dose dependently improved by the oral administration of oligonol. In addition, the results of the Morris water maze test indicated that oligonol exerted protective activity against cognitive impairment induced by Aβ(25-35). Furthermore, nitric oxide formation and lipid peroxidation were significantly elevated by Aβ(25-35), whereas oligonol treatment significantly decreased nitric oxide formation and lipid peroxidation in the brain, liver, and kidneys. The present results suggest that oligonol improves Aβ(25-35)-induced memory deficit and cognition impairment. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Component deficits of visual neglect: "Magnetic" attraction of attention vs. impaired spatial working memory.

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    Toba, Monica N; Rabuffetti, Marco; Duret, Christophe; Pradat-Diehl, Pascale; Gainotti, Guido; Bartolomeo, Paolo

    2018-01-31

    Visual neglect is a disabling consequence of right hemisphere damage, whereby patients fail to detect left-sided objects. Its precise mechanisms are debated, but there is some consensus that distinct component deficits may variously associate and interact in different patients. Here we used a touch-screen based procedure to study two putative component deficits of neglect, rightward "magnetic" attraction of attention and impaired spatial working memory, in a group of 47 right brain-damaged patients, of whom 33 had signs of left neglect. Patients performed a visual search task on three distinct conditions, whereby touched targets could (1) be tagged, (2) disappear or (3) show no change. Magnetic attraction of attention was defined as more left neglect on the tag condition than on the disappear condition, where right-sided disappeared targets could not capture patients' attention. Impaired spatial working memory should instead produce more neglect on the no change condition, where no external cue indicated that a target had already been explored, than on the tag condition. Using a specifically developed analysis algorithm, we identified significant differences of performance between the critical conditions. Neglect patients as a group performed better on the disappear condition than on the no change condition and also better in the tag condition comparing with the no change condition. No difference was found between the tag condition and the disappear condition. Some of our neglect patients had dissociated patterns of performance, with predominant magnetic attraction or impaired spatial working memory. Anatomical results issued from both grey matter analysis and fiber tracking were consistent with the typical patterns of fronto-parietal and occipito-frontal disconnection in neglect, but did not identify lesional patterns specifically associated with one or another deficit, thus suggesting the possible co-localization of attentional and working memory processes in

  6. Involvement of the endocannabinoid system in phencyclidine-induced cognitive deficits modelling schizophrenia.

    Science.gov (United States)

    Vigano, Daniela; Guidali, Cinzia; Petrosino, Stefania; Realini, Natalia; Rubino, Tiziana; Di Marzo, Vincenzo; Parolaro, Daniela

    2009-06-01

    Recent advances in the neurobiology of cannabinoids have renewed interest in the association between cannabis and schizophrenia. Our studies showed that chronic-intermittent phencyclidine (PCP) treatment of rats, an animal model of schizophrenia-like cognitive deficit, impaired recognition memory in the novel object recognition (NOR) test and induced alterations in CB1 receptor functionality and in endocannabinoid levels mainly in the prefrontal cortex. In this region, we observed a significant reduction in GTPgammaS binding (-41%) accompanied by an increase in the levels of the endocannabinoid 2-AG (+38%) in PCP-treated rats, suggesting that a maladaptation of the endocannabinoid system might contribute to the glutamatergic-related cognitive symptoms encountered in schizophrenia disorders. Moreover, we evaluated the ability of the main psychoactive ingredient of marijuana, Delta9-tetrahydrocannabinol (THC), to modulate the cognitive dysfunctions and neuroadaptations in the endocannabinoid system induced by PCP. Chronic THC co-treatment worsened PCP-induced cognitive impairment, without inducing any effect per se, and in parallel, it provoked a severe reduction in the levels of the other endocannabinoid, AEA, vs. either vehicle (-73%) or PCP (-64%), whereas it reversed the PCP-induced increase in 2-AG levels. These results point to the involvement of the endocannabinoid system in this pharmacological model of cognitive dysfunction, with a potentially different role of AEA and 2-AG in schizophrenia-like behaviours and suggest that prolonged cannabis use might aggravate cognitive performances induced by chronic PCP by throwing off-balance the endocannabinoid system.

  7. Visuo-spatial memory deficits following medial temporal lobe damage: A comparison of three patient groups.

    Science.gov (United States)

    Esfahani-Bayerl, Nazli; Finke, Carsten; Braun, Mischa; Düzel, Emrah; Heekeren, Hauke R; Holtkamp, Martin; Hasper, Dietrich; Storm, Christian; Ploner, Christoph J

    2016-01-29

    The contributions of the hippocampal formation and adjacent regions of the medial temporal lobe (MTL) to memory are still a matter of debate. It is currently unclear, to what extent discrepancies between previous human lesion studies may have been caused by the choice of distinct patient models of MTL dysfunction, as disorders affecting this region differ in selectivity, laterality and mechanisms of post-lesional compensation. Here, we investigated the performance of three distinct patient groups with lesions to the MTL with a battery of visuo-spatial short-term memory tasks. Thirty-one subjects with either unilateral damage to the MTL (postsurgical lesions following resection of a benign brain tumor, 6 right-sided lesions, 5 left) or bilateral damage (10 post-encephalitic lesions, 10 post-anoxic lesions) performed a series of tasks requiring short-term memory of colors, locations or color-location associations. We have shown previously that performance in the association task critically depends on hippocampal integrity. Patients with postsurgical damage of the MTL showed deficient performance in the association task, but performed normally in color and location tasks. Patients with left-sided lesions were almost as impaired as patients with right-sided lesions. Patients with bilateral post-encephalitic lesions showed comparable damage to MTL sub-regions and performed similarly to patients with postsurgical lesions in the association task. However, post-encephalitic patients showed additional impairments in the non-associative color and location tasks. A strikingly similar pattern of deficits was observed in post-anoxic patients. These results suggest a distinct cerebral organization of associative and non-associative short-term memory that was differentially affected in the three patient groups. Thus, while all patient groups may provide appropriate models of medial temporal lobe dysfunction in associative visuo-spatial short-term memory, additional deficits in

  8. Sleep promotes consolidation of emotional memory in healthy children but not in children with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Prehn-Kristensen, Alexander; Munz, Manuel; Molzow, Ina; Wilhelm, Ines; Wiesner, Christian D; Baving, Lioba

    2013-01-01

    Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD) is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline) and delayed (target) retrieval session. The emotional memory bias was baseline-corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake). We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta) during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD.

  9. Sleep promotes consolidation of emotional memory in healthy children but not in children with attention-deficit hyperactivity disorder.

    Directory of Open Access Journals (Sweden)

    Alexander Prehn-Kristensen

    Full Text Available Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline and delayed (target retrieval session. The emotional memory bias was baseline-corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake. We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD.

  10. Adaptive Plasticity in the Hippocampus of Young Mice Intermittently Exposed to MDMA Could Be the Origin of Memory Deficits.

    Science.gov (United States)

    Abad, S; Camarasa, J; Pubill, D; Camins, A; Escubedo, E

    2016-12-01

    (±)3,4-Methylenedioxymethamphetamine (MDMA) is a relatively selective dopaminergic neurotoxin in mice. This study was designed to evaluate whether MDMA exposure affects their recognition memory and hippocampal expression of plasticity markers. Mice were administered with increasing doses of MDMA once per week for 8 weeks (three times in 1 day, every 3 h) and killed 2 weeks (2w) or 3 months (3m) later. The treatment did not modify hippocampal tryptophan hydroxylase 2, a serotonergic indicator, but induced an initial reduction in dopaminergic markers in substantia nigra, which remained stable for at least 3 months. In parallel, MDMA produced a decrease in dopamine (DA) levels in the striatum at 2w, which were restored 3 months later, suggesting dopaminergic terminal regeneration (sprouting phenomenon). Moreover, recognition memory was assessed using the object recognition test. Young (2w) and mature (3m) adult mice exhibited impaired memory after 24-h but not after just 1-h retention interval. Two weeks after the treatment, animals showed constant levels of CREB but an increase in its phosphorylated form and in c-Fos expression. Brain-derived neurotrophic factor (BDNF) and especially Arc overexpression was sustained and long-lasting. We cannot rule out the absence of MDMA injury in the hippocampus being due to the generation of BDNF. The levels of NMDAR2B, PSD-95, and synaptophysin were unaffected. In conclusion, the young mice exposed to MDMA showed increased expression of early key markers of plasticity, which sometimes remained for 3 months, and suggests hippocampal maladaptive plasticity that could explain memory deficits evidenced here.

  11. The effect of genistein on intracerebroventricular streptozotocin-induced cognitive deficits in male rat

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    Tourandokht Balouchnejadmojarad

    2009-01-01

    Full Text Available Abstract  Introduction: Intracerebroventricular (ICV injection of streptozotocin (STZ causes cognitive impairment in rats. The beneficial effect of genistein (GEN was investigated on ICV STZ-induced learning, memory, and cognitive impairment in male rats. Methods: For this purpose, rats were injected with ICV STZ bilaterally, on days 1 and 3 (3 mg/kg. The STZ-injected rats received GEN (1 mg/kg/day, p.o. starting one day pre-surgery for two weeks. The learning and memory performance was assessed using passive avoidance paradigm, and for spatial cognition evaluation, radial eight-arm maze (RAM task was used.  Results: It was found out that GEN-treated STZ-injected rats show higher correct choices and lower errors in RAM than vehicle-treated STZ-injected rats. In addition, GEN administration significantly attenuated learning and memory impairment in treated STZ-injected group in passive avoidance test.Discussion: These results demonstrate the effectiveness of GEN in preventing the cognitive deficits caused by ICV STZ in rats and its potential in the treatment of neurodegenerative diseases such as Alzheimer's disease (AD.

  12. The effect of genistein on intracerebroventricular streptozotocin-induced cognitive deficits in male rat

    Directory of Open Access Journals (Sweden)

    Tourandokht Balouchnejadmojarad

    2009-01-01

    Full Text Available   Abstract  Introduction: Intracerebroventricular (ICV injection of streptozotocin (STZ causes cognitive impairment in rats. The beneficial effect of genistein (GEN was investigated on ICV STZ-induced learning, memory, and cognitive impairment in male rats. Methods: For this purpose, rats were injected with ICV STZ bilaterally, on days 1 and 3 (3 mg/kg. The STZ-injected rats received GEN (1 mg/kg/day, p.o. starting one day pre-surgery for two weeks. The learning and memory performance was assessed using passive avoidance paradigm, and for spatial cognition evaluation, radial eight-arm maze (RAM task was used.  Results: It was found out that GEN-treated STZ-injected rats show higher correct choices and lower errors in RAM than vehicle-treated STZ-injected rats. In addition, GEN administration significantly attenuated learning and memory impairment in treated STZ-injected group in passive avoidance test.Discussion: These results demonstrate the effectiveness of GEN in preventing the cognitive deficits caused by ICV STZ in rats and its potential in the treatment of neurodegenerative diseases such as Alzheimer's disease (AD.  

  13. Memory Deficit is Associated with Worse Functional Trajectories Among Older Adults in Low Vision Rehabilitation for Macular Disease

    Science.gov (United States)

    Whitson, Heather E.; Whitaker, Diane; Sanders, Linda L.; Potter, Guy G.; Cousins, Scott W.; Ansah, Deidra; McConnell, Eleanor; Pieper, Carl F.; Landerman, Lawrence; Steffens, David C.; Cohen, Harvey J.

    2012-01-01

    Objectives Older adults with macular disease are at increased risk of memory decline and incident dementia. Low vision rehabilitation (LVR) aims to preserve independence in people with irreversible vision loss, but comorbid memory problems could limit the success of rehabilitation. This study examined whether performance on a brief memory test is related to functional outcomes among older patients undergoing LVR for macular disease. Design Observational cohort study of patients receiving outpatient LVR Setting Academic center Participants 91 seniors (average age 80.1 years) with macular disease Measurements Memory was assessed at baseline with a 10-word list; memory deficit was defined as immediate recall of ≤ two words. Vision-related function was measured with the 25-item Visual Function Questionnaire (VFQ-25)administered at baseline and during subsequent interviews (mean length of follow up = 115 days). Linear mixed models (LMMs) were constructed to compare average trajectories of four VFQ-25 subscales: near activities, distance activities, dependency, and role difficulty. Results The 29.7% of patients with memory deficit tended to decline in ability to accomplish activities that involve near vision. Controlling for age, sex, and education, the functional trajectory of participants with memory deficit differed significantly from that of participants with better memory (p=0.002), who tended to report improvements in ability to accomplish near activities. Conclusion Among older adults receiving LVR for macular disease, those with memory deficit experienced worse functional trajectories in their ability to perform specific visually mediated tasks. A brief memory screen may help explain variability in rehabilitation outcomes and identify patients who might require special accommodations. PMID:23126548

  14. Enriched environment ameliorates depression-induced cognitive deficits and restores abnormal hippocampal synaptic plasticity.

    Science.gov (United States)

    Mahati, K; Bhagya, V; Christofer, T; Sneha, A; Shankaranarayana Rao, B S

    2016-10-01

    Severe depression compromises structural and functional integrity of the brain and results in impaired learning and memory, maladaptive synaptic plasticity as well as degenerative changes in the hippocampus and amygdala. The precise mechanisms underlying cognitive dysfunctions in depression remain largely unknown. On the other hand, enriched environment (EE) offers beneficial effects on cognitive functions, synaptic plasticity in the hippocampus. However, the effect of EE on endogenous depression associated cognitive dysfunction has not been explored. Accordingly, we have attempted to address this issue by investigating behavioural, structural and synaptic plasticity mechanisms in an animal model of endogenous depression after exposure to enriched environment. Our results demonstrate that depression is associated with impaired spatial learning and enhanced anxiety-like behaviour which is correlated with hypotrophy of the dentate gyrus and amygdalar hypertrophy. We also observed a gross reduction in the hippocampal long-term potentiation (LTP). We report a complete behavioural recovery with reduced indices of anhedonia and behavioural despair, reduced anxiety-like behaviour and improved spatial learning along with a complete restoration of dentate gyrus and amygdalar volumes in depressive rats subjected to EE. Enrichment also facilitated CA3-Schaffer collateral LTP. Our study convincingly proves that depression-induces learning deficits and impairs hippocampal synaptic plasticity. It also highlights the role of environmental stimuli in restoring depression-induced cognitive deficits which might prove vital in outlining more effective strategies to treat major depressive disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Phosphodiesterase-4 inhibitors ameliorates cognitive deficits in deoxycorticosterone acetate induced hypertensive rats via cAMP/CREB signaling system.

    Science.gov (United States)

    Jabaris, S Sugin Lal; Sumathy, Haridass; Girish, Ramesh; Narayanan, Shridhar; Sugumar, Mani; Saravana Babu, Chidambaram; Thanikachalam, Sadagopan; Thanikachalam, Mohan

    2015-10-05

    Phosphodiesterase-4 (PDE-4) inhibitors promote memory by blocking the degradation of cAMP. Existing evidence also shows that neuronal survival and plasticity are dependent on the phosphorylation of cAMP-response element-binding protein. In this regard, PDE-4 inhibitors have also been shown to reverse pharmacologically and genetically induced memory impairment in animal models. In the present study, the authors examined the effect of both rolipram and roflumilast (PDE-4 inhibitors) on the impairment of learning and memory observed in hypertensive rats. Deoxycorticosterone acetate (DOCA) salt hypertensive model was used to induce learning and memory deficits. The mRNA expression of different PDE-4 subtypes along with the protein levels of pCREB and BDNF in the hippocampus was quantified. Systolic blood pressure was significantly increased in DOCA salt hypertensive rats when compared to sham operated rats. This effect was reversed by clonidine, an α2 receptor agonist, while PDE-4 inhibitors did not. PDE-4 inhibitors significantly improved the time-induced memory deficits in object recognition task (ORT). In DOCA salt hypertensive rats, the gene expression of PDE-4B and PDE-4D was significantly increased. Furthermore, both pCREB and BDNF showed decreased levels of expression in hypertensive rats in comparison to sham operated rats. Repeated administration of PDE-4 inhibitors significantly decreased both PDE-4B and PDE-4D with an increase in the expression of pCREB and BDNF in hypersensitive rats. Also, rolipram, roflumilast and roflumilast N-oxide showed a linear increase in the plasma and brain concentrations after ORT. Our present findings suggested that PDE-4 inhibitors ameliorate hypertension-induced learning impairment via cAMP/CREB signaling that regulates BDNF expression downstream in the rat hippocampus. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Anatomical Modularity of Verbal Working Memory? Functional Anatomical Evidence from a Famous Patient with Short-Term Memory Deficits

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    Eraldo Paulesu

    2017-05-01

    Full Text Available Cognitive skills are the emergent property of distributed neural networks. The distributed nature of these networks does not necessarily imply a lack of specialization of the individual brain structures involved. However, it remains questionable whether discrete aspects of high-level behavior might be the result of localized brain activity of individual nodes within such networks. The phonological loop of working memory, with its simplicity, seems ideally suited for testing this possibility. Central to the development of the phonological loop model has been the description of patients with focal lesions and specific deficits. As much as the detailed description of their behavior has served to refine the phonological loop model, a classical anatomoclinical correlation approach with such cases falls short in telling whether the observed behavior is based on the functions of a neural system resembling that seen in normal subjects challenged with phonological loop tasks or whether different systems have taken over. This is a crucial issue for the cross correlation of normal cognition, normal physiology, and cognitive neuropsychology. Here we describe the functional anatomical patterns of JB, a historical patient originally described by Warrington et al. (1971, a patient with a left temporo-parietal lesion and selective short phonological store deficit. JB was studied with the H215O PET activation technique during a rhyming task, which primarily depends on the rehearsal system of the phonological loop. No residual function was observed in the left temporo-parietal junction, a region previously associated with the phonological buffer of working memory. However, Broca's area, the major counterpart of the rehearsal system, was the major site of activation during the rhyming task. Specific and autonomous activation of Broca's area in the absence of afferent inputs from the other major anatomical component of the phonological loop shows that a certain

  17. Working Memory Deficits Predict Short-term Smoking Resumption Following Brief Abstinence*

    Science.gov (United States)

    Patterson, Freda; Jepson, Christopher; Loughead, James; Perkins, Kenneth; Strasser, Andrew A.; Siegel, Steven; Frey, Joseph; Gur, Ruben; Lerman, Caryn

    2009-01-01

    As many as one-half of smokers relapse in the first week following a quit attempt, and subjective reports of cognitive deficits in early abstinence are associated with increased relapse risk. This study examined whether objective cognitive performance after three days of abstinence predicts smoking resumption in a 7-day simulated quit attempt. Sixty-seven treatment-seeking smokers received either varenicline or placebo (randomized double-blind) for 21 days. Following medication run-up (days 1-10), there was a 3-day mandatory (biochemically confirmed) abstinence period (days 11-13) during which working memory (Letter-N-Back Task) and sustained attention (Continuous Performance Task) were assessed (day 13). Participants were then exposed to a scheduled smoking lapse and instructed to try to remain abstinent for the next 7 days (days 15-21). Poorer cognitive performance (slower correct reaction time on Letter-N-Back task) during abstinence predicted more rapid smoking resumption among those receiving placebo (p=.038) but not among those receiving varenicline. These data lend further support for the growing recognition that cognitive deficits involving working memory are a core symptom of nicotine withdrawal and a potential target for the development of pharmacological and behavioral treatments. PMID:19733449

  18. Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model.

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    Hüttenrauch, M; Brauß, A; Kurdakova, A; Borgers, H; Klinker, F; Liebetanz, D; Salinas-Riester, G; Wiltfang, J; Klafki, H W; Wirths, O

    2016-05-03

    The evidence for a protective role of physical activity on the risk and progression of Alzheimer's disease (AD) has been growing in the last years. Here we studied the influence of a prolonged physical and cognitive stimulation on neurodegeneration, with special emphasis on hippocampal neuron loss and associated behavioral impairment in the Tg4-42 mouse model of AD. Tg4-42 mice overexpress Aβ4-42 without any mutations, and develop an age-dependent hippocampal neuron loss associated with a severe memory decline. We demonstrate that long-term voluntary exercise diminishes CA1 neuron loss and completely rescues spatial memory deficits in different experimental settings. This was accompanied by changes in the gene expression profile of Tg4-42 mice. Deep sequencing analysis revealed an upregulation of chaperones involved in endoplasmatic reticulum protein processing, which might be intimately linked to the beneficial effects seen upon long-term exercise. We believe that we provide evidence for the first time that enhanced physical activity counteracts neuron loss and behavioral deficits in a transgenic AD mouse model. The present findings underscore the relevance of increased physical activity as a potential strategy in the prevention of dementia.

  19. The impact of level of education on age-related deficits in associative memory: Behavioral and neuropsychological perspectives.

    Science.gov (United States)

    Peterson, Dwight J; Gargya, Sanchita; Kopeikin, Ksenia S; Naveh-Benjamin, Moshe

    2017-06-01

    Older adults have difficulty forming associations and binding distinct item components despite mostly preserved item memory potentially because they rely on more automatic, rather than strategic, processing when attempting to form, store, and retrieve associations from memory. An intriguing possibility is that older adults with greater access to strategic processes (e.g., those with a high level of education) may be less susceptible to age-related associative memory deficits. Two experiments assessed the degree to which a high level of education provides an effective dose of cognitive reserve (CR), potentially preserving associative memory. Standard younger and older adults' item and associative memory performance was compared to older adults who had attained a high level of education (mostly doctoral degrees). In both experiments (Experiment 1: person-action pairs; Experiment 2: unrelated word pairs), consistent evidence was found that older adults, regardless of the level of education, exhibited an age-related associative memory deficit relative to younger adults. Interestingly, neuropsychological assessment of both older adult groups revealed greater frontal lobe, but not enhanced medial temporal lobe, functioning in the highly educated. As such, although the highly educated older adults exhibited greater frontal lobe functioning than the standard older adults, this did not aid in the reduction of the age-related associative memory deficit. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Age-related top-down suppression deficit in the early stages of cortical visual memory processing

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    Gazzaley, Adam; Clapp, Wesley; Kelley, Jon; McEvoy, Kevin; Knight, Robert T.; D'Esposito, Mark

    2008-01-01

    In this study, electroencephalography (EEG) was used to examine the relationship between two leading hypotheses of cognitive aging, the inhibitory deficit and the processing speed hypothesis. We show that older adults exhibit a selective deficit in suppressing task-irrelevant information during visual working memory encoding, but only in the early stages of visual processing. Thus, the employment of suppressive mechanisms are not abolished with aging but rather delayed in time, revealing a de...

  1. Red peppers with moderate and severe pungency prevent the memory deficit and hepatic insulin resistance in diabetic rats with Alzheimer's disease.

    Science.gov (United States)

    Yang, Hye Jeong; Kwon, Dae Young; Kim, Min Jung; Kang, Suna; Moon, Na Rang; Daily, James W; Park, Sunmin

    2015-01-01

    Dementia induced by β-amyloid accumulation impairs peripheral glucose homeostasis, but red pepper extract improves glucose homeostasis. We therefore evaluated whether long-term oral consumption of different red pepper extracts improves cognitive dysfunction and glucose homeostasis in type 2 diabetic rats with β-amyloid-induced dementia. Male diabetic rats received hippocampal CA1 infusions of β-amyloid (25-35) (AD) or β-amyloid (35-25, non-plaque forming), at a rate of 3.6 nmol/day for 14 days (Non-AD). AD rats were divided into four dietary groups receiving either 1% lyophilized 70% ethanol extracts of either low, moderate and severe pungency red peppers (AD-LP, AD-MP, and AD-SP) or 1% dextrin (AD-CON) in Western diets (43% energy as fat). The ascending order of control memory deficit measured by passive avoidance test and water maze test. Furthermore, the accumulation of β-amyloid induced glucose intolerance, although serum insulin levels were elevated during the late phase of oral glucose tolerance test (OGTT). All of the red pepper extracts prevented the glucose intolerance in AD rats. Consistent with OGTT results, during euglycemic hyperinulinemic clamp glucose infusion rates were lower in AD-CON than Non-AD-CON with no difference in whole body glucose uptake. Hepatic glucose output at the hyperinsulinemic state was increased in AD-CON. β-amyloid accumulation exacerbated hepatic insulin resistance, but all red pepper extract treatments reversed the insulin resistance in AD rats. The extracts of moderate and severe red peppers were found to prevent the memory deficit and exacerbation of insulin resistance by blocking tau phosphorylation and β-amyloid accumulation in diabetic rats with experimentally induced Alzheimer's-like dementia. These results suggest that red pepper consumption might be an effective intervention for preventing age-related memory deficit.

  2. Comparing Iconic Memory in Children with and without Attention Deficit Hyperactivity Disorder

    Directory of Open Access Journals (Sweden)

    Nastaran Ahmadi

    2013-09-01

    Full Text Available Objective: Children with attention deficit hyperactivity disorder (ADHD do not process most information due to inattention and loss of the opportunity to save and retrieve information. Therefore, these children experience memory impairment. Although visual memory has been previously studied in children with ADHD, iconic memory in these children has been less evaluated. We aimed to study the possibility of iconic memory impairment in children with ADHD, and compare the results with that of children without ADHD.Methods: The experimental group of this study were 6-9 year-old children who referred to the Imam Hosein Clinic and were diagnosed as having ADHD by a psychiatrist during 2011-2012 (n=30.The subjects were interviewed clinically by a psychologist; and in order to diagnose ADHD, their parents and teachers were asked to complete the child symptom inventory-4 (CSI-4. The comparison group were 6-9 year-old children without ADHD who studied in 1st and 2nd educational district of Yazd (n=30. Subjects’ iconic memory was assessed using an iconic memory task. Repeated measure ANOVA was used for data analysis. Results:Based on the iconic memory test, the mean score of ADHD children was significantly lower than that of children without ADHD (P˂0.001. Moreover, the performance of the experimental group differed significantly when the duration of the presentation differed from 50 ms to 100 ms as compared to the control group (P˂0.001. The number of correct answers increased in the experimental group as the duration of presentation increased. However, children with ADHD scored less than children without ADHD at 50 ms as well as 100 ms. The means of ADHD children increased as the duration of the presentation increased from 50 ms to 100 ms to 300 ms (P<0.001.Conclusion:Visual memory is weaker in children with ADHD, and they have weaker performance than normal children in both visual and auditory symbols at presentation durations of 50 and 100 ms. The

  3. Memory outcomes following cognitive interventions in children with neurological deficits: A review with a focus on under-studied populations.

    Science.gov (United States)

    Schaffer, Yael; Geva, Ronny

    2016-01-01

    Given the primary role of memory in children's learning and well-being, the aim of this review was to examine the outcomes of memory remediation interventions in children with neurological deficits as a function of the affected memory system and intervention method. Fifty-seven studies that evaluated the outcome of memory interventions in children were identified. Thirty-four studies met the inclusion criteria, and were included in a systematic review. Diverse rehabilitation methods for improving explicit and implicit memory in children were reviewed. The analysis indicates that teaching restoration strategies may improve, and result in the generalisation of, semantic memory and working memory performance in children older than 7 years with mild to moderate memory deficits. Factors such as longer protocols, emotional support, and personal feedback contribute to intervention efficacy. In addition, the use of compensation aids seems to be highly effective in prospective memory tasks. Finally, the review unveiled a lack of studies with young children and the absence of group interventions. These findings point to the importance of future evidence-based intervention protocols in these areas.

  4. Worsening of memory deficit induced by energy-dense diet in a rat model of early-Alzheimer's disease is associated to neurotoxic Aβ species and independent of neuroinflammation.

    Science.gov (United States)

    Martino Adami, Pamela V; Galeano, Pablo; Wallinger, Marina L; Quijano, Celia; Rabossi, Alejandro; Pagano, Eleonora S; Olivar, Natividad; Reyes Toso, Carlos; Cardinali, Daniel; Brusco, Luis I; Do Carmo, Sonia; Radi, Rafael; Gevorkian, Goar; Castaño, Eduardo M; Cuello, A Claudio; Morelli, Laura

    2017-03-01

    Diet is a modifiable risk factor for Alzheimer's disease (AD), but the mechanisms linking alterations in peripheral metabolism and cognition remain unclear. Since it is especially difficult to study long-term effects of high-energy diet in individuals at risk for AD, we addressed this question by using the McGill-R-Thy1-APP transgenic rat model (Tg(+/-)) that mimics presymptomatic AD. Wild-type and Tg(+/-) rats were exposed during 6months to a standard diet or a Western diet (WD), high in saturated fat and sugar. Results from peripheral and hippocampal biochemical analysis and in situ respirometry showed that WD induced a metabolic syndrome and decreased presynaptic bioenergetic parameters without alterations in hippocampal insulin signaling or lipid composition. Cognitive tests, ELISA multiplex, Western blot, immunohistochemistry and RT-qPCR indicated that WD worsened cognition in Tg(+/-) rats, increased hippocampal levels of monomeric Aβ isoforms and oligomeric species, promoted deposits of N-Terminal pyroglutamate-Aβ (AβN3(pE)) in CA1 pyramidal neurons and interneurons, decreased transcript levels of genes involved in neuroprotective pathways such as Sirtuin-1 and increased nitrated proteins. Our results support the concept that in the presence of early Aβ pathology, diet-induced metabolic dysfunctions may contribute as a "second hit" to impair cognition. Noteworthy, such effect is not mediated by higher microglia activation or disruption of blood brain barrier. However, it may be attributed to increased amyloidogenic processing of amyloid precursor protein, generation of AβN3(pE) and dysregulation of pathways governed by Sirtuin-1. This evidence reinforces the implementation of prophylactic interventions in individuals at risk for AD. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Visuospatial working memory assessment using a digital tablet in adolescents with attention deficit hyperactivity disorder.

    Science.gov (United States)

    Hyun, Gi Jung; Park, Jin Wan; Kim, Jin Hee; Min, Kyoung Joon; Lee, Young Sik; Kim, Sun Mi; Han, Doug Hyun

    2018-04-01

    Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder hypothesized to involve impaired visuospatial working memory (VSWM). However, there are few studies utilizing neuropsychological tests to measure VSWM in ADHD adolescents. The Rey-Osterrieth complex figure test (ROCF) is commonly used as a neuropsychological test to assess visuospatial working memory for individuals with ADHD. We assessed working memory using the ROCF test on a digital Galaxy tablet with the technically new Gaussian filter method. Thirty adolescents with ADHD and 30 healthy control adolescents were recruited for participation in the current study. All adolescents were assessed with K-WISC-IV, Children's depression inventory, and the Korean ADHD rating scale. All adolescents were asked to copy the ROCF from paper onto a Galaxy tablet screen using a wireless pen. There was a significant difference in representative value of the deviation of the original images from template images (R-value) in copy and delayed recall between ADHD adolescents and healthy adolescents. There was no significant difference in R-value of immediate recall between ADHD adolescents and healthy adolescents. In all adolescents (ADHD and healthy) and ADHD adolescents, the R-value of copy was negatively correlated with visuospatial index and working memory index, and the R-value of delayed recall was negatively correlated with WMI. The R-value of copy and delayed recall was positively correlated with K-ARS in all adolescents and ADHD adolescents. ADHD adolescents showed differences in the R-values of copy and delayed recall in the digital ROCF version compared to healthy adolescents. The digital ROCF assessment tool can represent different patterns of visuospatial working memory abilities in ADHD adolescents compared to healthy adolescents. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Spatial memory deficits in a virtual reality eight-arm radial maze in schizophrenia.

    Science.gov (United States)

    Spieker, Elena A; Astur, Robert S; West, Jeffrey T; Griego, Jacqueline A; Rowland, Laura M

    2012-03-01

    Learning and memory impairments are present in schizophrenia (SZ) throughout the illness course and predict psychosocial function. Abnormalities in prefrontal and hippocampal function are thought to contribute to SZ deficits. The radial arm maze (RAM) is a test of spatial learning and memory in rodents that relies on intact prefrontal and hippocampal function. The goal of the present study was to investigate spatial learning in SZ using a virtual RAM. Thirty-three subjects with SZ and thirty-nine healthy controls (HC) performed ten trials of a virtual RAM task. Subjects attempted to learn to retrieve four rewards each located in separate arms. As expected, subjects with SZ used more time and traveled more distance to retrieve rewards, made more reference (RM) and working memory (WM) errors, and retrieved fewer rewards than HC. It is important to note that the SZ group did learn but did not reach the level of HC. Whereas RM errors decreased across trials in the SZ group, WM errors did not. There were no significant relationships between psychiatric symptom severity and maze performance. To our knowledge, use of a virtual 8-arm radial maze task in SZ to assess spatial learning is novel. Impaired virtual RAM performance in SZ is consistent with studies that examined RAM performance in animal models of SZ. Results provide further support for compromised prefrontal and hippocampal function underlying WM and RM deficits in SZ. The virtual RAM task could help bridge preclinical and clinical research for testing novel drug treatments of SZ. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Relationship between denial of memory deficit and dementia severity in Alzheimer disease.

    Science.gov (United States)

    Sevush, S

    1999-04-01

    To assess the relationship between denial of memory deficit and dementia severity in patients with Alzheimer disease (AD). Additionally, to introduce a new instrument, the Awareness of Memory Impairment Scale (AMIS), devised to minimize biases present in previous studies, especially those attributable to the use of difference scores and clinical ratings. Estimates of the magnitude of denial in patients with AD, and of its relationship with disease progression, have varied across studies. Part of this variability may have resulted from differences in the way investigators measured denial. In this study, the AMIS was used to obtain a relatively unbiased assessment of the relationship between denial and disease severity in patients with AD. Two hundred three patients with AD were studied, 106 longitudinally, and 40 age-matched control subjects were evaluated. Multiple regression analysis, controlled for age, sex, education, and duration of illness, was used to compare AMIS scores with disease severity cross-sectionally and to determine whether AMIS scores change over time. A similar analysis was performed using difference scores and clinical ratings to determine whether introduction of a new assessment instrument was warranted. Cross-sectionally, a small but statistically significant correlation between AD denial and dementia severity was found. Upon direct longitudinal assessment, no change in denial was noted after a mean interval of 1 year and 3 months. As expected, use of difference scores and clinical ratings yielded inflated correlations relative to those obtained with the AMIS. Denial of memory deficit correlates minimally with dementia severity in cross-sectional analysis but is independent of disease progression when assessed longitudinally.

  8. The Effect of Humanin on Spatial Memory Disorder Induced by Intraventricular Injection of Streptozotocin in Rats

    Directory of Open Access Journals (Sweden)

    2014-10-01

    Full Text Available Backgrounds & aim: Sporadic Alzheimer's is known as a new type of devastating disease that the impairment of the insulin signaling pathway may be one of factors causing it. The aim of study was to determine the impact of humanin on spatial memory impairment induced by intraventricular injection of streptozotocin in rats. Methods: In this experimental study 42 male rats weighing 250 to 300 g were selected and then cannule implanted bilaterally into their lateral ventricles. STZ or saline was injected in lateral ventricle every other day for the first and the third days. Humanin drug was injected at doses (0.01, 0.05, 0.1and 1 n/mol from days four until fourteenth. From day 14th to 17th the animal spatial memory was studied using water maze method. Data were analyzed by repeated measure and one-way analysis of variance (ANOVA followed by Tukey's test. Results: Groups treated with humanin at doses 0.01, 0.05, 0.1 and 1 n/mol could not significant improved spatial memory deficits induced by STZ. Conclusion: Humanin with its known neuroprotective effects could not improve spatial memory deficits induced by intra-cerebroventricular STZ.

  9. The Effects of Loranthus parasiticus on Scopolamine-Induced Memory Impairment in Mice.

    Science.gov (United States)

    Weon, Jin Bae; Lee, Jiwoo; Eom, Min Rye; Jung, Youn Sik; Ma, Choong Je

    2014-01-01

    This study is undertaken to evaluate cognitive enhancing effect and neuroprotective effect of Loranthus parasiticus. Cognitive enhancing effect of Loranthus parasiticus was investigated on scopolamine-induced amnesia model in Morris water maze test and passive avoidance test. We also examined the neuroprotective effect on glutamate-induced cell death in HT22 cells by MTT assay. These results of Morris water maze test and passive avoidance test indicated that 10 and 50 mg/kg of Loranthus parasiticus reversed scopolamine-induced memory deficits. Loranthus parasiticus also protected against glutamate-induced cytotoxicity in HT22 cells. As a result of in vitro test for elucidating possible mechanism, Loranthus parasiticus inhibited AChE activity, ROS production, and Ca(2+) accumulation. Loranthus parasiticus showed memory enhancing effect and neuroprotective effect and these effects may be related to inhibition of AChE activity, ROS level, and Ca(2+) influx.

  10. The Effects of Loranthus parasiticus on Scopolamine-Induced Memory Impairment in Mice

    Directory of Open Access Journals (Sweden)

    Jin Bae Weon

    2014-01-01

    Full Text Available This study is undertaken to evaluate cognitive enhancing effect and neuroprotective effect of Loranthus parasiticus. Cognitive enhancing effect of Loranthus parasiticus was investigated on scopolamine-induced amnesia model in Morris water maze test and passive avoidance test. We also examined the neuroprotective effect on glutamate-induced cell death in HT22 cells by MTT assay. These results of Morris water maze test and passive avoidance test indicated that 10 and 50 mg/kg of Loranthus parasiticus reversed scopolamine-induced memory deficits. Loranthus parasiticus also protected against glutamate-induced cytotoxicity in HT22 cells. As a result of in vitro test for elucidating possible mechanism, Loranthus parasiticus inhibited AChE activity, ROS production, and Ca2+ accumulation. Loranthus parasiticus showed memory enhancing effect and neuroprotective effect and these effects may be related to inhibition of AChE activity, ROS level, and Ca2+ influx.

  11. Deficits in executive and memory processes in delusional disorder: a case-control study.

    Directory of Open Access Journals (Sweden)

    Inmaculada Ibanez-Casas

    Full Text Available OBJECTIVE: Delusional disorder has been traditionally considered a psychotic syndrome that does not evolve to cognitive deterioration. However, to date, very little empirical research has been done to explore cognitive executive components and memory processes in Delusional Disorder patients. This study will investigate whether patients with delusional disorder are intact in both executive function components (such as flexibility, impulsivity and updating components and memory processes (such as immediate, short term and long term recall, learning and recognition. METHODS: A large sample of patients with delusional disorder (n = 86 and a group of healthy controls (n = 343 were compared with regard to their performance in a broad battery of neuropsychological tests including Trail Making Test, Wisconsin Card Sorting Test, Colour-Word Stroop Test, and Complutense Verbal Learning Test (TAVEC. RESULTS: When compared to controls, cases of delusional disorder showed a significantly poorer performance in most cognitive tests. Thus, we demonstrate deficits in flexibility, impulsivity and updating components of executive functions as well as in memory processes. These findings held significant after taking into account sex, age, educational level and premorbid IQ. CONCLUSIONS: Our results do not support the traditional notion of patients with delusional disorder being cognitively intact.

  12. Heterogeneity in development of aspects of working memory predicts longitudinal attention deficit hyperactivity disorder symptom change.

    Science.gov (United States)

    Karalunas, Sarah L; Gustafsson, Hanna C; Dieckmann, Nathan F; Tipsord, Jessica; Mitchell, Suzanne H; Nigg, Joel T

    2017-08-01

    The role of cognitive mechanisms in the clinical course of neurodevelopmental disorders is poorly understood. Attention Deficit Hyperactivity Disorder (ADHD) is emblematic in that numerous alterations in cognitive development are apparent, yet how they relate to changes in symptom expression with age is unclear. To resolve the role of cognitive mechanisms in ADHD, a developmental perspective that takes into account expected within-group heterogeneity is needed. The current study uses an accelerated longitudinal design and latent trajectory growth mixture models in a sample of children ages 7-13 years carefully characterized as with (n = 437) and without (n = 297) ADHD to (a) identify heterogeneous developmental trajectories for response inhibition, visual spatial working memory maintenance, and delayed reward discounting and (b) to assess the relationships between these cognitive trajectories and ADHD symptom change. Best-fitting models indicated multiple trajectory classes in both the ADHD and typically developing samples, as well as distinct relationships between each cognitive process and ADHD symptom change. Developmental change in response inhibition and delayed reward discounting were unrelated to ADHD symptom change, while individual differences in the rate of visual spatial working memory maintenance improvement predicted symptom remission in ADHD. Characterizing heterogeneity in cognitive development will be crucial for clarifying mechanisms of symptom persistence and recovery. Results here suggest working memory maintenance may be uniquely related to ADHD symptom improvement. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  13. Changes in pattern completion--a key mechanism to explain age-related recognition memory deficits?

    Science.gov (United States)

    Vieweg, Paula; Stangl, Matthias; Howard, Lorelei R; Wolbers, Thomas

    2015-03-01

    Accurate memory retrieval from partial or degraded input requires the reactivation of memory traces, a hippocampal mechanism termed pattern completion. Age-related changes in hippocampal integrity have been hypothesized to shift the balance of memory processes in favor of the retrieval of already stored information (pattern completion), to the detriment of encoding new events (pattern separation). Using a novel behavioral paradigm, we investigated the impact of cognitive aging (1) on recognition performance across different levels of stimulus completeness, and (2) on potential response biases. Participants were required to identify previously learned scenes among new ones. Additionally, all stimuli were presented in gradually masked versions to alter stimulus completeness. Both young and older adults performed increasingly poorly as the scenes became less complete, and this decline in performance was more pronounced in elderly participants indicative of a pattern completion deficit. Intriguingly, when novel scenes were shown, only the older adults showed an increased tendency to identify these as familiar scenes. In line with theoretical models, we argue that this reflects an age-related bias towards pattern completion. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Dietary Cholesterol Protects Anesthesia-Induced Cognitive Deficits ...

    African Journals Online (AJOL)

    learning and memory [6]. There are relatively few studies on memory retention following cholesterol diet. However, a recent investigation indicates that dietary cholesterol may retard long- term memory [7]. In addition to changes in learning and memory, studies have also shown that cholesterol can impact brain pathology,.

  15. Optical quantum memory based on electromagnetically induced transparency.

    Science.gov (United States)

    Ma, Lijun; Slattery, Oliver; Tang, Xiao

    2017-04-01

    Electromagnetically induced transparency (EIT) is a promising approach to implement quantum memory in quantum communication and quantum computing applications. In this paper, following a brief overview of the main approaches to quantum memory, we provide details of the physical principle and theory of quantum memory based specifically on EIT. We discuss the key technologies for implementing quantum memory based on EIT and review important milestones, from the first experimental demonstration to current applications in quantum information systems.

  16. Nitric oxide contributes to learning and memory deficits observed in hypothyroid rats during neonatal and juvenile growth

    Directory of Open Access Journals (Sweden)

    Mahmoud Hosseini

    2010-01-01

    Full Text Available INTRODUCTION: Severe cognitive impairment follows thyroid hormone deficiency during the neonatal period. The role of nitric oxide (NO in learning and memory has been widely investigated. METHODS: This study aimed to investigate the effect of hypothyroidism during neonatal and juvenile periods on NO metabolites in the hippocampi of rats and on learning and memory. Animals were divided into two groups and treated for 60 days from the first day of lactation. The control group received regular water, whereas animals in a separate group were given water supplemented with 0.03% methimazole to induce hypothyroidism. Male offspring were selected and tested in the Morris water maze. Samples of blood were collected to measure the metabolites of NO, NO2, NO3 and thyroxine. The animals were then sacrificed, and their hippocampi were removed to measure the tissue concentrations of NO2 and NO3. DISCUSSION: Compared to the control group's offspring, serum thyroxine levels in the methimazole group's offspring were significantly lower (P<0.01. In addition, the swim distance and time latency were significantly higher in the methimazole group (P<0.001, and the time spent by this group in the target quadrant (Q1 during the probe trial was significantly lower (P<0.001. There was no significant difference in the plasma levels of NO metabolites between the two groups; however, significantly higher NO metabolite levels in the hippocampi of the methimazole group were observed compared to controls (P<0.05. CONCLUSION: These results suggest that the increased NO level in the hippocampus may play a role in the learning and memory deficits observed in childhood hypothyroidism; however, the precise underlying mechanism(s remains to be elucidated.

  17. Combined lesions of hippocampus and subiculum Do not produce deficits in a nonspatial social olfactory memory task.

    Science.gov (United States)

    Burton, S; Murphy, D; Qureshi, U; Sutton, P; O'Keefe, J

    2000-07-15

    Rats transmit information to each other about which foods are safe to eat. If a rat smells a food odor on the breath of another rat, it is subsequently more likely to eat that food than an alternative. Work by Galef et al. (1988) has shown that the observer rat forms an association between two olfactory stimuli on the breath of the demonstrator rat that has eaten the food, the food odor and carbon disulphide, which is normally present in the rat breath. Bunsey and Eichenbaum (1995) claimed that the hippocampus/subicular region is required for the long-term retention of this nonspatial form of associative memory on the basis that combined lesions of the hippocampus and subiculum produced a deficit, but lesions of either structure alone did not. We report here a failure to repeat this finding. Rats with either combined lesions of the hippocampus and subiculum or with amygdala lesions were tested on their ability to remember this association either immediately (testing short-term memory) or after a 24 hr delay (testing long-term memory). Neither lesion group exhibited significant memory deficits on this nonspatial associative task at either test interval. In contrast, a deficit was observed on a spatial memory task (forced-choice alternation t-maze) for animals with combined lesions of the hippocampus and subiculum. These results contradict the findings of Bunsey and Eichenbaum (1995) and support the idea that the hippocampus/subicular region is not required for this nonspatial associative memory.

  18. Memory and learning sequelae in long-term survivors of acute lymphoblastic leukemia: Association with attention deficits

    International Nuclear Information System (INIS)

    Brouwers, P.; Poplack, D.

    1990-01-01

    A systematic study of verbal and nonverbal memory and learning was undertaken in long-term survivors of acute lymphoblastic leukemia to assess the incidence and pattern of impairments and to determine the relationship between these deficits and computed tomography (CT) brain scan abnormalities. Twenty-three children who had received cranial irradiation (2,400 cGy) and intrathecal chemotherapy as central nervous system (CNS) preventive therapy and who were off all therapy for at least 4 years were evaluated. On the basis of their CT brain scan findings, patients were divided into three groups: those with intracerebral calcifications (n = 5), those with cortical atrophy (n = 8), and those with normal CT findings (n = 10). Significant deficits in verbal memory (p less than 0.025) and verbal learning (p less than 0.05) were observed that were associated with the presence and type of CT brain scan abnormalities; the greatest impairments were observed in patients with calcifications. No significant differences between CT scan groups were found for nonverbal memory and learning. Previous evaluation of attentional processing in these patients using reaction time tests had revealed the presence of deficits primarily in the ability to sustain attention. Combining those data with findings from the present study showed that memory impairments, particularly those in short-term memory, were primarily attributable to an underlying attentional defect that affect the encoding stage of memory processing

  19. Role of the amygdala GABA-A receptors in ACPA-induced deficits during conditioned fear learning.

    Science.gov (United States)

    Nasehi, Mohammad; Roghani, Farnaz; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

    2017-05-01

    The basolateral amygdala (BLA) is a key structure for the emotional processing and storage of memories associated with emotional events, especially fear. On the other hand, endocannabinoids and CB1 receptors play a key role in learning and memory partly through long-term synaptic depression of GABAergic synapses in the BLA. The aim of this study was to explore the effects of GABA-A receptor agonist and antagonist in the fear-related memory acquisition deficits induced by ACPA (a selective CB1 cannabinoid receptor agonist). This study used context and tone fear conditioning paradigms to assess fear-related memory in male NMRI mice. Our results showed that the pre-training intraperitoneal administration of ACPA (0.5mg/kg) or (0.1 and 0.5mg/kg) decreased the percentage of freezing time in the contextual and tone fear conditioning, respectively. This indicated an impaired context- or tone-dependent fear memory acquisition. Moreover, the pre-training intra-BLA microinjection of GABA-A receptor agonist, muscimol, at 0.05 and 0.5μg/mouse impaired context-dependent fear memory, while the same doses of GABA-A antagonist, bicuculline, impaired tone-dependent fear memory. However, a subthreshold dose of muscimol or bicuculline increased the effect of ACPA at 0.1 and 0.5 or 0.05mg/kg on context- or tone-dependent fear memory, respectively. In addition, bicuculline at the lower dose increased the ACPA response on locomotor activity compared to its respective group. Such findings highlighted an interaction between BLA GABAergic and cannabinoidergic systems during the acquisition phase of conditioned fear memories. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Can Motivation Normalize Working Memory and Task Persistence in Children with Attention-Deficit/Hyperactivity Disorder? The Effects of Money and Computer-Gaming

    Science.gov (United States)

    Dovis, Sebastiaan; van der Oord, Saskia; Wiers, Reinout W.; Prins, Pier J. M.

    2012-01-01

    Visual-spatial "Working Memory" (WM) is the most impaired executive function in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Some suggest that deficits in executive functioning are caused by motivational deficits. However, there are no studies that investigate the effects of motivation on the visual-spatial WM of children with-…

  1. Can motivation normalize working memory and task persistence in children with attention-deficit/hyperactivity disorder? The effects of money and computer-gaming

    NARCIS (Netherlands)

    Dovis, S.; van der Oord, S.; Wiers, R.W.; Prins, P.J.M.

    2012-01-01

    Visual-spatial Working Memory (WM) is the most impaired executive function in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Some suggest that deficits in executive functioning are caused by motivational deficits. However, there are no studies that investigate the effects of

  2. Object Location and Object Recognition Memory Impairments, Motivation Deficits and Depression in a Model of Gulf War Illness

    Directory of Open Access Journals (Sweden)

    Bharathi eHattiangady

    2014-03-01

    Full Text Available Memory and mood deficits are the enduring brain-related symptoms in Gulf War illness (GWI. Both animal model and epidemiological investigations have indicated that these impairments in a majority of GW veterans are linked to exposures to chemicals such as pyridostigmine bromide (PB, an anti nerve gas drug, permethrin (PM, an insecticide and DEET (a mosquito repellant encountered during the Persian Gulf War-1. Our previous study in a rat model has shown that combined exposures to low doses of GWI-related (GWIR chemicals PB, PM and DEET with or without 5-minutes of restraint stress (a mild stress paradigm causes hippocampus-dependent spatial memory dysfunction in a water maze test and increased depressive-like behavior in a forced swim test. In this study, using a larger cohort of rats exposed to GWIR-chemicals and stress, we investigated whether the memory deficiency identified earlier in a water maze test is reproducible with an alternative and stress free hippocampus-dependent memory test such as the object location test. We also ascertained the possible co-existence of hippocampus-independent memory dysfunction using a novel object recognition test, and alterations in mood function with additional tests for motivation and depression. Our results provide new evidence that exposure to low doses of GWIR-chemicals and stress for four weeks causes deficits in hippocampus-dependent object location memory and perirhinal cortex-dependent novel object recognition memory. An open field test performed prior to other behavioral analyses revealed that memory impairments were not associated with increased anxiety or deficits in general motor ability. However, behavioral tests for mood function such as a voluntary physical exercise paradigm and a novelty suppressed feeding test showed decreased motivation and depression. Thus, exposure to GWIR-chemicals and stress causes both hippocampus-dependent and hippocampus-independent memory impairments as well as

  3. Aloe vera gel improves behavioral deficits and oxidative status in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Tabatabaei, Seyed Reza Fatemi; Ghaderi, Shahab; Bahrami-Tapehebur, Mohammad; Farbood, Yaghoob; Rashno, Masome

    2017-12-01

    Oxidative stress has a major role in progression of diabetes-related behavioral deficits. It has been suggested that Aloe vera has anti-diabetic, antioxidative, and neuroprotective effects. The present study was designed to determine the effects of Aloe vera gel on behavioral functions, oxidative status, and neuronal viability in the hippocampus of streptozotocin (STZ)-induced diabetic rats. Fifty five adult male Wistar rats were randomly divided into five groups, including: control (normal saline 8ml/kg/day; P.O.), diabetic (normal saline 8ml/kg/day; P.O.), Aloe vera gel (100mg/kg/day; P.O.), diabetic+Aloe vera gel (100mg/kg/day; P.O.) and diabetic+NPH insulin (10 IU/kg/day; S.C.). All treatments were started immediately following confirmation of diabetes in diabetic groups and were continued for eight weeks. Behavioral functions were evaluated by employing standard behavioral paradigms. Additionally, oxidative status and neuronal viability were assessed in the hippocampus. The results of behavioral tests showed that diabetes enhanced anxiety/depression-like behaviors, reduced exploratory and locomotor activities, decreased memory performance, and increased stress related behaviors. These changes in diabetic rats were accompanied by increasing oxidative stress and neuronal loss in the hippocampus. Interestingly, eight weeks of treatment with Aloe vera gel not only alleviated all the mentioned deficits related to diabetes, but in some aspects, it was even more effective than insulin. In conclusion, the results suggest that both interrelated hypoglycemic and antioxidative properties of Aloe vera gel are possible mechanisms that improve behavioral deficits and protect hippocampal neurons in diabetic animals. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Field Induced Memory Effects in Random Nematics

    Directory of Open Access Journals (Sweden)

    Amid Ranjkesh

    2014-01-01

    Full Text Available We studied numerically external field induced memory effects in randomly perturbed nematic liquid crystals. Random anisotropy nematic-type lattice model was used. The impurities imposing orientational disorder were randomly spatially distributed with the concentration p below the percolation threshold. Simulations were carried for finite temperatures, where we varied p, interaction strength between LC molecules, and impurities and external field B. In the {B,T} plane we determined lines separating short range—quasi long range and quasi long range—long range order. Furthermore, crossover regime separating external field and random field dominated regime was estimated. We calculated remanent nematic ordering in samples at B=0 as a function of the previously experienced external field strength B.

  5. Benefits of deep encoding in Alzheimer disease. Analysis of performance on a memory task using the Item Specific Deficit Approach.

    Science.gov (United States)

    Oltra-Cucarella, J; Pérez-Elvira, R; Duque, P

    2014-06-01

    the aim of this study is to test the encoding deficit hypothesis in Alzheimer disease (AD) using a recent method for correcting memory tests. To this end, a Spanish-language adaptation of the Free and Cued Selective Reminding Test was interpreted using the Item Specific Deficit Approach (ISDA), which provides three indices: Encoding Deficit Index, Consolidation Deficit Index, and Retrieval Deficit Index. We compared the performances of 15 patients with AD and 20 healthy control subjects and analysed results using either the task instructions or the ISDA approach. patients with AD displayed deficient encoding of more than half the information, but items that were encoded properly could be retrieved later with the help of the same semantic clues provided individually during encoding. Virtually all the information retained over the long-term was retrieved by using semantic clues. Encoding was shown to be the most impaired process, followed by retrieval and consolidation. Discriminant function analyses showed that ISDA indices are more sensitive and specific for detecting memory impairments in AD than are raw scores. These results indicate that patients with AD present impaired information encoding, but they benefit from semantic hints that help them recover previously learned information. This should be taken into account for intervention techniques focusing on memory impairments in AD. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  6. Anxiety modulates the relation between attention-deficit/hyperactivity disorder severity and working memory-related brain activity

    NARCIS (Netherlands)

    van der Meer, D.; Hoekstra, P.J.; van Rooij, D.; Winkler, A.M.; van Ewijk, H.; Heslenfeld, D.J.; Oosterlaan, J.; Faraone, S.V.; Franke, B.; Buitelaar, J.K.; Hartman, C.A.

    2017-01-01

    Objectives: Individuals with attention-deficit/hyperactivity disorder (ADHD) often have heightened levels of anxiety, which has been associated with worse performance on working memory tasks. Knowledge of the neural pathways underlying the combined presence of ADHD and anxiety may aid in a better

  7. Tempol protects sleep-deprivation induced behavioral deficits in aggressive male Long-Evans rats.

    Science.gov (United States)

    Solanki, Naimesh; Atrooz, Fatin; Asghar, Saman; Salim, Samina

    2016-01-26

    Earlier, we reported that elevated anxiety-like behavior and high aggression in aged retired breeder Long-Evans (L-E) rats was associated with increased plasma corticosterone and elevated oxidative stress levels. In the present study, we examined how this aged aggressive and anxious rat strain responds to acute sleep deprivation (24h) and whether their behaviors can be modulated via antioxidant tempol treatment. Four groups of L-E rats were utilized: naïve control (NC), tempol treated control (T+NC), sleep deprived (SD), tempol treated and sleep deprived (T+SD). Thus, two groups were treated with tempol (1mM in drinking water for 2 weeks) while the other two were not. Two groups were subjected to acute sleep deprivation (24h) using the columns-in-water model while the other two were not. Sleep deprivation induced anxiety-like behavior, led to significant depression-like behavior and short-term memory impairment in SD rats. And, decision-making behavior also was compromised in SD rats. These behavioral and cognitive impairments were prevented with tempol treatment in T+SD rats. Tempol treatment also reduced SD-induced increase in corticosterone and oxidative stress levels in T+SD rats. These results suggest potential involvement of oxidative stress mechanisms in regulation of sleep deprivation induced behavioral and cognitive deficits in male aged-aggressive rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Neural correlates of working memory deficits and associations to response inhibition in obsessive compulsive disorder.

    Science.gov (United States)

    Heinzel, Stephan; Kaufmann, Christian; Grützmann, Rosa; Hummel, Robert; Klawohn, Julia; Riesel, Anja; Bey, Katharina; Lennertz, Leonhard; Wagner, Michael; Kathmann, Norbert

    2018-01-01

    Previous research in patients with obsessive-compulsive disorder (OCD) has indicated performance decrements in working memory (WM) and response inhibition. However, underlying neural mechanisms of WM deficits are not well understood to date, and empirical evidence for a proposed conceptual link to inhibition deficits is missing. We investigated WM performance in a numeric n-back task with four WM load conditions during functional Magnetic Resonance Imaging (fMRI) in 51 patients with OCD and 49 healthy control participants who were matched for age, sex, and education. Additionally, a stop signal task was performed outside the MRI scanner in a subsample. On the behavioral level, a significant WM load by group interaction was found for both accuracy (p neural correlates of a load-dependent WM decrement in OCD in the supplementary motor area (SMA) and the inferior parietal lobule (IPL). Within the OCD sample, SMA-activity as well as n-back performance were correlated with stop signal task performance. Results from behavioral and fMRI-analyses indicate a reduced WM load-dependent modulation of neural activity in OCD and suggest a common neural mechanism for inhibitory dysfunction and WM decrements in OCD.

  9. Maltreatment increases spontaneous false memories but decreases suggestion-induced false memories in children.

    Science.gov (United States)

    Otgaar, Henry; Howe, Mark L; Muris, Peter

    2017-09-01

    We examined the creation of spontaneous and suggestion-induced false memories in maltreated and non-maltreated children. Maltreated and non-maltreated children were involved in a Deese-Roediger-McDermott false memory paradigm where they studied and remembered negative and neutral word lists. Suggestion-induced false memories were created using a misinformation procedure during which both maltreated and non-maltreated children viewed a negative video (i.e., bank robbery) and later received suggestive misinformation concerning the event. Our results showed that maltreated children had higher levels of spontaneous negative false memories but lower levels of suggestion-induced false memories as compared to non-maltreated children. Collectively, our study demonstrates that maltreatment both increases and decreases susceptibility to memory illusions depending on the type of false memory being induced. Statement of contribution What is already known on this subject? Trauma affects memory. It is unclear how trauma affects false memory. What does this study add? This study focuses on two types of false memories. © 2017 The Authors. British Journal of Developmental Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

  10. Using attribute amnesia to test the limits of hyper-binding and associative deficits in working memory.

    Science.gov (United States)

    McCormick-Huhn, John M; Chen, Hui; Wyble, Bradley P; Dennis, Nancy A

    2018-02-01

    Previous work has shown mixed evidence regarding age-related deficits for binding in working memory. The current study used the newly developed attribute amnesia effect (H. Chen & Wyble, 2015a) to test the associative-deficit hypothesis during working memory and to probe whether hyper-binding extends to include binding of de-selected information. In studies of attribute amnesia, participants use target attributes (e.g., identity, color) to demonstrate near ceiling levels of reporting of a second target attribute (e.g., location) across a series of trials (H. Chen & Wyble, 2015a, 2016). Yet, despite having just processed the target-defining attribute, they have difficulty reporting it on a surprise trial. This effect provides several predictions for associative binding in aging. The associative-deficit hypothesis predicts age-related decline on the surprise trial, whereas an extension of hyper-binding predicts age-related increase in performance in older adults. In Experiment 1, when working memory load was low, older adults demonstrated attribute amnesia equal to that found in younger adults. When load increased in Experiment 2, older adults again demonstrated attribute amnesia as well as an age deficit for reporting target attributes. In lieu of spontaneous binding, results suggest that expectancy plays a critical role in older adults' propensity to encode and bind target attributes in working memory. Results further suggest that expectancy alone is not enough for older adults to form bound representations when task demands are high. Taken together results revealed a boundary condition of hyper-binding and further provided conditional support for the associative-deficit hypothesis in working memory. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  11. Probiotic Mixture KF Attenuates Age-Dependent Memory Deficit and Lipidemia in Fischer 344 Rats.

    Science.gov (United States)

    Jeong, Jin-Ju; Kim, Kyung-Ah; Ahn, Young-Tae; Sim, Jae-Hun; Woo, Jae-Yeon; Huh, Chul-Sung; Kim, Dong-Hyun

    2015-09-01

    To investigate the memory-enhancing effect of lactic acid bacteria, we selected the probiotic mixture KF, which consisted of Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 (1 × 10(11) CFU/g of each strain), and investigated its antilipidemic and memoryenhancing effects in aged Fischer 344 rats. KF (1 × 10(10) CFU/rat/day), which was administered orally once a day (6 days per week) for 8 weeks, significantly inhibited age-dependent increases of blood triglyceride and reductions of HDL cholesterol (p KF restored agereduced spontaneous alternation in the Y-maze task to 94.4% of that seen in young rats (p KF treatment slightly, but not significantly, shortened the escape latency daily for 4 days. Oral administration of KF restored age-suppressed doublecortin and brain-derived neurotrophic factor expression in aged rats. Orally administered KF suppressed the expression of p16, p53, and cyclooxygenase-2, the phosphorylation of Akt and mTOR, and the activation of NF-κB in the hippocampus of the brain. These findings suggest that KF may ameliorate age-dependent memory deficit and lipidemia by inhibiting NF-κB activation.

  12. Growth hormone secretagogue receptor (GHS-R1a) knockout mice exhibit improved spatial memory and deficits in contextual memory.

    Science.gov (United States)

    Albarran-Zeckler, Rosie G; Brantley, Alicia Faruzzi; Smith, Roy G

    2012-06-15

    Although the hormone ghrelin is best known for its stimulatory effect on appetite and regulation of growth hormone release, it is also reported to have beneficial effects on learning and memory formation in mice. Nevertheless, controversy exists about whether endogenous ghrelin acts on its receptors in extra-hypothalamic areas of the brain. The ghrelin receptor (GHS-R1a) is co-expressed in neurons that express dopamine receptor type-1 (DRD1a) and type-2 (DRD2), and we have shown that a subset of GHS-R1a, which are not occupied by the agonist (apo-GHSR1a), heterodimerize with these two receptors to regulate dopamine signaling in vitro and in vivo. To determine the consequences of ghsr ablation on brain function, congenic ghsr -/- mice on the C57BL6/J background were subjected to a battery of behavioral tests. We show that the ghsr -/- mice exhibit normal balance, movement, coordination, and pain sensation, outperform ghsr +/+ mice in the Morris water maze, but show deficits in contextual fear conditioning. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses subcronic PCP-induced deficits in the novel object recognition task in rats

    DEFF Research Database (Denmark)

    Nielsen, Trine Damgaard; Larsen, Dorrit Bjerg; Hansen, Suzanne Lisbet

    2010-01-01

    deficit in female Lister hooded rats in teh novel object recognition (NOR) task. Here we show that positive modulation of AMPA receptor (AMPAR) mediated glutamate transmission alleviates cognitive deficits induced by sub-chronic PCP treatment. Female Lister hooded rats were treated sub......Cognitive deficits are a major clinical unmet need in schizophrenia. The psychotomimetic drug phencyclicline (PCP) is widely applied in rodents to mimic symptoms of schizophrenia, including cognitive deficits. Precious studies have shown that sub-chronic PCP induces an enduring episodic memory......-cbronic PCP treatment induced a significant decrease in the discrimination index (DI) and both ampakines CX546 and CX516 were able to reverse this diruption of object memory in rats in the novel object recognition task. These data suggest that positive AMPAR modulation may represent a mechanism for treatment...

  14. An International Survey of Assessment Practices for Short-Term and Working Memory Deficits in Aphasia.

    Science.gov (United States)

    Salis, Christos; Murray, Laura; Bakas, Katrina

    2018-02-20

    Recent research has highlighted the clinical relevance of understanding the nature of short-term memory (STM) and working memory (WM) deficits in persons with aphasia and the way these deficits affect linguistic processing and functional communication in activities of daily living. The psychometric properties of tests commonly used to identify STM/WM problems in individuals with aphasia, however, have been questioned. No previous study has sought to investigate assessment practices and attitudes by speech-language pathologists involved in aphasia management. Accordingly, the aims of this study were (a) to investigate both attitudes toward STM/WM assessment in individuals with aphasia, as well as the types and frequency of STM/WM tests used with individuals with aphasia, and (b) to explore factors (e.g., educational background) that may influence STM/WM assessment practices. Respondents recruited via professional and aphasia support organizations completed an online survey. The survey elicited information about the respondents' demographic and clinical backgrounds and STM/WM assessment clinical practices and views, including frequency and preferred use of specific STM/WM tests. The majority of respondents reported regular use of STM/WM tests as part of aphasia management. Positive attitudes toward STM/WM assessments were also reported. The most popular rankings of tests were the Cognitive Linguistic Quick Test (Helm-Estabrooks, 2001), the Comprehensive Aphasia Test (Swinburn, Porter, & Howard, 2005), and the Token Test (McNeil & Prescott, 1978). Results suggested limited knowledge about measures that assess self-perceptions of functional memory abilities. Regression analyses showed that the frequency of reported STM/WM test use was similar between clinicians and dual-role researchers/clinicians, but their attitudes toward the value of STM/WM differed. U.S. and UK respondents reported similar assessment practices. It is reassuring that STM/WM is taken into

  15. Systematic Review of Neuropsychological Rehabilitation for Prospective Memory Deficits as a Consequence of Acquired Brain Injury.

    Science.gov (United States)

    Mahan, Steven; Rous, Rebecca; Adlam, Anna

    2017-01-19

    Prospective memory (PM) impairments are common following acquired brain injury (ABI). PM is the ability to keep a goal in mind for future action and interventions have the potential to increase independence. This review aimed to evaluate studies examining PM rehabilitation approaches in adults and children with ABI. Relevant literature was identified using PsycARTICLES (1894 to present), PsycINFO (1880 to present), the Cochrane Library (1972 to present), MEDLINE PubMed, reference lists from relevant journal articles, and searches of key journals. Literature searches were conducted using variants of the terms brain injury, stroke, encephalitis, meningitis, and tumor, combined with variants of the terms rehabilitation and prospective memory. Of the 435 papers identified, 11 were included in the review. Findings demonstrated a variety of interventions to alleviate PM deficits, including compensatory strategies (e.g., external memory aids) that provide either content-specific or content-free cueing, and remediation strategies (e.g., meta-cognitive training programs) aimed at improving the self-monitoring of personal goals. Risk of bias for individual studies was considered and the strengths and limitations of each of the included studies and the review itself were discussed. Interventions used with adults can be effective; PM abilities can be improved by using simple reminder systems and performance can be generalized to facilitate everyday PM functioning. There is, however, a lack of research of PM interventions conducted with children with ABI, and pediatric interventions need to consider on-going cognitive maturation. (JINS, 2017, 22, 1-12).

  16. Modafinil improves methamphetamine-induced object recognition deficits and restores prefrontal cortex ERK signaling in mice.

    Science.gov (United States)

    González, Betina; Raineri, Mariana; Cadet, Jean Lud; García-Rill, Edgar; Urbano, Francisco J; Bisagno, Veronica

    2014-12-01

    Chronic use of methamphetamine (METH) leads to long-lasting cognitive dysfunction in humans and in animal models. Modafinil is a wake-promoting compound approved for the treatment of sleeping disorders. It is also prescribed off label to treat METH dependence. In the present study, we investigated whether modafinil could improve cognitive deficits induced by sub-chronic METH treatment in mice by measuring visual retention in a Novel Object Recognition (NOR) task. After sub-chronic METH treatment (1 mg/kg, once a day for 7 days), mice performed the NOR task, which consisted of habituation to the object recognition arena (5 min a day, 3 consecutive days), training session (2 equal objects, 10 min, day 4), and a retention session (1 novel object, 5 min, day 5). One hour before the training session, mice were given a single dose of modafinil (30 or 90 mg/kg). METH-treated mice showed impairments in visual memory retention, evidenced by equal preference of familiar and novel objects during the retention session. The lower dose of modafinil (30 mg/kg) had no effect on visual retention scores in METH-treated mice, while the higher dose (90 mg/kg) rescued visual memory retention to control values. We also measured extracellular signal-regulated kinase (ERK) phosphorylation in medial prefrontal cortex (mPFC), hippocampus, and nucleus accumbens (NAc) of METH- and vehicle-treated mice that received modafinil 1 h before exposure to novel objects in the training session, compared to mice placed in the arena without objects. Elevated ERK phosphorylation was found in the mPFC of vehicle-treated mice, but not in METH-treated mice, exposed to objects. The lower dose of modafinil had no effect on ERK phosphorylation in METH-treated mice, while 90 mg/kg modafinil treatment restored the ERK phosphorylation induced by novelty in METH-treated mice to values comparable to controls. We found neither a novelty nor treatment effect on ERK phosphorylation in hippocampus or NAc of vehicle

  17. Working memory in attention deficit/hyperactivity disorder is characterized by a lack of specialization of brain function.

    Directory of Open Access Journals (Sweden)

    Catherine Fassbender

    Full Text Available Working memory impairments are frequent in Attention Deficit/Hyperactivity Disorder (ADHD and create problems along numerous functional dimensions. The present study utilized the Visual Serial Addition Task (VSAT and functional magnetic resonance imaging (fMRI to explore working memory processes in thirteen typically developing (TD control and thirteen children with ADHD, Combined type. Analysis of Variance (ANOVA was used to examine both main effects and interactions. Working memory-specific activity was found in TD children in the bilateral prefrontal cortex. In contrast the within-group map in ADHD did not reveal any working-memory specific regions. Main effects of condition suggested that the right middle frontal gyrus (BA6 and the right precuneus were engaged by both groups during working memory processing. Group differences were driven by significantly greater, non-working memory-specific, activation in the ADHD relative to TD group in the bilateral insula extending into basal ganglia and the medial prefrontal cortex. A region of interest analysis revealed a region in left middle frontal gyrus that was more active during working memory in TD controls. Thus, only the TD group appeared to display working memory-modulated brain activation. In conclusion, children with ADHD demonstrated reduced working memory task specific brain activation in comparison to their peers. These data suggest inefficiency in functional recruitment by individuals with ADHD represented by a poor match between task demands and appropriate levels of brain activity.

  18. Working memory in attention deficit/hyperactivity disorder is characterized by a lack of specialization of brain function.

    Science.gov (United States)

    Fassbender, Catherine; Schweitzer, Julie B; Cortes, Carlos R; Tagamets, Malle A; Windsor, T Andrew; Reeves, Gloria M; Gullapalli, Rao

    2011-01-01

    Working memory impairments are frequent in Attention Deficit/Hyperactivity Disorder (ADHD) and create problems along numerous functional dimensions. The present study utilized the Visual Serial Addition Task (VSAT) and functional magnetic resonance imaging (fMRI) to explore working memory processes in thirteen typically developing (TD) control and thirteen children with ADHD, Combined type. Analysis of Variance (ANOVA) was used to examine both main effects and interactions. Working memory-specific activity was found in TD children in the bilateral prefrontal cortex. In contrast the within-group map in ADHD did not reveal any working-memory specific regions. Main effects of condition suggested that the right middle frontal gyrus (BA6) and the right precuneus were engaged by both groups during working memory processing. Group differences were driven by significantly greater, non-working memory-specific, activation in the ADHD relative to TD group in the bilateral insula extending into basal ganglia and the medial prefrontal cortex. A region of interest analysis revealed a region in left middle frontal gyrus that was more active during working memory in TD controls. Thus, only the TD group appeared to display working memory-modulated brain activation. In conclusion, children with ADHD demonstrated reduced working memory task specific brain activation in comparison to their peers. These data suggest inefficiency in functional recruitment by individuals with ADHD represented by a poor match between task demands and appropriate levels of brain activity.

  19. Mitochondrial modulators improve lipid composition and attenuate memory deficits in experimental model of Huntington's disease.

    Science.gov (United States)

    Mehrotra, Arpit; Sood, Abhilasha; Sandhir, Rajat

    2015-12-01

    3-Nitropropionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase and induces neuropathological changes similar to those observed in Huntington's disease (HD). The objective of the present study was to investigate neuroprotective effect of mitochondrial modulators; alpha-lipoic acid (ALA) and acetyl-L-carnitine (ALCAR) on 3-NP-induced alterations in mitochondrial lipid composition, mitochondrial structure and memory functions. Experimental model of HD was developed by administering 3-NP at sub-chronic doses, twice daily for 17 days. The levels of conjugated dienes, cholesterol and glycolipids were significantly increased, whereas the levels of phospholipids (phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine) including cardiolipin were significantly decreased in the mitochondria isolated from the striatum of 3-NP-treated animals. In addition, the difference in molecular composition of each phospholipid class was also evaluated using mass spectrometry. Mitochondria lipid from 3-NP-treated animals showed increased cholesterol to phospholipid ratio, suggesting decreased mitochondrial membrane fluidity. 3-NP administration also resulted in ultra-structural changes in mitochondria, accompanied by swelling as assessed by transmission electron microscopy. The 3-NP administered animals had impaired spatial memory evaluated using elevated plus maze test. However, combined supplementation with ALA + ALCAR for 21 days normalized mitochondrial lipid composition, improved mitochondrial structure and ameliorated memory impairments in 3-NP-treated animals, suggesting an imperative role of these two modulators in combination in the management of HD.

  20. Impaired spatial pattern separation performance in temporal lobe epilepsy is associated with visuospatial memory deficits and hippocampal volume loss.

    Science.gov (United States)

    Reyes, Anny; Holden, Heather M; Chang, Yu-Hsuan A; Uttarwar, Vedang S; Sheppard, David P; DeFord, Nicole E; DeJesus, Shannon Yandall; Kansal, Leena; Gilbert, Paul E; McDonald, Carrie R

    2018-03-01

    Individuals with chronic temporal lobe epilepsy (TLE) experience episodic memory deficits that may be progressive in nature. These memory decrements have been shown to increase with the extent of hippocampal damage, a hallmark feature of TLE. Pattern separation, a neural computational mechanism thought to play a role in episodic memory formation, has been shown to be negatively affected by aging and in individuals with known hippocampal dysfunction. Despite the link between poor pattern separation performance and episodic memory deficits, behavioral pattern separation has not been examined in patients with TLE. We examined pattern separation performance in a group of 22 patients with medically-refractory TLE and 20 healthy adults, using a task hypothesized to measure spatial pattern separation with graded levels of spatial interference. We found that individuals with TLE showed less efficient spatial pattern separation performance relative to healthy adults. Poorer spatial pattern separation performance in TLE was associated with poorer visuospatial memory, but only under high interference conditions. In addition, left hippocampal atrophy was associated with poor performance in the high interference condition in TLE. These data suggest that episodic memory impairments in patients with chronic, refractory TLE may be partially due to less efficient pattern separation, which likely reflects their underlying hippocampal dysfunction. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Protection by Acorus calamus against prenatal irradiation induced developmental and neurophysiological deficits

    International Nuclear Information System (INIS)

    Chetana, M.; Sulochana, B.; Uma Devi, P.

    2004-01-01

    Exposure of the developing fetus to ionizing radiation causes severe consequences ranging from stunting of growth to postnatal deficits in development, morphology and behavior. Present experiment was planned to study the effect of a medicinal plant, Acorus calamus on prenatal irradiation induced developmental and adult neurophysiological deficits

  2. Time perception impairment in early-to-moderate stages of Huntington's disease is related to memory deficits.

    Science.gov (United States)

    Righi, Stefania; Galli, Luca; Paganini, Marco; Bertini, Elisabetta; Viggiano, Maria Pia; Piacentini, Silvia

    2016-01-01

    Huntington's disease (HD) primarily affects striatum and prefrontal dopaminergic circuits which are fundamental neural correlates of the timekeeping mechanism. The few studies on HD mainly investigated motor timing performance in second durations. The present work explored time perception in early-to-moderate symptomatic HD patients for seconds and milliseconds with the aim to clarify which component of the scalar expectancy theory (SET) is mainly responsible for HD timing defect. Eleven HD patients were compared to 11 controls employing two separate temporal bisection tasks in second and millisecond ranges. Our results revealed the same time perception deficits for seconds and milliseconds in HD patients. Time perception impairment in early-to-moderate stages of Huntington's disease is related to memory deficits. Furthermore, both the non-systematical defect of temporal sensitivity and the main impairment of timing performance in the extreme value of the psychophysical curves suggested an HD deficit in the memory component of the SET. This result was further confirmed by the significant correlations between time perception performance and long-term memory test scores. Our findings added important preliminary data for both a deeper comprehension of HD time-keeping deficits and possible implications on neuro-rehabilitation practices.

  3. Dose-Dependent Effect of Curcumin on Learning and Memory Deficit in Kainate-Epileptic Rats

    Directory of Open Access Journals (Sweden)

    Zahra Kiasalari

    2014-09-01

    Full Text Available Background & objectives : Epileptic seizures accompany disturbances in learning, memory, and cognitive skills. With regard to antiepileptic potential of curcumin and its beneficial effect on memory, the effect of its administration on learning and memory in kainate-epileptic rats was investigated.   Methods: Forty male rats were divided into sham, positive control ( valproate-treated epileptic, epileptic, and two curcumin-treated epileptic groups. Rat model of epilepsy was induced by unilateral intrahippocampal administration of 4 μg of kainate per rat. Rats received intraperitoneal injection of curcumin (50 and 100 mg/kg daily for 1 week before surgery. For evaluation of learning and memory, initial (IL and step-through latencies (STL were determined using passive avoidance test and alternation behavior percentage was obtained according to Y maze test.   Results: Regarding IL, there was no significant difference between the groups. In contrast, STL significantly decreased in curcumin-50-treated epileptic group (p<0.05 (a change from 263.1 to 184.5 s. However, this parameter significantly increased in curcumin-100-treated epileptic group as compared to epileptic group (p<0.01 (a change from 263.1 to 220.3 s. In addition, STL was also significantly higher in valproic acid-treated epileptic group versus epileptic group (p<0.05 (a change from 145.7 to 210.3 s. Alternation percentage was also significantly higher in curcumin-50- and curcumin-100-treated epileptic groups relative to epileptic group (p<0.05 (a change from 60.5 to 77.6 and 80.3%.   Conclusion: Curcumin could dose-dependently enhance the consolidation and recall in epileptic animals and could improve spatial memory in such animals.

  4. Protective Effect of Porcine Cerebral Hydrolysate Peptides on Learning and Memory Deficits and Oxidative Stress in Lead-Exposed Mice.

    Science.gov (United States)

    Zou, Ye; Feng, Weiwei; Wang, Wei; Chen, Yao; Zhou, Zhaoxiang; Li, Qian; Zhao, Ting; Mao, Guanghua; Wu, Xiangyang; Yang, Liuqing

    2015-12-01

    In this study, lead acetate solution and porcine cerebral hydrolysate peptides (PCHPs) were administered to developing mice. Porcine cerebral protein pretreated by ultrasound was hydrolyzed with alcalase, and 11 peptide fragments were obtained by Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of PCHPs. Our data showed that PCHPs significantly decreased Pb2+-induced spontaneous locomotor activity, latencies to reach the platform, and the time in target quadrant. It also decreased the accumulation of lead in the blood and brain of Pb2+-exposed developing mice. Co-administration of PCHPs and dimercaptosuccinic acid (DMSA) did not only reduce the accumulation of lead in blood but also increased the absorption of zinc and iron in Pb2+-exposed mice. Administration of PCHPs individually significantly enhanced hematopoietic parameters compared with the Pb2+-exposed group. PCHPs significantly reduced the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) but increased glutathione (GSH) content and anti-oxidant enzymes and nitric oxide synthase (NOS) activities in Pb2+-exposed brain. Our findings suggest that PCHPs have the ability to protect against Pb2+-exposed learning and memory deficits and oxidative damage.

  5. Age-dependent and -independent changes in attention-deficit/hyperactivity disorder (ADHD) during spatial working memory performance.

    Science.gov (United States)

    Bollmann, Steffen; Ghisleni, Carmen; Poil, Simon-Shlomo; Martin, Ernst; Ball, Juliane; Eich-Höchli, Dominique; Klaver, Peter; O'Gorman, Ruth L; Michels, Lars; Brandeis, Daniel

    2017-06-01

    Attention-deficit/hyperactivity disorder (ADHD) has been associated with spatial working memory as well as frontostriatal core deficits. However, it is still unclear how the link between these frontostriatal deficits and working memory function in ADHD differs in children and adults. This study examined spatial working memory in adults and children with ADHD, focussing on identifying regions demonstrating age-invariant or age-dependent abnormalities. We used functional magnetic resonance imaging to examine a group of 26 children and 35 adults to study load manipulated spatial working memory in patients and controls. In comparison to healthy controls, patients demonstrated reduced positive parietal and frontostriatal load effects, i.e., less increase in brain activity from low to high load, despite similar task performance. In addition, younger patients showed negative load effects, i.e., a decrease in brain activity from low to high load, in medial prefrontal regions. Load effect differences between ADHD and controls that differed between age groups were found predominantly in prefrontal regions. Age-invariant load effect differences occurred predominantly in frontostriatal regions. The age-dependent deviations support the role of prefrontal maturation and compensation in ADHD, while the age-invariant alterations observed in frontostriatal regions provide further evidence that these regions reflect a core pathophysiology in ADHD.

  6. Disruptions of working memory and inhibition mediate the association between exposure to institutionalization and symptoms of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Tibu, F; Sheridan, M A; McLaughlin, K A; Nelson, C A; Fox, N A; Zeanah, C H

    2016-02-01

    Young children raised in institutions are exposed to extreme psychosocial deprivation that is associated with elevated risk for psychopathology and other adverse developmental outcomes. The prevalence of attention deficit hyperactivity disorder (ADHD) is particularly high in previously institutionalized children, yet the mechanisms underlying this association are poorly understood. We investigated whether deficits in executive functioning (EF) explain the link between institutionalization and ADHD. A sample of 136 children (aged 6-30 months) was recruited from institutions in Bucharest, Romania, and 72 never institutionalized community children matched for age and gender were recruited through general practitioners' offices. At 8 years of age, children's performance on a number of EF components (working memory, response inhibition and planning) was evaluated. Teachers completed the Health and Behavior Questionnaire, which assesses two core features of ADHD, inattention and impulsivity. Children with history of institutionalization had higher inattention and impulsivity than community controls, and exhibited worse performance on working memory, response inhibition and planning tasks. Lower performances on working memory and response inhibition, but not planning, partially mediated the association between early institutionalization and inattention and impulsivity symptom scales at age 8 years. Institutionalization was associated with decreased EF performance and increased ADHD symptoms. Deficits in working memory and response inhibition were specific mechanisms leading to ADHD in previously institutionalized children. These findings suggest that interventions that foster the development of EF might reduce risk for psychiatric problems in children exposed to early deprivation.

  7. Timosaponin B-II ameliorates scopolamine-induced cognition deficits by attenuating acetylcholinesterase activity and brain oxidative damage in mice.

    Science.gov (United States)

    Zhao, Xu; Liu, Chunmei; Qi, Yu; Fang, Lina; Luo, Jie; Bi, Kaishun; Jia, Ying

    2016-12-01

    Timosaponin B-II (TB-II) is a main active saponin isolated from the rhizome of Anemarrhena asphodeloides Bge., which is widely used in traditional Chinese medicine. In this study, the effect of TB-II on learning and memory was investigated in a scopolamine-induced mouse model of Alzheimer's disease. The results of behavioral tests indicated that TB-II significantly increased the spontaneous alternation in the Y-maze test, and reversed the shortening of step-through latency induced by scopolamine in the passive avoidance test, showing protective effects on short-term and working memory. In the Morris water maze test, TB-II reduced the escape latency time in the training trial, and increased the swimming time in the target quadrant in the probe trial. Biochemical data demonstrated that TB-II significantly inhibited acetylcholinesterase (AChE) activity in the cerebral cortex and hippocampus of mice. Moreover, TB-II markably attenuated the reduction in glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, and decreased malondialdehyde (MDA) levels, which are key biomarkers of brain oxidative stress. These results indicated that TB-II offers protection against scopolamine-induced deficits in learning and memory, possibly by inhibiting AChE and preventing oxidative stress damage. The findings suggested that TB-II has a potential therapeutic effect on cognitive and behavioral impairment.

  8. Icariin Attenuates Synaptic and Cognitive Deficits in an Aβ1–42-Induced Rat Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Chenxia Sheng

    2017-01-01

    Full Text Available Icariin (ICA, a prenylated flavanol glycoside present in abundant quantities in Epimedium sagittatum, has shown promise in the treatment and prevention of Alzheimer’s disease. Damage to synaptic plasticity induced by amyloid-beta-mediated neurotoxicity is considered a main pathological mechanism driving the learning and memory deficits present in patients with Alzheimer’s disease. This study investigated the neuroprotective effects of icariin in an Aβ1–42-induced rat model of Alzheimer’s disease. Our results showed that Aβ1–42 injection induced loss of learning and memory behaviour in the Morris water maze, which could be reversed with intragastric administration of ICA. Furthermore, ICA reversed decreases in PSD-95, BDNF, pTrkB, pAkt, and pCREB expressions and prevented deterioration of synaptic interface structure. These findings indicate that ICA may improve synaptic plasticity through the BDNF/TrkB/Akt pathway and provide further evidence for its clinical application to improve learning and memory in patients with Alzheimer’s disease.

  9. Learning induces the translin/trax RNase complex to express activin receptors for persistent memory.

    Science.gov (United States)

    Park, Alan Jung; Havekes, Robbert; Fu, Xiuping; Hansen, Rolf; Tudor, Jennifer C; Peixoto, Lucia; Li, Zhi; Wu, Yen-Ching; Poplawski, Shane G; Baraban, Jay M; Abel, Ted

    2017-09-20

    Long-lasting forms of synaptic plasticity and memory require de novo protein synthesis. Yet, how learning triggers this process to form memory is unclear. Translin/trax is a candidate to drive this learning-induced memory mechanism by suppressing microRNA-mediated translational silencing at activated synapses. We find that mice lacking translin/trax display defects in synaptic tagging, which requires protein synthesis at activated synapses, and long-term memory. Hippocampal samples harvested from these mice following learning show increases in several disease-related microRNAs targeting the activin A receptor type 1C (ACVR1C), a component of the transforming growth factor-β receptor superfamily. Furthermore, the absence of translin/trax abolishes synaptic upregulation of ACVR1C protein after learning. Finally, synaptic tagging and long-term memory deficits in mice lacking translin/trax are mimicked by ACVR1C inhibition. Thus, we define a new memory mechanism by which learning reverses microRNA-mediated silencing of the novel plasticity protein ACVR1C via translin/trax.

  10. Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil.

    Directory of Open Access Journals (Sweden)

    Diansan Su

    Full Text Available Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2% for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE, choline acetylase (ChAT and α7 nicotinic receptor (α7-nAChR were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or α7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane.

  11. Arbutus andrachne L. Reverses Sleep Deprivation-Induced Memory Impairments in Rats.

    Science.gov (United States)

    Alzoubi, Karem H; Malkawi, Bayan S; Khabour, Omar F; El-Elimat, Tamam; Alali, Feras Q

    2018-02-01

    Sleep deprivation (SD) is associated with cognitive deficits. It was found to affect the hippocampus region of the brain by impairing memory formation. This impairment is suggested to be caused by elevation in oxidative stress in the body, including the brain during SD. It was hypothesized that the methanolic extract of the fruits of Arbutus andrachne L. (Ericaceae) will prevent chronic SD-induced impairment of hippocampal memory via its antioxidative properties. The methanolic extract of the fruits of A. andrachne was evaluated for its beneficial properties to reverse SD-induced cognitive impairment in rats. Animals were sleep deprived for 8 weeks using a multiple platform model. The extract was administered i.p. at three doses (50, 200, and 500 mg/kg). Behavioral studies were conducted to test the spatial learning and memory using radial arm water maze (RAWM). In addition, the hippocampus was dissected to analyze the following oxidative stress markers: glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG, glutathione peroxidase (GPx), and catalase. Chronic SD impaired short- and long-term memories (P memory impairment induced by SD while such treatment prevented short-term memory impairment only at 200 and 500 mg/kg dose levels. Moreover, A. andrachne fruit extract normalized the reduction in the hippocampus GSH/GSSG ratio and activity of GPx, and catalase (P sleep deprivation. Chronic sleep deprivation impaired both short- and long-term memory formation, while methanolic extract of A. andrachne fruits reversed this impairment, probably through normalizing oxidative stress in the hippocampus.

  12. The effects of Tabernaemontana divaricata root extract on amyloid beta-peptide 25-35 peptides induced cognitive deficits in mice.

    Science.gov (United States)

    Nakdook, Walika; Khongsombat, Onrawee; Taepavarapruk, Pornnarin; Taepavarapruk, Niwat; Ingkaninan, Kornkanok

    2010-07-06

    ETHNOPHAMACOLOGICAL RELEVANCE: Tabernaemontana divaricata (TD), a Thai medicinal herb, has been widely used as an analgesic, sedative, or a cough syrup. Moreover, it has been used in traditional rejuvenation remedies as for preventing forgetfulness and improving the memory. The present study aimed to determine the effect of TD on Abeta25-35 peptides induced cognitive deficits and acetylcholinesterase activity in mice. Mice were pretreated with TDE (250, 500 and 1,000 mg/kg body weight) for 28 days and then received i.c.v. injection of Abeta25-35 peptides. Cognitive performance was evaluated using the Morris water maze (MWM) and step-down avoidance test. The Ellman's colorimetric method was used to investigate the levels of cortical and hippocampal AChE activity. Abeta25-35 peptides induced the memory impairment and the increased levels of cortical and hippocampal AChE activity. The consumption of TDE significantly improved the memory impairment and attenuated the brain levels of AChE activity induced by Abeta25-35 peptides. These findings suggest that subchronic administration of TDE might prevent the Abeta25-35 peptides induced memory deficits by decreasing the AChE activity level. Therefore TDE could potentially be one of nootropic supplements for those elderly people suffering from dementia such as the AD patients. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Working Memory Training in the Form of Structured Games in Children with Attention Deficit Hyperactivity Disorder

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    Fatemeh Khalili Kermani

    2016-12-01

    Full Text Available Objective: In this study, a new training method of working memory (WM was used in the form of structured games, and the effect of training was evaluated with a controlled design. The training method of WM in the form of structured games includes 20 sets of structured games that can improve WM and performance of executive functions.Method: Sixty children with attention deficit hyperactivity disorder (ADHD aged 8.5 to 11.2 years (35 boys, using no stimulant medication were selected. We randomly assigned 30 participants to the experimental group and provided them with WM training. The training was in the form of structured games and was offered to the participants in two 60-minute sessions weekly for 12 weeks. Other participants were assigned to the control group, receiving no treatment. All the participants were also evaluated at follow-up 6 months later. The main measures were the Child Behavior Checklist (CBCL, the Digit Span and Symbol Search B subscale of the Wechsler Intelligence Scale for Children (WISC-IV; and scores of dictation and mathematics were used in terms of pre and post-test.Results: The results of the t-test revealed a significant improvement in the post-test measures as well as a significant reduction of parents’ reports of inattentiveness, and improvement in academic performance in the experimental group. However, no significant changes were found in the control group.Conclusion: The academic and working memory improvements were primarily due to the training method of WM. Our findings suggest that the training method of WM in the form of structured games may be a practical method for treating children with ADHD, but it needs to be further investigated.

  14. Attentional control activation relates to working memory in attention-deficit/hyperactivity disorder.

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    Burgess, Gregory C; Depue, Brendan E; Ruzic, Luka; Willcutt, Erik G; Du, Yiping P; Banich, Marie T

    2010-04-01

    Attentional control difficulties in individuals with attention-deficit/hyperactivity disorder (ADHD) might reflect poor working memory (WM) ability, especially because WM ability and attentional control rely on similar brain regions. The current study examined whether WM ability might explain group differences in brain activation between adults with ADHD and normal control subjects during attentional demand. Participants were 20 adults with ADHD combined subtype with no comorbid psychiatric or learning disorders and 23 control subjects similar in age, IQ, and gender. The WM measures were obtained from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-Revised. Brain activation was assessed with functional magnetic resonance imaging (fMRI) while performing a Color-Word Stroop task. Group differences in WM ability explained a portion of the activation in left dorsolateral prefrontal cortex (DLPFC), which has been related to the creation and maintenance of an attentional set for task-relevant information. In addition, greater WM ability predicted increased activation of brain regions related to stimulus-driven attention and response selection processes in the ADHD group but not in the control group. The inability to maintain an appropriate task set in young adults with combined type ADHD, associated with decreased activity in left DLPFC, might in part be due to poor WM ability. Furthermore, in individuals with ADHD, higher WM ability might relate to increased recruitment of stimulus-driven attention and response selection processes, perhaps as a compensatory strategy. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Sleep disturbance induces neuroinflammation and impairment of learning and memory.

    Science.gov (United States)

    Zhu, Biao; Dong, Yuanlin; Xu, Zhipeng; Gompf, Heinrich S; Ward, Sarah A P; Xue, Zhanggang; Miao, Changhong; Zhang, Yiying; Chamberlin, Nancy L; Xie, Zhongcong

    2012-12-01

    Hospitalized patients can develop cognitive function decline, the mechanisms of which remain largely to be determined. Sleep disturbance often occurs in hospitalized patients, and neuroinflammation can induce learning and memory impairment. We therefore set out to determine whether sleep disturbance can induce neuroinflammation and impairment of learning and memory in rodents. Five to 6-month-old wild-type C57BL/6J male mice were used in the studies. The mice were placed in rocking cages for 24 h, and two rolling balls were present in each cage. The mice were tested for learning and memory function using the Fear Conditioning Test one and 7 days post-sleep disturbance. Neuroinflammation in the mouse brain tissues was also determined. Of the Fear Conditioning studies at one day and 7 days after sleep disturbance, twenty-four hour sleep disturbance decreased freezing time in the context test, which assesses hippocampus-dependent learning and memory; but not the tone test, which assesses hippocampus-independent learning and memory. Sleep disturbance increased pro-inflammatory cytokine IL-6 levels and induced microglia activation in the mouse hippocampus, but not the cortex. These results suggest that sleep disturbance induces neuroinflammation in the mouse hippocampus, and impairs hippocampus-dependent learning and memory in mice. Pending further studies, these findings suggest that sleep disturbance-induced neuroinflammation and impairment of learning and memory may contribute to the development of cognitive function decline in hospitalized patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Validation of distinct amnesic and executive type memory deficit in a psychiatric sample based on retrieval performance.

    Science.gov (United States)

    Egeland, Jens; Landrø, Nils Inge; Sundet, Kjetil; Asbjørnsen, Arve; Lund, Anders; Roness, Atle; Rund, Bjørn Rishovd

    2005-04-01

    Studies of localized brain dysfunctions have revealed connections between patterns of cognitive dysfunction and specific profiles of memory impairment. The amnesic type of memory impairment is defined by deficits in both free recall and recognition memory, whereas the dysexecutive memory impairment is characterized by retrieval deficits, i.e. a disproportional impairment in free recall relative to recognition memory. The present study tests whether classifications of psychiatric patients into recall impaired only (= RO group) and Recall and Recognition impaired (= RR group) correspond to the executive type and amnesic type of memory impairment. The alternative hypothesis is that the two groups merely differ in degree of neuropsychological and psychiatric disturbance. Forty-four subjects impaired on California Verbal Learning Test (CVLT) were selected from a larger database of 103 impaired and non-impaired subjects with schizophrenia or recurrent major depression. Subjects were classified into RO and RR groups and compared on measures of memory strategy (recency effect and interference on CVLT), overall neuropsychological function (Stroop Test and WAIS-R similarity) and psychiatric symptom load (positive and negative symptoms). Repeated measures ANOVA showed no effects of group, i.e. the RR group did not perform consistently below the RO group with regard to memory strategy, neuropsychological function or psychiatric symptom load. Two out of three analyses showed group x test interaction, supporting the dissociation of distinct executive and amnesic profiles among psychiatric patients. The RO group was more susceptible to interference but had better recency score than the RR group. The RO had higher negative symptoms while the RR group had higher positive symptoms.

  17. No effect of odor-induced memory reactivation during REM sleep on declarative memory stability

    Directory of Open Access Journals (Sweden)

    Maren Jasmin Cordi

    2014-09-01

    Full Text Available Memory reactivations in hippocampal brain areas are critically involved in memory consolidation processes during sleep. In particular, specific firing patterns of hippocampal place cells observed during learning are replayed during subsequent sleep and rest in rodents. In humans, experimentally inducing hippocampal memory reactivations during slow-wave sleep (but not during wakefulness benefits consolidation and immediately stabilizes declarative memories against future interference. Importantly, spontaneous hippocampal replay activity can also be observed during rapid-eye movement (REM sleep and some authors have suggested that replay during REM sleep is related to processes of memory consolidation. However, the functional role of reactivations during REM sleep for memory stability is still unclear. Here, we reactivated memories during REM sleep and examined its consequences for the stability of declarative memories. After three hours of early, slow-wave sleep (SWS rich sleep, 16 healthy young adults learned a 2-D object location task in the presence of a contextual odor. During subsequent REM sleep, participants were either re-exposed to the odor or to an odorless vehicle, in a counterbalanced within subject design. Reactivation was followed by an interference learning task to probe memory stability after awakening. We show that odor-induced memory reactivation during REM sleep does not stabilize memories against future interference. We propose that the beneficial effect of reactivation during sleep on memory stability might be critically linked to processes characterizing SWS including, e.g., slow oscillatory activity, sleep spindles or low cholinergic tone, which are required for a successful redistribution of memories from medial temporal lobe regions to neocortical long-term stores.

  18. Galantamine improves apomorphine-induced deficits in prepulse inhibition via muscarinic ACh receptors in mice.

    Science.gov (United States)

    Yano, K; Koda, K; Ago, Y; Kobayashi, H; Kawasaki, T; Takuma, K; Matsuda, T

    2009-01-01

    Galantamine, a weak acetylcholine esterase (AChE) inhibitor and allosteric potentiator of nicotinic ACh receptors (nAChRs), improves apomorphine-induced deficits in prepulse inhibition (PPI), sensory information-processing deficits, via a nAChR-independent mechanism. The present study examined the role of muscarinic ACh receptors (mAChRs) in the effect of galantamine, and studied the mechanism of galantamine-induced increases in prefrontal ACh levels in mice. Apomorphine (1 mg kg(-1)) was administered to male ddY mice (9-10 weeks old) to create a PPI deficit model. Extracellular ACh concentrations in the prefrontal cortex were measured by in vivo microdialysis. Galantamine- and donepezil-mediated improvements in apomorphine-induced PPI deficits were blocked by the preferential M(1) mAChR antagonist telenzepine. The mAChR agonist oxotremorine also improved apomorphine-induced PPI deficits. Galantamine, like donepezil, increased extracellular ACh concentrations in the prefrontal cortex. Galantamine-induced increases in prefrontal ACh levels were partially blocked by the dopamine D(1) receptor antagonist SCH23390, but not by antagonists of mAChRs (telenzepine) and nAChRs (mecamylamine). Galantamine increased dopamine, but not 5-HT, release in the prefrontal cortex. Galantamine improves apomorphine-induced PPI deficits by stimulating mAChRs through increasing brain ACh levels via a dopamine D(1) receptor-dependent mechanism and AChE inhibition.

  19. Proactive interference and concurrent inhibitory processes do not differentially affect item and associative recognition: Implication for the age-related associative memory deficit.

    Science.gov (United States)

    Guez, Jonathan; Naveh-Benjamin, Moshe

    2016-09-01

    Previous studies have suggested an associative deficit hypothesis [Naveh-Benjamin, M. ( 2000 ). Adult age differences in memory performance: Tests of an associative deficit hypothesis. Journal of Experimental Psychology: Learning, Memory, and Cognition, 26, 1170-1187] to explain age-related episodic memory declines. The hypothesis attributes part of the deficient episodic memory performance in older adults to a difficulty in creating and retrieving cohesive episodes. In this article, we further evaluate this hypothesis by testing two alternative processes that potentially mediate associative memory deficits in older adults. Four experiments are presented that assess whether failure of inhibitory processes (proactive interference in Experiments 1 and 2), and concurrent inhibition (in Experiments 3 and 4) are mediating factors in age-related associative deficits. The results suggest that creating conditions that require the operation of inhibitory processes, or that interfere with such processes, cannot simulate associative memory deficit in older adults. Instead, such results support the idea that associative memory deficits reflect a unique binding failure in older adults. This failure seems to be independent of other cognitive processes, including inhibitory and other resource-demanding processes.

  20. Neural correlates of working memory deficits in schizophrenic patients. Ways to establish neurocognitive endophenotypes of psychiatric disorders

    International Nuclear Information System (INIS)

    Gruber, O.; Gruber, E.; Falkai, P.

    2005-01-01

    This article briefly reviews some methodological limitations of functional neuroimaging studies in psychiatric patients. We argue that the investigation of the neural substrates of cognitive deficits in psychiatric disorders requires a combination of functional neuroimaging studies in healthy subjects with corresponding behavioral experiments in patients. In order to exemplify this methodological approach we review recent findings regarding the functional neuroanatomy of distinct components of human working memory and provide evidence for selective dysfunctions of cortical networks that underlie specific working memory deficits in schizophrenia. This identification of subgroups of schizophrenic patients according to neurocognitive parameters may facilitate the establishment of behavioral and neurophysiological endophenotypes and the development of a neurobiological classification of psychiatric disorders. (orig.) [de

  1. Whole brain radiation-induced impairments in learning and memory are time-sensitive and reversible by systemic hypoxia.

    Science.gov (United States)

    Warrington, Junie P; Csiszar, Anna; Mitschelen, Matthew; Lee, Yong Woo; Sonntag, William E

    2012-01-01

    Whole brain radiation therapy (WBRT) is commonly used for treatment of primary and metastatic brain tumors; however, cognitive impairment occurs in 40-50% of brain tumor survivors. The etiology of the cognitive impairment following WBRT remains elusive. We recently reported that radiation-induced cerebrovascular rarefaction within hippocampal subregions could be completely reversed by systemic hypoxia. However, the effects of this intervention on learning and memory have not been reported. In this study, we assessed the time-course for WBRT-induced impairments in contextual and spatial learning and the capacity of systemic hypoxia to reverse WBRT-induced deficits in spatial memory. A clinical fractionated series of 4.5Gy WBRT was administered to mice twice weekly for 4 weeks, and after various periods of recovery, behavioral analyses were performed. To study the effects of systemic hypoxia, mice were subjected to 11% (hypoxia) or 21% oxygen (normoxia) for 28 days, initiated 1 month after the completion of WBRT. Our results indicate that WBRT induces a transient deficit in contextual learning, disruption of working memory, and progressive impairment of spatial learning. Additionally, systemic hypoxia completely reversed WBRT-induced impairments in learning and these behavioral effects as well as increased vessel density persisted for at least 2 months following hypoxia treatment. Our results provide critical support for the hypothesis that cerebrovascular rarefaction is a key component of cognitive impairment post-WBRT and indicate that processes of learning and memory, once thought to be permanently impaired after WBRT, can be restored.

  2. Functional neuroimaging of visuospatial working memory tasks enables accurate detection of attention deficit and hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Rubi Hammer

    2015-01-01

    Full Text Available Finding neurobiological markers for neurodevelopmental disorders, such as attention deficit and hyperactivity disorder (ADHD, is a major objective of clinicians and neuroscientists. We examined if functional Magnetic Resonance Imaging (fMRI data from a few distinct visuospatial working memory (VSWM tasks enables accurately detecting cases with ADHD. We tested 20 boys with ADHD combined type and 20 typically developed (TD boys in four VSWM tasks that differed in feedback availability (feedback, no-feedback and reward size (large, small. We used a multimodal analysis based on brain activity in 16 regions of interest, significantly activated or deactivated in the four VSWM tasks (based on the entire participants' sample. Dimensionality of the data was reduced into 10 principal components that were used as the input variables to a logistic regression classifier. fMRI data from the four VSWM tasks enabled a classification accuracy of 92.5%, with high predicted ADHD probability values for most clinical cases, and low predicted ADHD probabilities for most TDs. This accuracy level was higher than those achieved by using the fMRI data of any single task, or the respective behavioral data. This indicates that task-based fMRI data acquired while participants perform a few distinct VSWM tasks enables improved detection of clinical cases.

  3. Anxiety modulates the relation between attention-deficit/hyperactivity disorder severity and working memory-related brain activity.

    Science.gov (United States)

    van der Meer, Dennis; Hoekstra, Pieter J; van Rooij, Daan; Winkler, Anderson M; van Ewijk, Hanneke; Heslenfeld, Dirk J; Oosterlaan, Jaap; Faraone, Stephen V; Franke, Barbara; Buitelaar, Jan K; Hartman, Catharina A

    2017-03-01

    Individuals with attention-deficit/hyperactivity disorder (ADHD) often have heightened levels of anxiety, which has been associated with worse performance on working memory tasks. Knowledge of the neural pathways underlying the combined presence of ADHD and anxiety may aid in a better understanding of their co-occurrence. Therefore, we investigated how anxiety modulates the effect of ADHD severity on neural activity during a visuospatial working memory (VSWM) task. Neuroimaging data were available for 371 adolescents and young adults participating in the multicentre cohort study NeuroIMAGE (average age 17.1 years). We analysed the effects of ADHD severity, anxiety severity and their interaction on-task accuracy, and on neural activity associated with working memory (VSWM trials minus baseline), and memory load (high memory load trials minus low load trials). Anxiety significantly modulated the relation between ADHD severity and neural activity in the cerebellum for the working memory contrast, and bilaterally in the striatum and thalamus for the memory load contrast. We found that ADHD with co-occurring anxiety is associated with lowered neural activity during a VSWM task in regions important for information gating. This fits well with previous theorising on ADHD with co-occurring anxiety, and illustrates the neurobiological heterogeneity of ADHD.

  4. Attention-deficit/hyperactivity disorder: the impact of methylphenidate on working memory, inhibition capacity and mental flexibility

    OpenAIRE

    Bolfer, Cristiana; Pacheco, Sandra Pasquali; Tsunemi, Miriam Harumi; Carreira, Walter Souza; Casella, Beatriz Borba; Casella, Erasmo Barbante

    2017-01-01

    ABSTRACT Objective To compare children with attention-deficit/hyperactivity disorder (ADHD), before and after the use of methylphenidate, and a control group, using tests of working memory, inhibition capacity and mental flexibility. Methods Neuropsychological tests were administrated to 53 boys, 9–12 years old: the WISC-III digit span backward, and arithmetic; Stroop Color; and Trail Making Tests. The case group included 23 boys with ADHD, who were combined type, treatment-naive, and wit...

  5. Chemical memory reactions induced bursting dynamics in gene expression.

    Science.gov (United States)

    Tian, Tianhai

    2013-01-01

    Memory is a ubiquitous phenomenon in biological systems in which the present system state is not entirely determined by the current conditions but also depends on the time evolutionary path of the system. Specifically, many memorial phenomena are characterized by chemical memory reactions that may fire under particular system conditions. These conditional chemical reactions contradict to the extant stochastic approaches for modeling chemical kinetics and have increasingly posed significant challenges to mathematical modeling and computer simulation. To tackle the challenge, I proposed a novel theory consisting of the memory chemical master equations and memory stochastic simulation algorithm. A stochastic model for single-gene expression was proposed to illustrate the key function of memory reactions in inducing bursting dynamics of gene expression that has been observed in experiments recently. The importance of memory reactions has been further validated by the stochastic model of the p53-MDM2 core module. Simulations showed that memory reactions is a major mechanism for realizing both sustained oscillations of p53 protein numbers in single cells and damped oscillations over a population of cells. These successful applications of the memory modeling framework suggested that this innovative theory is an effective and powerful tool to study memory process and conditional chemical reactions in a wide range of complex biological systems.

  6. Executive Functions, Memory, and Social Cognitive Deficits and Recovery in Chronic Alcoholism: A Critical Review to Inform Future Research.

    Science.gov (United States)

    Le Berre, Anne-Pascale; Fama, Rosemary; Sullivan, Edith V

    2017-08-01

    Alcoholism is a complex and dynamic disease, punctuated by periods of abstinence and relapse, and influenced by a multitude of vulnerability factors. Chronic excessive alcohol consumption is associated with cognitive deficits, ranging from mild to severe, in executive functions, memory, and metacognitive abilities, with associated impairment in emotional processes and social cognition. These deficits can compromise efforts in initiating and sustaining abstinence by hampering efficacy of clinical treatment and can obstruct efforts in enabling good decision making success in interpersonal/social interactions, and awareness of cognitive and behavioral dysfunctions. Despite evidence for differences in recovery levels of selective cognitive processes, certain deficits can persist even with prolonged sobriety. Herein is presented a review of alcohol-related cognitive impairments affecting component processes of executive functioning, memory, and the recently investigated cognitive domains of metamemory, social cognition, and emotional processing; also considered are trajectories of cognitive recovery with abstinence. Finally, in the spirit of critical review, limitations of current knowledge are noted and avenues for new research efforts are proposed that focus on (i) the interaction among emotion-cognition processes and identification of vulnerability factors contributing to the development of emotional and social processing deficits and (ii) the time line of cognitive recovery by tracking alcoholism's dynamic course of sobriety and relapse. Knowledge about the heterochronicity of cognitive recovery in alcoholism has the potential of indicating at which points during recovery intervention may be most beneficial. Copyright © 2017 by the Research Society on Alcoholism.

  7. Age-related top-down suppression deficit in the early stages of cortical visual memory processing.

    Science.gov (United States)

    Gazzaley, Adam; Clapp, Wesley; Kelley, Jon; McEvoy, Kevin; Knight, Robert T; D'Esposito, Mark

    2008-09-02

    In this study, electroencephalography (EEG) was used to examine the relationship between two leading hypotheses of cognitive aging, the inhibitory deficit and the processing speed hypothesis. We show that older adults exhibit a selective deficit in suppressing task-irrelevant information during visual working memory encoding, but only in the early stages of visual processing. Thus, the employment of suppressive mechanisms are not abolished with aging but rather delayed in time, revealing a decline in processing speed that is selective for the inhibition of irrelevant information. EEG spectral analysis of signals from frontal regions suggests that this results from excessive attention to distracting information early in the time course of viewing irrelevant stimuli. Subdividing the older population based on working memory performance revealed that impaired suppression of distracting information early in the visual processing stream is associated with poorer memory of task-relevant information. Thus, these data reconcile two cognitive aging hypotheses by revealing that an interaction of deficits in inhibition and processing speed contributes to age-related cognitive impairment.

  8. Persistent deficits in hippocampal synaptic plasticity accompany losses of hippocampus-dependent memory in a rodent model of psychosis

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    Valentina eWiescholleck

    2013-03-01

    Full Text Available Irreversible N-methyl-D-aspartate receptor (NMDAR antagonism is known to provoke symptoms of psychosis and schizophrenia in healthy humans. NMDAR hypofunction is believed to play a central role in the pathophysiology of both disorders and in an animal model of psychosis, that is based on irreversible antagonism of NMDARs, pronounced deficits in hippocampal synaptic plasticity have been reported shortly after antagonist treatment. Here, we examined the long-term consequences for long-term potentiation (LTP of a single acute treatment with an irreversible antagonist and investigated whether deficits are associated with memory impairments.The ability to express long-term potentiation (LTP at the perforant pathway – dentate gyrus synapse, as well as object recognition memory was assessed 1, 2, 3 and 4 weeks after a single -treatment of the antagonist, MK801. Here, LTP in freely behaving rats was significantly impaired at all time-points compared to control LTP before treatment. Object recognition memory was also significantly poorer in MK801-treated compared to vehicle-treated animals for several weeks after treatment. Histological analysis revealed no changes in brain tissue.Taken together, these data support that acute treatment with an irreversible NMDAR antagonist persistently impairs hippocampal functioning on behavioral, as well as synaptic levels. The long-term deficits in synaptic plasticity may underlie the cognitive impairments that are associated with schizophrenia-spectrum disorders.

  9. Combined mnemonic strategy training and high-definition transcranial direct current stimulation for memory deficits in mild cognitive impairment.

    Science.gov (United States)

    Hampstead, Benjamin M; Sathian, Krishnankutty; Bikson, Marom; Stringer, Anthony Y

    2017-09-01

    Memory deficits characterize Alzheimer's dementia and the clinical precursor stage known as mild cognitive impairment. Nonpharmacologic interventions hold promise for enhancing functioning in these patients, potentially delaying functional impairment that denotes transition to dementia. Previous findings revealed that mnemonic strategy training (MST) enhances long-term retention of trained stimuli and is accompanied by increased blood oxygen level-dependent signal in the lateral frontal and parietal cortices as well as in the hippocampus. The present study was designed to enhance MST generalization, and the range of patients who benefit, via concurrent delivery of transcranial direct current stimulation (tDCS). This protocol describes a prospective, randomized controlled, four-arm, double-blind study targeting memory deficits in those with mild cognitive impairment. Once randomized, participants complete five consecutive daily sessions in which they receive either active or sham high definition tDCS over the left lateral prefrontal cortex, a region known to be important for successful memory encoding and that has been engaged by MST. High definition tDCS (active or sham) will be combined with either MST or autobiographical memory recall (comparable to reminiscence therapy). Participants undergo memory testing using ecologically relevant measures and functional magnetic resonance imaging before and after these treatment sessions as well as at a 3-month follow-up. Primary outcome measures include face-name and object-location association tasks. Secondary outcome measures include self-report of memory abilities as well as a spatial navigation task (near transfer) and prose memory (medication instructions; far transfer). Changes in functional magnetic resonance imaging will be evaluated during both task performance and the resting-state using activation and connectivity analyses. The results will provide important information about the efficacy of cognitive and

  10. Efficacy of Medication and Nonmedication Methods on Working Memory of Children With Attention Deficit and Hyperactivity Disorder

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    Ahmadpanah

    2015-05-01

    Full Text Available Background Working memory is the ability to keep and manipulate information in a short time. Children with attention deficit and hyperactivity disorder (ADHD are among the people suffering from deficiency in the active memory, and this deficiency has been attributed to the problem of frontal lobe. This study utilized a new approach with suitable tasks and methods for training active memory and assessment of its effects. Objectives This study aimed to investigate the effectiveness of medicinal and behavioral therapies on working memory of children with attention deficit and hyperactivity disorder. Patients and Methods The children participating in this study were 7 - 15 years old, and were diagnosed with ADHD by the psychiatrist and psychologist based on DSM-IV criteria. The intervention group comprised 8 boys and 6 girls with the average age of 11 (± 2 years, and the control group comprised 2 girls and 5 boys with an average age of 11.4 (± 3. Three children in the test group and 2 in the control group were under medicinal therapy. Results Training of working memory significantly improved the performance in nontrained areas as visual-spatial working memory as well as the performance in Raven progressive tests which are a perfect example of nonverbal, complicated reasoning tasks. Conclusions The performance of working memory improved through training, and these trainings extended to other areas of cognition functions not receiving any training. Trainings resulted in the improvement of performance in the tasks related to prefrontal area. They had also a positive and significant impact on the movement activities of hyperactive children.

  11. Memory deficits in amyotrophic lateral sclerosis are not exclusively caused by executive dysfunction: a comparative neuropsychological study of amnestic mild cognitive impairment

    OpenAIRE

    Machts, Judith; Bittner, Verena; Kasper, Elisabeth; Schuster, Christina; Prudlo, Johannes; Abdulla, Susanne; Kollewe, Katja; Petri, Susanne; Dengler, Reinhard; Heinze, Hans-Jochen; Vielhaber, Stefan; Schoenfeld, Mircea A; Bittner, Daniel M

    2014-01-01

    Background Recent work suggests that ALS and frontotemporal dementia can occur together and share at least in part the same underlying pathophysiology. However, it is unclear at present whether memory deficits in ALS stem from a temporal lobe dysfunction, or are rather driven by frontal executive dysfunction. In this study we sought to investigate the nature of memory deficits by analyzing the neuropsychological performance of 40 ALS patients in comparison to 39 amnestic mild cognitive impair...

  12. Inactivation of basolateral amygdala prevents chronic immobilization stress-induced memory impairment and associated changes in corticosterone levels.

    Science.gov (United States)

    Tripathi, Sunil Jamuna; Chakraborty, Suwarna; Srikumar, B N; Raju, T R; Shankaranarayana Rao, B S

    2017-07-01

    Chronic stress causes detrimental effects on various forms of learning and memory. The basolateral amygdala (BLA) not only plays a crucial role in mediating certain forms of memory, but also in the modulation of the effects of stress. Chronic immobilization stress (CIS) results in hypertrophy of the BLA, which is believed to be one of the underlying causes for stress' effects on learning. Thus, it is plausible that preventing the effects of CIS on amygdala would preclude its deleterious cognitive effects. Accordingly, in the first part, we evaluated the effect of excitotoxic lesion of the BLA on chronic stress-induced hippocampal-dependent spatial learning using a partially baited radial arm maze task. The BLA was ablated bilaterally using ibotenic acid prior to CIS. Chronically stressed rats showed impairment in spatial learning with decreased percentage correct choice and increased reference memory errors. Excitotoxic lesion of the BLA prevented the impairment in spatial learning and reference memory. In the retention test, lesion of the BLA was able to rescue the chronic stress-induced impairment. Interestingly, stress-induced enhanced plasma corticosterone levels were partially prevented by the lesion of BLA. These results motivated us to evaluate if the same effects can be observed with temporary inactivation of BLA, only during stress. We found that chronic stress-induced spatial learning deficits were also prevented by temporary inactivation of the BLA. Additionally, temporary inactivation of BLA partially precluded the stress-induced increase in plasma corticosterone levels. Thus, inactivation of BLA precludes stress-induced spatial learning deficits, and enhanced plasma corticosterone levels. It is speculated that BLA inactivation-induced reduction in corticosterone levels during stress, might be crucial in restoring spatial learning impairments. Our study provides evidence that amygdalar modulation during stress might be beneficial for strategic

  13. A Meta-Analysis of Working Memory Deficits in Children with Learning Difficulties: Is There a Difference between Verbal Domain and Numerical Domain?

    Science.gov (United States)

    Peng, Peng; Fuchs, Douglas

    2016-01-01

    Children with learning difficulties suffer from working memory (WM) deficits. Yet the specificity of deficits associated with different types of learning difficulties remains unclear. Further research can contribute to our understanding of the nature of WM and the relationship between it and learning difficulties. The current meta-analysis…

  14. Working Memory Arrest in Children with High-Functioning Autism Compared to Children with Attention-Deficit/Hyperactivity Disorder: Results from a 2-Year Longitudinal Study

    Science.gov (United States)

    Andersen, Per N.; Skogli, Erik W.; Hovik, Kjell T.; Geurts, Hilde; Egeland, Jens; Øie, Merete

    2015-01-01

    The aim of this study was to analyse the development of verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. A total of 34 children with high-functioning autism, 72 children with attention-deficit/hyperactivity disorder and 45 typically…

  15. Improving Working Memory in Children with Attention-Deficit/Hyperactivity Disorder: The Separate and Combined Effects of Incentives and Stimulant Medication

    Science.gov (United States)

    Strand, Michael T.; Hawk, Larry W., Jr.; Bubnik, Michelle; Shiels, Keri; Pelham, William E., Jr.; Waxmonsky, James G.

    2012-01-01

    Working memory (WM) is considered a core deficit in Attention-Deficit/Hyperactivity Disorder (ADHD), with numerous studies demonstrating impaired WM among children with ADHD. We tested the degree to which WM in children with ADHD was improved by performance-based incentives, an analog of behavioral intervention. In two studies, WM performance was…

  16. A Characterization of Visual, Semantic and Auditory Memory in Children with Combination-Type Attention Deficit, Primarily Inattentive, and a Control Group

    Science.gov (United States)

    Ramirez, Luz Angela; Arenas, Angela Maria; Henao, Gloria Cecilia

    2005-01-01

    Introduction: This investigation describes and compares characteristics of visual, semantic and auditory memory in a group of children diagnosed with combined-type attention deficit with hyperactivity, attention deficit predominating, and a control group. Method: 107 boys and girls were selected, from 7 to 11 years of age, all residents in the…

  17. Three dopamine pathways induce aversive odor memories with different stability.

    Directory of Open Access Journals (Sweden)

    Yoshinori Aso

    Full Text Available Animals acquire predictive values of sensory stimuli through reinforcement. In the brain of Drosophila melanogaster, activation of two types of dopamine neurons in the PAM and PPL1 clusters has been shown to induce aversive odor memory. Here, we identified the third cell type and characterized aversive memories induced by these dopamine neurons. These three dopamine pathways all project to the mushroom body but terminate in the spatially segregated subdomains. To understand the functional difference of these dopamine pathways in electric shock reinforcement, we blocked each one of them during memory acquisition. We found that all three pathways partially contribute to electric shock memory. Notably, the memories mediated by these neurons differed in temporal stability. Furthermore, combinatorial activation of two of these pathways revealed significant interaction of individual memory components rather than their simple summation. These results cast light on a cellular mechanism by which a noxious event induces different dopamine signals to a single brain structure to synthesize an aversive memory.

  18. Histone deacetylase inhibition abolishes stress-induced spatial memory impairment.

    Science.gov (United States)

    Vargas-López, Viviana; Lamprea, Marisol R; Múnera, Alejandro

    2016-10-01

    Acute stress induced before spatial training impairs memory consolidation. Although non-epigenetic underpinning of such effect has been described, the epigenetic mechanisms involved have not yet been studied. Since spatial training and intense stress have opposite effects on histone acetylation balance, it is conceivable that disruption of such balance may underlie acute stress-induced spatial memory consolidation impairment and that inhibiting histone deacetylases prevents such effect. Trichostatin-A (TSA, a histone deacetylase inhibitor) was used to test its effectiveness in preventing stress' deleterious effect on memory. Male Wistar rats were trained in a spatial task in the Barnes maze; 1-h movement restraint was applied to half of them before training. Immediately after training, stressed and non-stressed animals were randomly assigned to receive either TSA (1mg/kg) or vehicle intraperitoneal injection. Twenty-four hours after training, long-term spatial memory was tested; plasma and brain tissue were collected immediately after the memory test to evaluate corticosterone levels and histone H3 acetylation in several brain areas. Stressed animals receiving vehicle displayed memory impairment, increased plasma corticosterone levels and markedly reduced histone H3 acetylation in prelimbic cortex and hippocampus. Such effects did not occur in stressed animals treated with TSA. The aforementioned results support the hypothesis that acute stress induced-memory impairment is related to histone deacetylation. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Neonatal handling induces deficits in infant mother preference and adult partner preference.

    Science.gov (United States)

    Raineki, Charlis; Lutz, Maiara Lenise; Sebben, Vanise; Ribeiro, Rosane Aparecida; Lucion, Aldo Bolten

    2013-07-01

    Neonatal handling is an experimental procedure used to understand how early-life adversity can negatively affect neurobehavioral development and place animals on a pathway to pathology. Decreased preference for the maternal odor during infancy is one of many behavioral deficits induced by neonatal handling. Here, we hypothesize that deficits in maternal odor preference may interfere with partner preference in the adult. To test this hypothesis, we assessed infant maternal odor preference and adult partner preference in different reproductive stages in both male and female rats that received neonatal handling. Our results indicate that only neonatally handled females present deficits in maternal odor preference during infancy, but both male and females present deficits in adult partner preference. However, sexual experience was effective in rescuing partner preference deficits in males. These results indicate that, considering infant and adult social interactions, females are more susceptible to the effects of neonatal handling than males. Copyright © 2012 Wiley Periodicals, Inc.

  20. A neurodevelopmental approach to understanding memory processes among intellectually gifted youth with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Whitaker, Ashley M; Bell, Terece S; Houskamp, Beth M; O'Callaghan, Erin T

    2015-01-01

    Intellectual giftedness is associated with strong strategic verbal memory while attention-deficit hyperactivity disorder (ADHD) is associated with strategic verbal memory deficits; however, no previous research has explored how this contradiction manifests in gifted populations with diagnoses of ADHD. The purpose of this study was to explore strategic verbal memory processes among intellectually gifted youth with and without ADHD to provide clarification regarding this specific aspect of neuropsychological functioning within this population. One hundred twenty-five youth completed neuropsychological evaluations including the Wechsler Intelligence Scale for Children-Fourth Edition and California Verbal Learning Test-Children's Version (CVLT-C). Results revealed significant differences between groups, with intellectually gifted youth with ADHD achieving lower T scores on CVLT-C Trials 1 through 5 compared with intellectually gifted youth without ADHD, and intellectually gifted youth with ADHD achieving higher T scores than youth of average intellectual abilities with ADHD. Additionally, repeated-measures analysis of variance revealed a main effect improvement among gifted youth with ADHD in short-delay recall when provided with organizational cues. Findings revealed new evidence about the role of twice exceptionality (specifically intellectual giftedness and ADHD) in strategic verbal memory and have important implications for parents, educators, psychologists and neuropsychologists, and other mental health professionals working with this population.

  1. Fornix As An Imaging Marker For Episodic Memory Deficits In Healthy Aging and in Various Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Vanessa eDouet

    2015-01-01

    Full Text Available The fornix is a part of the limbic system and constitutes the major efferent and afferent white matter tracts from the hippocampi. The underdevelopment of or injuries to the fornix are strongly associated with memory deficits. Its role in memory impairments was suggested long ago with cases of surgical forniceal transaction. However, recent advances in brain imaging techniques, such as diffusion tensor imaging; enabling more qualitative and quantitative studies, have revealed that macrostructural and microstructural abnormalities of the fornix correlated highly with declarative and episodic memory performance. This structure appears to provide a robust and early imaging predictor for memory deficits not only in neurodegenerative and neuroinflammatory diseases, such as Alzheimer’s disease and multiple sclerosis, but also in schizophrenia and psychiatric disorders, and during neurodevelopment and typical aging. The objective of the manuscript is to present a systematic review regarding published brain imaging research on the fornix, including the development of its tracts, its role in various neurological diseases, and its relationship to neurocognitive performance in human studies.

  2. Fornix as an imaging marker for episodic memory deficits in healthy aging and in various neurological disorders

    Science.gov (United States)

    Douet, Vanessa; Chang, Linda

    2015-01-01

    The fornix is a part of the limbic system and constitutes the major efferent and afferent white matter tracts from the hippocampi. The underdevelopment of or injuries to the fornix are strongly associated with memory deficits. Its role in memory impairments was suggested long ago with cases of surgical forniceal transections. However, recent advances in brain imaging techniques, such as diffusion tensor imaging, have revealed that macrostructural and microstructural abnormalities of the fornix correlated highly with declarative and episodic memory performance. This structure appears to provide a robust and early imaging predictor for memory deficits not only in neurodegenerative and neuroinflammatory diseases, such as Alzheimer's disease and multiple sclerosis, but also in schizophrenia and psychiatric disorders, and during neurodevelopment and “typical” aging. The objective of the manuscript is to present a systematic review regarding published brain imaging research on the fornix, including the development of its tracts, its role in various neurological diseases, and its relationship to neurocognitive performance in human studies. PMID:25642186

  3. Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є4.

    Science.gov (United States)

    Olofsson, Jonas K; Josefsson, Maria; Ekström, Ingrid; Wilson, Donald; Nyberg, Lars; Nordin, Steven; Nordin Adolfsson, Annelie; Adolfsson, Rolf; Nilsson, Lars-Göran; Larsson, Maria

    2016-05-01

    The ɛ4 allele of the Apolipoprotein E gene is a genetic risk factor for late-onset dementia of the Alzheimers' type (DAT), which is characterized by loss of both episodic memory and olfactory functions. Little is known about the possible role of ɛ4 in the association between ongoing episodic memory decline and olfactory deficits in the general population, but such information is relevant in determining the relevance of olfaction as a marker of DAT risk. The present study was based on a large, population-based sample (n=1087, aged 45-90 years, of which 324 were ɛ4-carriers). Episodic memory change rates were established using data collected every 5 years for a 10-20 year interval leading up to an olfactory assessment using the Scandinavian Odor Identification Test at the last wave of data collection. Participants were classified according to whether or not their episodic memory ability declined more rapidly than the age-typical norm (by >1SD). Our main result is that only in ɛ4-carriers was episodic memory decline associated with odor identification impairment. In individuals without ɛ4, odor identification was unrelated to episodic memory decline status. Follow-up analyses indicated that this moderation by ɛ4 was due to the olfactory nature of the identification test, and that the effect was not caused by 63 individuals with dementia. Our results suggest that the ɛ4 determines the functional association between ongoing episodic memory decline and olfaction. These findings are consistent with the notion that ɛ4-carriers with DAT, compared to non-carriers, display a cortical atrophy pattern that is more focused on mediotemporal lobe regions supporting olfactory and episodic memory functions. Olfactory and memory assessments might provide complementary information on mediotemporal atrophy prior to clinical dementia onset, but the ɛ4 should be considered when using olfactory assessment as an early-stage indicator. Copyright © 2016. Published by Elsevier Ltd.

  4. [Gly14]-Humanin improved the learning and memory impairment induced by scopolamine in vivo

    Science.gov (United States)

    Mamiya, Takayoshi; Ukai, Makoto

    2001-01-01

    Humanin is a very recently discovered 24 amino acid linear polypeptide, which protects against cell death induced by either familial Alzheimer's disease mutant of amyloid precursor protein, presenilin-1 or presenilin-2 in vitro. However, it has remained uncertain whether humanin is a useful drug for the animal model of learning and memory deficit. In this study, we evaluated the effects of [Gly14]-humanin, a more potent humanin analogue, on the scopolamine HBr (1 mg kg−1 s.c.)-induced impairment of spontaneous alternation behaviour in the Y-maze, an index of short-term memory in mice. [Gly14]-Humanin (1000 pmol 5 μl−1 i.c.v.) reversed the impairment without affecting the number of arm entries. These results suggest that (I) [Gly14]-humanin is a beneficial drug for the impairment of learning and memory and (II) it modulates the learning and memory function mediated via cholinergic systems in mice. PMID:11739234

  5. Protective Effect of Vitamin E Against Lead-induced Memory and Learning Impairment in Male Rats

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    Salehi

    2015-02-01

    Full Text Available Background Lead (Pb2+ is a neurotoxin substance that has been known for its adverse effects on central nervous system and memory. Previous studies reported the potential effect of vitamin E as a memory enhancer. Objectives The purpose of the present study was to assess the protective effects of vitamin E against Pb-induced amnesia. Materials and Methods Forty-eight male Wistar rats (200-250 g were divided equally into the saline, Pb, Pb + vitamin E, and vitamin E alone groups. To induce Pb toxicity, rats received water that contained 0.2% Pb instead of regular water for 1 month. Rats pretreated, treated or post treated with vitamin E (150 mg/kg for 2 months. Passive avoidance learning was assessed using Shuttle-Box after two months. Retention was tested 24 and 48 hours after training. Results The results showed that Pb caused impairment in acquisition and retrieval processes in passive avoidance learning. Vitamin E reversed learning and memory deficits in pre, post or co- exposure with Pb (P < 0.001. Conclusions According to the results of this study, administration of vitamin E to rats counteracts the negative effects of Pb on learning and memory. To more precisely extrapolate these findings to humans, future clinical studies are warranted.

  6. Deficits in verbal long-term memory and learning in children with poor phonological short-term memory skills.

    Science.gov (United States)

    Gathercole, Susan E; Briscoe, Josie; Thorn, Annabel; Tiffany, Claire

    2008-03-01

    Possible links between phonological short-term memory and both longer term memory and learning in 8-year-old children were investigated in this study. Performance on a range of tests of long-term memory and learning was compared for a group of 16 children with poor phonological short-term memory skills and a comparison group of children of the same age with matched nonverbal reasoning abilities but memory scores in the average range. The low-phonological-memory group were impaired on longer term memory and learning tasks that taxed memory for arbitrary verbal material such as names and nonwords. However, the two groups performed at comparable levels on tasks requiring the retention of visuo-spatial information and of meaningful material and at carrying out prospective memory tasks in which the children were asked to carry out actions at a future point in time. The results are consistent with the view that poor short-term memory function impairs the longer-term retention and ease of learning of novel verbal material.

  7. Understanding phonological memory deficits in boys with attention-deficit/hyperactivity disorder (ADHD): dissociation of short-term storage and articulatory rehearsal processes.

    Science.gov (United States)

    Bolden, Jennifer; Rapport, Mark D; Raiker, Joseph S; Sarver, Dustin E; Kofler, Michael J

    2012-08-01

    The current study dissociated and examined the two primary components of the phonological working memory subsystem--the short-term store and articulatory rehearsal mechanism--in boys with ADHD (n = 18) relative to typically developing boys (n = 15). Word lists of increasing length (2, 4, and 6 words per trial) were presented to and recalled by children following a brief (3 s) interval to assess their phonological short-term storage capacity. Children's ability to utilize the articulatory rehearsal mechanism to actively maintain information in the phonological short-term store was assessed using word lists at their established memory span but with extended rehearsal times (12 s and 21 s delays). Results indicate that both phonological shortterm storage capacity and articulatory rehearsal are impaired or underdeveloped to a significant extent in boys with ADHD relative to typically developing boys, even after controlling for age, SES, IQ, and reading speed. Larger magnitude deficits, however, were apparent in short-term storage capacity (ES = 1.15 to 1.98) relative to articulatory rehearsal (ES = 0.47 to 1.02). These findings are consistent with previous reports of deficient phonological short-term memory in boys with ADHD, and suggest that future attempts to develop remedial cognitive interventions for children with ADHD will need to include active components that require children to hold increasingly more information over longer time intervals.

  8. Inhibition of γ-secretase worsens memory deficits in a genetically congruous mouse model of Danish dementia

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    Tamayev Robert

    2012-04-01

    Full Text Available Abstract Background A mutation in the BRI2/ITM2b gene causes familial Danish dementia (FDD. BRI2 is an inhibitor of amyloid-β precursor protein (APP processing, which is genetically linked to Alzheimer’s disease (AD pathogenesis. The FDD mutation leads to a loss of BRI2 protein and to increased APP processing. APP haplodeficiency and inhibition of APP cleavage by β-secretase rescue synaptic/memory deficits of a genetically congruous mouse model of FDD (FDDKI. β-cleavage of APP yields the β-carboxyl-terminal (β-CTF and the amino-terminal-soluble APPβ (sAPPβ fragments. γ-secretase processing of β-CTF generates Aβ, which is considered the main cause of AD. However, inhibiting Aβ production did not rescue the deficits of FDDKI mice, suggesting that sAPPβ/β-CTF, and not Aβ, are the toxic species causing memory loss. Results Here, we have further analyzed the effect of γ-secretase inhibition. We show that treatment with a γ-secretase inhibitor (GSI results in a worsening of the memory deficits of FDDKI mice. This deleterious effect on memory correlates with increased levels of the β/α-CTFs APP fragments in synaptic fractions isolated from hippocampi of FDDKI mice, which is consistent with inhibition of γ-secretase activity. Conclusion This harmful effect of the GSI is in sharp contrast with a pathogenic role for Aβ, and suggests that the worsening of memory deficits may be due to accumulation of synaptic-toxic β/α-CTFs caused by GSI treatment. However, γ-secretase cleaves more than 40 proteins; thus, the noxious effect of GSI on memory may be dependent on inhibition of cleavage of one or more of these other γ-secretase substrates. These two possibilities do not need to be mutually exclusive. Our results are consistent with the outcome of a clinical trial with the GSI Semagacestat, which caused a worsening of cognition, and advise against targeting γ-secretase in the therapy of AD. Overall, the data also indicate that FDDKI

  9. Terrestrial neutron-induced soft errors in advanced memory devices

    CERN Document Server

    Nakamura, Takashi; Ibe, Eishi; Yahagi, Yasuo; Kameyama, Hideaki

    2008-01-01

    Terrestrial neutron-induced soft errors in semiconductor memory devices are currently a major concern in reliability issues. Understanding the mechanism and quantifying soft-error rates are primarily crucial for the design and quality assurance of semiconductor memory devices. This book covers the relevant up-to-date topics in terrestrial neutron-induced soft errors, and aims to provide succinct knowledge on neutron-induced soft errors to the readers by presenting several valuable and unique features. Sample Chapter(s). Chapter 1: Introduction (238 KB). Table A.30 mentioned in Appendix A.6 on

  10. Cognitive Training and Work Therapy for the Treatment of Verbal Learning and Memory Deficits in Veterans With Alcohol Use Disorders.

    Science.gov (United States)

    Bell, Morris D; Vissicchio, Nicholas A; Weinstein, Andrea J

    2016-01-01

    This study focused on the efficacy of cognitive training for verbal learning and memory deficits in a population of older veterans with alcohol use disorders. Veterans with alcohol use disorders, who were in outpatient treatment at VA facilities and in early-phase recovery (N = 31), were randomized to receive a three-month trial of daily cognitive training plus work therapy (n = 15) or work therapy alone (n = 16), along with treatment as usual. Participants completed assessments at baseline and at three- and six-month follow-ups; the Hopkins Verbal Learning Task (HVLT) was the primary outcome measure. Participants were primarily male (97%) and in their mid-50s (M = 55.16, SD = 5.16) and had been sober for 1.64 (SD = 2.81) months. Study retention was excellent (91% at three-month follow-up) and adherence to treatment in both conditions was very good. On average, participants in the cognitive training condition had more than 41 hours of cognitive training, and both conditions had more than 230 hours of productive activity. HVLT results at three-month follow-up revealed significant condition effects favoring cognitive training for verbal learning (HVLT Trial-3 T-score, p cognitive training condition with clinically significant verbal memory deficits (p therapy alone condition and a trend toward significance for verbal learning deficits, which was not sustained at six-month follow-up. This National Institute on Drug Abuse-funded pilot study demonstrates that cognitive training within the context of another activating intervention (work therapy) may have efficacy in remediating verbal learning and memory deficits in patients with alcohol use disorder. Findings indicate a large effect for cognitive training in this pilot study, which suggests that further research is warranted. This study is registered on ClinicalTrials.gov (NCT 01410110).

  11. Associative memory and its cerebral correlates in Alzheimer's disease: Evidence for distinct deficits of relational and conjunctive memory

    OpenAIRE

    Bastin, Christine; Bahri, Mohamed Ali; Miévis, Frédéric; Lemaire, Christian; Collette, Fabienne; Genon, Sarah; Simon, Jessica; Guillaume, Bénédicte; Diana, Rachel A.; Yonelinas, Andrew P.; Salmon, Eric

    2014-01-01

    This study investigated the impact of Alzheimer's disease (AD) on conjunctive and relational binding in episodic memory. Mild AD patients and controls had to remember item-color associations by imagining color either as a contextual association (relational memory) or as a feature of the item to be encoded (conjunctive memory). Patients' performance in each condition was correlated with cerebral metabolism measured by FDG-PET. The results showed that AD patients had an impaired capacity to rem...

  12. NAAG peptidase inhibitors block cognitive deficit induced by MK-801 and motor activation induced by d-amphetamine in animal models of schizophrenia

    Science.gov (United States)

    Olszewski, R T; Janczura, K J; Ball, S R; Madore, J C; Lavin, K M; Lee, J C-M; Lee, M J; Der, E K; Hark, T J; Farago, P R; Profaci, C P; Bzdega, T; Neale, J H

    2012-01-01

    The most widely validated animal models of the positive, negative and cognitive symptoms of schizophrenia involve administration of d-amphetamine or the open channel NMDA receptor blockers, dizocilpine (MK-801), phencyclidine (PCP) and ketamine. The drug ZJ43 potently inhibits glutamate carboxypeptidase II (GCPII), an enzyme that inactivates the peptide transmitter N-acetylaspartylglutamate (NAAG) and reduces positive and negative behaviors induced by PCP in several of these models. NAAG is an agonist at the metabotropic glutamate receptor 3 (mGluR3). Polymorphisms in this receptor have been associated with expression of schizophrenia. This study aimed to determine whether two different NAAG peptidase inhibitors are effective in dopamine models, whether their efficacy was eliminated in GCPII knockout mice and whether the efficacy of these inhibitors extended to MK-801-induced cognitive deficits as assessed using the novel object recognition test. ZJ43 blocked motor activation when given before or after d-amphetamine treatment. (R,S)-2-phosphono-methylpentanedioic acid (2-PMPA), another potent NAAG peptidase inhibitor, also reduced motor activation induced by PCP or d-amphetamine. 2-PMPA was not effective in GCPII knockout mice. ZJ43 and 2-PMPA also blocked MK-801-induced deficits in novel object recognition when given before, but not after, the acquisition trial. The group II mGluR antagonist LY341495 blocked the effects of NAAG peptidase inhibition in these studies. 2-PMPA was more potent than ZJ43 in a test of NAAG peptidase inhibition in vivo. By bridging the dopamine and glutamate theories of schizophrenia with two structurally different NAAG peptidase inhibitors and demonstrating their efficacy in blocking MK-801-induced memory deficits, these data advance the concept that NAAG peptidase inhibition represents a potentially novel antipsychotic therapy. PMID:22850437

  13. Subclinical Doses of ATP-Sensitive Potassium Channel Modulators Prevent Alterations in Memory and Synaptic Plasticity Induced by Amyloid-β.

    Science.gov (United States)

    Salgado-Puga, Karla; Rodríguez-Colorado, Javier; Prado-Alcalá, Roberto A; Peña-Ortega, Fernando

    2017-01-01

    In addition to coupling cell metabolism and excitability, ATP-sensitive potassium channels (KATP) are involved in neural function and plasticity. Moreover, alterations in KATP activity and expression have been observed in Alzheimer's disease (AD) and during amyloid-β (Aβ)-induced pathology. Thus, we tested whether KATP modulators can influence Aβ-induced deleterious effects on memory, hippocampal network function, and plasticity. We found that treating animals with subclinical doses (those that did not change glycemia) of a KATP blocker (Tolbutamide) or a KATP opener (Diazoxide) differentially restrained Aβ-induced memory deficit, hippocampal network activity inhibition, and long-term synaptic plasticity unbalance (i.e., inhibition of LTP and promotion of LTD). We found that the protective effect of Tolbutamide against Aβ-induced memory deficit was strong and correlated with the reestablishment of synaptic plasticity balance, whereas Diazoxide treatment produced a mild protection against Aβ-induced memory deficit, which was not related to a complete reestablishment of synaptic plasticity balance. Interestingly, treatment with both KATP modulators renders the hippocampus resistant to Aβ-induced inhibition of hippocampal network activity. These findings indicate that KATP are involved in Aβ-induced pathology and they heighten the potential role of KATP modulation as a plausible therapeutic strategy against AD.

  14. Repeated Closed Head Injury in Mice Results in Sustained Motor and Memory Deficits and Chronic Cellular Changes.

    Directory of Open Access Journals (Sweden)

    Amanda N Bolton Hall

    Full Text Available Millions of mild traumatic brain injuries (TBIs occur every year in the United States, with many people subject to multiple head injuries that can lead to chronic behavioral dysfunction. We previously reported that mild TBI induced using closed head injuries (CHI repeated at 24h intervals produced more acute neuron death and glial reactivity than a single CHI, and increasing the length of time between injuries to 48h reduced the cumulative acute effects of repeated CHI. To determine whether repeated CHI is associated with behavioral dysfunction or persistent cellular damage, mice receiving either five CHI at 24h intervals, five CHI at 48h intervals, or five sham injuries at 24h intervals were evaluated across a 10 week period after injury. Animals with repeated CHI exhibited motor coordination and memory deficits, but not gait abnormalities when compared to sham animals. At 10wks post-injury, no notable neuron loss or glial reactivity was observed in the cortex, hippocampus, or corpus callosum. Argyrophilic axons were found in the pyramidal tract of some injured animals, but neither silver stain accumulation nor inflammatory responses in the injury groups were statistically different from the sham group in this region. However, argyrophilic axons, microgliosis and astrogliosis were significantly increased within the optic tract of injured animals. Repeated mild CHI also resulted in microgliosis and a loss of neurofilament protein 200 in the optic nerve. Lengthening the inter-injury interval from 24h to 48h did not effectively reduce these behavioral or cellular responses. These results suggest that repeated mild CHI results in persistent behavioral dysfunction and chronic pathological changes within the visual system, neither of which was significantly attenuated by lengthening the inter-injury interval from 24h to 48h.

  15. Transcranial direct current stimulation improves short-term memory in an animal model of attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Leffa, Douglas Teixeira; de Souza, Andressa; Scarabelot, Vanessa Leal; Medeiros, Liciane Fernandes; de Oliveira, Carla; Grevet, Eugenio Horacio; Caumo, Wolnei; de Souza, Diogo Onofre; Rohde, Luis Augusto Paim; Torres, Iraci L S

    2016-02-01

    Attention deficit hyperactivity disorder (ADHD) is characterized by impairing levels of hyperactivity, impulsivity and inattention. However, different meta-analyses have reported disruptions in short and long-term memory in ADHD patients. Previous studies indicate that mnemonic dysfunctions might be the result of deficits in attentional circuits, probably due to ineffective dopaminergic modulation of hippocampal synaptic plasticity. In this study we aimed to evaluate the potential therapeutic effects of a neuromodulatory technique, transcranial direct current stimulation (tDCS), in short-term memory (STM) deficits presented by the spontaneous hypertensive rats (SHR), the most widely used animal model of ADHD. Adult male SHR and Wistar Kyoto rats (WKY) were subjected to a constant electrical current of 0.5 mA intensity applied on the frontal cortex for 20 min/day during 8 days. STM was evaluated with an object recognition test conducted in an open field. Exploration time and locomotion were recorded, and brain regions were dissected to determine dopamine and BDNF levels. SHR spent less time exploring the new object when compared to WKY, and tDCS improved object recognition deficits in SHR without affecting WKY performance. Locomotor activity was higher in SHR and it was not affected by tDCS. After stimulation, dopamine levels were increased in the hippocampus and striatum of both strains, while BDNF levels were increased only in the striatum of WKY. These findings suggest that tDCS on the frontal cortex might be able to improve STM deficits present in SHR, which is potentially related to dopaminergic neurotransmission in the hippocampus and striatum of those animals. Copyright © 2016. Published by Elsevier B.V.

  16. Memory deficits in amyotrophic lateral sclerosis are not exclusively caused by executive dysfunction: a comparative neuropsychological study of amnestic mild cognitive impairment.

    Science.gov (United States)

    Machts, Judith; Bittner, Verena; Kasper, Elisabeth; Schuster, Christina; Prudlo, Johannes; Abdulla, Susanne; Kollewe, Katja; Petri, Susanne; Dengler, Reinhard; Heinze, Hans-Jochen; Vielhaber, Stefan; Schoenfeld, Mircea A; Bittner, Daniel M

    2014-06-30

    Recent work suggests that ALS and frontotemporal dementia can occur together and share at least in part the same underlying pathophysiology. However, it is unclear at present whether memory deficits in ALS stem from a temporal lobe dysfunction, or are rather driven by frontal executive dysfunction. In this study we sought to investigate the nature of memory deficits by analyzing the neuropsychological performance of 40 ALS patients in comparison to 39 amnestic mild cognitive impairment (aMCI) patients and 40 healthy controls (HC). The neuropsychological battery tested for impairment in executive functions, as well as memory and visuo-spatial skills, the results of which were compared across study groups. In addition, we calculated composite scores for memory (learning, recall, recognition) and executive functions (verbal fluency, cognitive flexibility, working memory). We hypothesized that the nature of memory impairment in ALS will be different from those exhibited by aMCI patients. Patient groups exhibited significant differences in their type of memory deficit, with the ALS group showing impairment only in recognition, whereas aMCI patients showed short and delayed recall performance deficits as well as reduced short-term capacity. Regression analysis revealed a significant impact of executive function on memory performance exclusively for the ALS group, accounting for one fifth of their memory performance. Interestingly, merging all sub scores into a single memory and an executive function score obscured these differences. The presented results indicate that the interpretation of neuropsychological scores needs to take the distinct cognitive profiles in ALS and aMCI into consideration. Importantly, the observed memory deficits in ALS were distinctly different from those observed in aMCI and can be explained only to some extent in the context of comorbid (coexisting) executive dysfunction. These findings highlight the qualitative differences in temporal lobe

  17. Memory plays tricks on me: perceptual bias induced by memory reactivated size in Ebbinghaus illusion.

    Science.gov (United States)

    Rey, Amandine E; Vallet, Guillaume T; Riou, Benoit; Lesourd, Mathieu; Versace, Rémy

    2015-10-01

    The relationship between perceptual and memory processing is at the core of cognition. Growing evidence suggests reciprocal influences between them so that memory features should lead to an actual perceptual bias. In the present study, we investigate the reciprocal influence of perceptual and memory processing by further adapting the Ebbinghaus illusion and tested it in a psychophysical design. In a 2AFC (two-alternative forced choice) paradigm, the perceptual bias in the Ebbinghaus illusion was induced by a physical size (Experiment 1) or a memory reactivated size of the inducers (Experiment 2, the size was reactivated thanks to a color-size association). One test disk was presented on the left of the screen and was surrounded by six inducers with a large or small (perceptual or reactivated) size. The test disk varied in size and participants were asked to indicate whether this test disk was smaller or larger than a reference disk presented on the right of the screen (the reference disk was invariant in size). Participants' responses were influenced by the size of the inducers for the perceptual and the reactivated size of the inducers. These results provide new evidence for the influence of memory on perception in a psychophysics paradigm. Published by Elsevier B.V.

  18. Amyloid β-mediated Zn2+ influx into dentate granule cells transiently induces a short-term cognitive deficit.

    Directory of Open Access Journals (Sweden)

    Atsushi Takeda

    Full Text Available We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ concentration. A single injection of Aβ (25 pmol into the dentate gyrus affected dentate gyrus long-term potentiation (LTP 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits.

  19. Stress-Induced Cortisol Hampers Memory Generalization

    Science.gov (United States)

    Dandolo, Lisa C.; Schwabe, Lars

    2016-01-01

    Integrative encoding and generalization across past experiences depends largely on the hippocampus, an area known to be particularly sensitive to stress. Yet, whether stress influences the ability to generalize memories is unknown. We exposed volunteers to a stressor or a control manipulation before they completed an acquired equivalence task…

  20. Lithium prevents REM sleep deprivation-induced impairments on memory consolidation.

    Science.gov (United States)

    Ota, Simone M; Moreira, Karin Di Monteiro; Suchecki, Deborah; Oliveira, Maria Gabriela M; Tiba, Paula A

    2013-11-01

    Pre-training rapid eye movement sleep (REMS) deprivation affects memory acquisition and/or consolidation. It also produces major REMS rebound at the cost of waking and slow wave sleep (SWS). Given that both SWS and REMS appear to be important for memory processes, REMS rebound after training may disrupt the organization of sleep cycles, i.e., excessive amount of REMS and/or little SWS after training could be harmful for memory formation. To examine whether lithium, a drug known to increase SWS and reduce REMS, could prevent the memory impairment induced by pre-training sleep deprivation. Animals were divided in 2 groups: cage control (CC) and REMS-deprived (REMSDep), and then subdivided into 4 subgroups, treated either with vehicle or 1 of 3 doses of lithium (50, 100, and 150 mg/kg) 2 h before training on the multiple trial inhibitory avoidance task. Animals were tested 48 h later to make sure that the drug had been already metabolized and eliminated. Another set of animals was implanted with electrodes and submitted to the same experimental protocol for assessment of drug-induced sleep-wake changes. Wistar male rats weighing 300-400 g. Sleep deprived rats required more trials to learn the task and still showed a performance deficit during test, except from those treated with 150 mg/kg of lithium, which also reduced the time spent in REM sleep during sleep recovery. Lithium reduced rapid eye movement sleep and prevented memory impairment induced by sleep deprivation. These results indicate that these phenomena may be related, but cause-effect relationship cannot be ascertained.

  1. Identification of peptides present in sour milk whey that ameliorate scopolamine-induced memory impairment in mice.

    Science.gov (United States)

    Ohsawa, Kazuhito; Uchida, Naoto; Ohki, Kohji; Yokogoshi, Hidehiko

    2018-02-01

    Cognitive impairment is treated with cholinesterase inhibitors that slow cognitive decline but cause significant adverse effects. Functional foods that improve memory without such effects would therefore be valuable. We reported that unidentified components of sour milk whey produced by fermentations using Lactobacillus helveticus and Saccharomyces cerevisiae improved memory in a mouse model of scopolamine-induced memory impairment. Here, we show that casein-derived peptides were the most active components of orally administered fractions of this milk product. Of five peptides tested, β-casein (residues 73-91) was the most effective for ameliorating scopolamine-induced cognitive deficits, as indicated by a significantly higher percentage of alternations of mice orally administered 0.05 nmol/kg peptide (58.0 ± 9.3%) versus vehicle (51.0 ± 5.8%). This orally active peptide may improve cognitive function of patients with dementia.

  2. Progesterone regulates corticosterone elevation and alterations in spatial memory and exploratory behavior induced by stress in Wistar rats

    Directory of Open Access Journals (Sweden)

    Yolanda Diaz-Burke

    2010-02-01

    Full Text Available The hippocampus is sensitive to high levels of glucocorticoids during stress responses; it suffers biochemical and cellular changes that affect spatial memory and exploratory behavior, among others. We analyzed the influence of the neurosteroid progesterone (PROG on stress-induced changes in urinary corticosterone (CORT levels, spatial memory and exploratory behavior.Castrated adult male rats were implanted with PROG or vehicle (VEHI,and then exposed for ten days to chronic stress created by overcrowding or ultrasonic noise. PROG and CORT levels were assessed in urine using highperformanceliquid chromatography (HPLC. Implanted PROG inhibited the rise of stress-induced CORT, prevented spatial memory impairment in the Morris water maze, and eliminated increased exploratory behavior in the hole-board test. These results suggest a protective role of PROG, possibly mediated by its anxiolytic mechanisms, against corticosteroids elevation and the behavioral deficit generated by stressful situations.

  3. Mori Folium and Mori Fructus Mixture Attenuates High-Fat Diet-Induced Cognitive Deficits in Mice

    Directory of Open Access Journals (Sweden)

    Hyo Geun Kim

    2015-01-01

    Full Text Available Obesity has become a global health problem, contributing to various diseases including diabetes, hypertension, cancer, and dementia. Increasing evidence suggests that obesity can also cause neuronal damage, long-term memory loss, and cognitive impairment. The leaves and the fruits of Morus alba L., containing active phytochemicals, have been shown to possess antiobesity and hypolipidemic properties. Thus, in the present study, we assessed their effects on cognitive functioning in mice fed a high-fat diet by performing immunohistochemistry, using antibodies against c-Fos, synaptophysin, and postsynaptic density protein 95 and a behavioral test. C57BL/6 mice fed a high-fat diet for 21 weeks exhibited increased body weight, but mice coadministered an optimized Mori Folium and Mori Fructus extract mixture (2 : 1; MFE for the final 12 weeks exhibited significant body weight loss. Additionally, obese mice exhibited not only reduced neural activity, but also decreased presynaptic and postsynaptic activities, while MFE-treated mice exhibited recovery of these activities. Finally, cognitive deficits induced by the high-fat diet were recovered by cotreatment with MFE in the novel object recognition test. Our findings suggest that the antiobesity effects of MFE resulted in recovery of the cognitive deficits induced by the high-fat diet by regulation of neural and synaptic activities.

  4. Chronic epigallocatechin-3-gallate ameliorates learning and memory deficits in diabetic rats via modulation of nitric oxide and oxidative stress.

    Science.gov (United States)

    Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad

    2011-10-31

    Due to anti-diabetic and antioxidant activity of green tea epigallocatechin gallate (EGCG) and the existence of evidence for its beneficial effect on cognition and memory, this research study was conducted to evaluate, for the first time, the efficacy of chronic EGCG on alleviation of learning and memory deficits in streptozotocin (STZ)-diabetic rats. Male Wistar rats were divided into control, diabetic, EGCG-treated-control and -diabetic groups. EGCG was administered at a dose of 20 and 40 mg/kg/day for 7 weeks. Learning and memory was evaluated using Y maze, passive avoidance, and radial 8-arm maze (RAM) tests. Oxidative stress markers and involvement of nitric oxide system were also evaluated. Alternation score of the diabetic rats in Y maze was lower than that of control and a significant impairment was observed in retention and recall in passive avoidance test (pRAM task and EGCG (40 mg/kg) significantly ameliorated these changes (pmemory respectively. Meanwhile, increased levels of malondialdehyde (MDA) and nitrite in diabetic rats significantly reduced due to EGCG treatment (pmemory deficits in STZ-diabetic rats through attenuation of oxidative stress and modulation of NO. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. The neural substrates of semantic memory deficits in early Alzheimer's disease: Clues from semantic priming effects and FDG-PET

    International Nuclear Information System (INIS)

    Giffard, B.; Laisney, M.; Mezenge, F.; De la Sayette, V.; Eustache, F.; Desgranges, B.

    2008-01-01

    The neural substrates responsible for semantic dysfunction during the early stages of AD have yet to be clearly identified. After a brief overview of the literature on normal and pathological semantic memory, we describe a new approach, designed to provide fresh insights into semantic deficits in AD. We mapped the correlations between resting-state brain glucose utilisation measured by FDG-PET and semantic priming scores in a group of 17 AD patients. The priming task, which yields a particularly pure measurement of semantic memory, was composed of related pairs of words sharing an attribute relationship (e.g. tiger-stripe). The priming scores correlated positively with the metabolism of the superior temporal areas on both sides, especially the right side, and this correlation was shown to be specific to the semantic priming effect.This pattern of results is discussed in the light of recent theoretical models of semantic memory, and suggests that a dysfunction of the right superior temporal cortex may contribute to early semantic deficits, characterised by the loss of specific features of concepts in AD. (authors)

  6. Study of ameliorating effects of ethanolic extract of Centella asiatica on learning and memory deficit in animal models.

    Science.gov (United States)

    Doknark, Saowalak; Mingmalairak, Salin; Vattanajun, Anusara; Tantisira, Boonyong; Tantisira, Mayuree H

    2014-02-01

    The present study investigated the effect of Centella asiatica ethanolic extract (CE) on learning and memoly imnpairment induced by either transient bilateral common carotid arteries occlusion (T2 VO) or an intraperitoneal injection of scopolamine in mice. CE (100, 300, 1000 or 1500 mg/kg, p.o.) were administered to learning and memory impaired mice once daily for 8 consecutive days. Learning and memory performance were evaluated by Morris water maze (MWM) and step-down passive avoidance (PA) test. Changes in malondialdehyde (MDA) levels in the brain were determined by lipid peroxidation assay. T2 VO mice exhibited learning and memory impairment in the MWM and PA tests. Treatment with CE ameliorated the learning and memory impairment of T2VO mice. Furthermore, CE significantly reduced MDA level in the brain of T2VO mice. On the other hand, administration of CE did not attenuate learning and memory impairment induced by scopolamine in mice. The present study demonstrated ameliorating effect of CE on learning and memory impairment in T2VO mice. Furthermore, it is likely that the positive effect of CE observed could be, at least partly, accounted by its antioxidative property. Thus, CE might be beneficial for memory impairment in which oxidative stress is an underlying cause.

  7. The antineoplastic drug flavopiridol reverses memory impairment induced by Amyloid-ß1-42 oligomers in mice.

    Science.gov (United States)

    Leggio, Gian Marco; Catania, Maria Vincenza; Puzzo, Daniela; Spatuzza, Michela; Pellitteri, Rosalia; Gulisano, Walter; Torrisi, Sebastiano Alfio; Giurdanella, Giovanni; Piazza, Cateno; Impellizzeri, Agata Rita; Gozzo, Lucia; Navarria, Andrea; Bucolo, Claudio; Nicoletti, Ferdinando; Palmeri, Agostino; Salomone, Salvatore; Copani, Agata; Caraci, Filippo; Drago, Filippo

    2016-04-01

    The ectopic re-activation of cell cycle in neurons is an early event in the pathogenesis of Alzheimer's disease (AD), which could lead to synaptic failure and ensuing cognitive deficits before frank neuronal death. Cytostatic drugs that act as cyclin-dependent kinase (CDK) inhibitors have been poorly investigated in animal models of AD. In the present study, we examined the effects of flavopiridol, an inhibitor of CDKs currently used as antineoplastic drug, against cell cycle reactivation and memory loss induced by intracerebroventricular injection of Aß1-42 oligomers in CD1 mice. Cycling neurons, scored as NeuN-positive cells expressing cyclin A, were found both in the frontal cortex and in the hippocampus of Aβ-injected mice, paralleling memory deficits. Starting from three days after Aβ injection, flavopiridol (0.5, 1 and 3mg/kg) was intraperitoneally injected daily, for eleven days. Here we show that a treatment with flavopiridol (0.5 and 1mg/kg) was able to rescue the loss of memory induced by Aβ1-42, and to prevent the occurrence of ectopic cell-cycle events in the mouse frontal cortex and hippocampus. This is the first evidence that a cytostatic drug can prevent cognitive deficits in a non-transgenic animal model of AD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia.

    Science.gov (United States)

    Galeano, Pablo; Blanco, Eduardo; Logica Tornatore, Tamara M A; Romero, Juan I; Holubiec, Mariana I; Rodríguez de Fonseca, Fernando; Capani, Francisco

    2014-01-01

    Continuous environmental stimulation induced by exposure to enriched environment (EE) has yielded cognitive benefits in different models of brain injury. Perinatal asphyxia results from a lack of oxygen supply to the fetus and is associated with long-lasting neurological deficits. However, the effects of EE in middle-aged rats suffering perinatal asphyxia are unknown. Therefore, the aim of the present study was to assess whether life-long exposure to EE could counteract the cognitive and behavioral alterations in middle-aged asphyctic rats. Experimental groups consisted of rats born vaginally (CTL), by cesarean section (C+), or by C+ following 19 min of asphyxia at birth (PA). At weaning, rats were assigned to standard (SE) or enriched environment (EE) for 18 months. During the last month of housing, animals were submitted to a behavioral test battery including Elevated Plus Maze, Open Field, Novel Object Recognition and Morris water maze (MWM). Results showed that middle-aged asphyctic rats, reared in SE, exhibited an impaired performance in the spatial reference and working memory versions of the MWM. EE was able to counteract these cognitive impairments. Moreover, EE improved the spatial learning performance of middle-aged CTL and C+ rats. On the other hand, all groups reared in SE did not differ in locomotor activity and anxiety levels, while EE reduced locomotion and anxiety, regardless of birth condition. Recognition memory was altered neither by birth condition nor by housing environment. These results support the importance of environmental stimulation across the lifespan to prevent cognitive deficits induced by perinatal asphyxia.

  9. Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia

    Science.gov (United States)

    Galeano, Pablo; Blanco, Eduardo; Logica Tornatore, Tamara M. A.; Romero, Juan I.; Holubiec, Mariana I.; Rodríguez de Fonseca, Fernando; Capani, Francisco

    2015-01-01

    Continuous environmental stimulation induced by exposure to enriched environment (EE) has yielded cognitive benefits in different models of brain injury. Perinatal asphyxia results from a lack of oxygen supply to the fetus and is associated with long-lasting neurological deficits. However, the effects of EE in middle-aged rats suffering perinatal asphyxia are unknown. Therefore, the aim of the present study was to assess whether life-long exposure to EE could counteract the cognitive and behavioral alterations in middle-aged asphyctic rats. Experimental groups consisted of rats born vaginally (CTL), by cesarean section (C+), or by C+ following 19 min of asphyxia at birth (PA). At weaning, rats were assigned to standard (SE) or enriched environment (EE) for 18 months. During the last month of housing, animals were submitted to a behavioral test battery including Elevated Plus Maze, Open Field, Novel Object Recognition and Morris water maze (MWM). Results showed that middle-aged asphyctic rats, reared in SE, exhibited an impaired performance in the spatial reference and working memory versions of the MWM. EE was able to counteract these cognitive impairments. Moreover, EE improved the spatial learning performance of middle-aged CTL and C+ rats. On the other hand, all groups reared in SE did not differ in locomotor activity and anxiety levels, while EE reduced locomotion and anxiety, regardless of birth condition. Recognition memory was altered neither by birth condition nor by housing environment. These results support the importance of environmental stimulation across the lifespan to prevent cognitive deficits induced by perinatal asphyxia. PMID:25601829

  10. Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia

    Directory of Open Access Journals (Sweden)

    Pablo eGaleano

    2015-01-01

    Full Text Available Continuous environmental stimulation induced by exposure to enriched environment (EE has yielded cognitive benefits in different models of brain injury. Perinatal asphyxia results from a lack of oxygen supply to the fetus and is associated with long-lasting neurological deficits. However, the effects of EE in middle-aged rats suffering perinatal asphyxia are unknown. Therefore, the aim of the present study was to assess whether life-long exposure to EE could counteract the cognitive and behavioral alterations in middle-aged asphyctic rats. Experimental groups consisted of rats born vaginally (CTL, by cesarean section (C+, or by C+ following 19 min of asphyxia at birth (PA. At weaning, rats were assigned to standard (SE or enriched environment (EE for 18 months. During the last month of housing, animals were submitted to a behavioral test battery including Elevated Plus Maze, Open Field, Novel Object Recognition and Morris water maze (MWM. Results showed that middle-aged asphyctic rats, reared in SE, exhibited an impaired performance in the spatial reference and working memory versions of the MWM. EE was able to counteract these cognitive impairments. Moreover, EE improved the spatial learning performance of middle-aged CTL and C+ rats. On the other hand, all groups reared in SE did not differ in locomotor activity and anxiety levels, while EE reduced locomotion and anxiety, regardless of birth condition. Recognition memory was altered neither by birth condition nor by housing environment. These results support the importance of environmental stimulation across the lifespan to prevent cognitive deficits induced by perinatal asphyxia.

  11. Nitrogen induced modifications of MANOS memory properties

    Energy Technology Data Exchange (ETDEWEB)

    Nikolaou, N., E-mail: n.nikolaou@inn.demokritos.gr [Institute of Nanoscience and Nanotechnology, NCSR “Demokritos”, 153 10 Athens (Greece); Department of Physics, University of Patras, 265 04 Patras (Greece); Ioannou-Sougleridis, V.; Dimitrakis, P.; Normand, P. [Institute of Nanoscience and Nanotechnology, NCSR “Demokritos”, 153 10 Athens (Greece); Skarlatos, D. [Department of Physics, University of Patras, 265 04 Patras (Greece); Giannakopoulos, K. [Institute of Nanoscience and Nanotechnology, NCSR “Demokritos”, 153 10 Athens (Greece); Ladas, S. [Department of Chemical Engineering, University of Patras, 265 04 Patras (Greece); Pecassou, B.; BenAssayag, G. [CEMES-CNRS, Toulouse (France); Kukli, K. [Department of Chemistry, University of Helsinki, FI-00014 Helsinki (Finland); Institute of Physics, University of Tartu, Ravila 14c, EE-50411 Tartu (Estonia); Niinistö, J.; Ritala, M.; Leskelä, M. [Department of Chemistry, University of Helsinki, FI-00014 Helsinki (Finland)

    2015-12-15

    In this work we examine the structural and electrical properties including the memory performance of Al{sub 2}O{sub 3}/Si{sub 3}N{sub 4}/SiO{sub 2} dielectric stacks implanted with low-energy nitrogen ions and subsequently thermal annealed at 850 or 1050 °C for 15 min. X-ray photoelectron spectroscopy reveals that the concentration and the chemical state of the nitrogen atoms within the Al{sub 2}O{sub 3} layer depends on the post-implantation annealing (PIA) temperature. Memory testing, performed on platinum gate capacitors, shows that charge retention of the programmed states is significantly improved for the high-temperature PIA samples as compared to the non-implanted samples. While such an improvement is not detected for the low-temperature PIA samples, the latter exhibit enhanced hole charging and thus, increased erase efficiency. Overall, our results suggest that the transport properties which control the erase and the retention characteristics of the blocking Al{sub 2}O{sub 3} layer can be tailored by nitrogen implantation and the PIA conditions and can be used for memory performance optimization.

  12. Reference and working memory deficits in the 3xTg-AD mouse between 2 and 15-months of age: a cross-sectional study.

    Science.gov (United States)

    Stevens, Leanne M; Brown, Richard E

    2015-02-01

    Impairments in working memory (WM) can predict the shift from mild cognitive impairment (MCI) to Alzheimer's disease (AD) and the rate at which AD progresses with age. The 3xTg-AD mouse model develops both Aβ plaques and neurofibrillary tangles, the neuro-pathological hallmarks of AD, by 6 months of age, but no research has investigated the age-related changes in WM in these mice. Using a cross-sectional design, we tested male and female 3xTg-AD and wildtype control (B6129SF2/J) mice between 2 and 15 months of age for reference and working memory errors in the 8-arm radial maze. The 3xTg-AD mice had deficits in both working and reference memory across the ages tested, rather than showing the predicted age-related memory deficits. Male 3xTg-AD mice showed more working and reference memory errors than females, but there were no sex differences in wildtype control mice. These results indicate that the 3xTg-AD mouse replicates the impairments in WM found in patients with AD. However, these mice show memory deficits as early as two months of age, suggesting that the genes underlying reference and working memory in these mice cause deficits from an early age. The finding that males were affected more than females suggests that more attention should be paid to sex differences in transgenic AD mice. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Retrieval-Induced Inhibition in Short-Term Memory.

    Science.gov (United States)

    Kang, Min-Suk; Choi, Joongrul

    2015-07-01

    We used a visual illusion called motion repulsion as a model system for investigating competition between two mental representations. Subjects were asked to remember two random-dot-motion displays presented in sequence and then to report the motion directions for each. Remembered motion directions were shifted away from the actual motion directions, an effect similar to the motion repulsion observed during perception. More important, the item retrieved second showed greater repulsion than the item retrieved first. This suggests that earlier retrieval exerted greater inhibition on the other item being held in short-term memory. This retrieval-induced motion repulsion could be explained neither by reduced cognitive resources for maintaining short-term memory nor by continued inhibition between short-term memory representations. These results indicate that retrieval of memory representations inhibits other representations in short-term memory. We discuss mechanisms of retrieval-induced inhibition and their implications for the structure of memory. © The Author(s) 2015.

  14. Detection of prospective memory deficits in mild cognitive impairment of suspected Alzheimer's disease etiology using a novel event-based prospective memory task.

    LENUS (Irish Health Repository)

    Blanco-Campal, Alberto

    2009-01-01

    We investigated the relative discriminatory efficacy of an event-based prospective memory (PM) task, in which specificity of the instructions and perceptual salience of the PM cue were manipulated, compared with two widely used retrospective memory (RM) tests (Rivermead Paragraph Recall Test and CERAD-Word List Test), when detecting mild cognitive impairment of suspected Alzheimer\\'s disease etiology (MCI-AD) (N = 19) from normal controls (NC) (N = 21). Statistical analyses showed high discriminatory capacity of the PM task for detecting MCI-AD. The Non-Specific-Non-Salient condition proved particularly useful in detecting MCI-AD, possibly reflecting the difficulty of the task, requiring more strategic attentional resources to monitor for the PM cue. With a cutoff score of <4\\/10, the Non-Specific-Non-Salient condition achieved a sensitivity = 84%, and a specificity = 95%, superior to the most discriminative RM test used (CERAD-Total Learning: sensitivity = 83%; specificity = 76%). Results suggest that PM is an early sign of memory failure in MCI-AD and may be a more pronounced deficit than retrospective failure, probably reflecting the greater self-initiated retrieval demands involved in the PM task used. Limitations include the relatively small sample size, and the use of a convenience sample (i.e. memory clinic attenders and healthy active volunteers), reducing the generalizability of the results, which should be regarded as preliminary. (JINS, 2009, 15, 154-159.).

  15. Antiamnesic Effects of a Hydroethanolic Extract of Crinum macowanii on Scopolamine-Induced Memory Impairment in Mice.

    Science.gov (United States)

    Mugwagwa, Andrew T; Gadaga, Louis L; Pote, William; Tagwireyi, Dexter

    2015-01-01

    Crinum macowanii has been found to contain alkaloids that have activity against acetylcholinesterase enzyme in vitro. The present study was undertaken to investigate the in vivo ability of hydroethanolic crude extract of Crinum macowanii to ameliorate memory impairment induced by scopolamine. Thirty-six male Balb/c mice weighing around 25-35 g were employed in the present investigation. Y-maze and novel object recognition apparatus served as the exteroceptive behavioural models, and scopolamine-induced amnesia served as the interoceptive behavioural model. C. macowanii (10, 20, and 40 mg/kg p.o.) was administered in single doses to the mice. Donepezil (3 mg/kg p.o.) was used as a positive control agent. C. macowanii extract reversed the amnesia induced by scopolamine as indicated by a dose-dependent increase in spontaneous alternation performance in the Y-maze task. C. macowanii 40 mg/kg showed significant activity (p memory-enhancing activity against scopolamine-induced memory deficits in the long-term memory novel object recognition performance as indicated by a dose-dependent increase in the discrimination index. The results indicate that the hydroethanolic extract of C. macowanii may be a useful memory restorative mediator in the treatment of cognitive disorders such as Alzheimer's disease.

  16. Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

    Science.gov (United States)

    Oliver, Jason A; Evans, David E; Addicott, Merideth A; Potts, Geoffrey F; Brandon, Thomas H; Drobes, David J

    2017-06-01

    Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p nicotine dependence (p Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and

  17. Spatial-memory deficit in schizophrenia spectrum disorders under viewpoint-independent demands in the virtual courtyard task.

    Science.gov (United States)

    Wilkins, Leanne K; Girard, Todd A; King, Jelena; King, Matthew J; Herdman, Katherine A; Christensen, Bruce K; King, John

    2013-01-01

    This study builds upon our previous work indicating that impaired hippocampal-dependent forms of memory are core to schizophrenia. Using a virtual-reality courtyard task, we presented participants with schizophrenia spectrum disorders (SSD; n = 20) and a healthy community comparison group (n = 20) with objects to remember within a town square, followed by a recognition test of the location of objects from either the same viewpoint or a shifted viewpoint relative to initial presentation. The SSD group demonstrated a relative deficit under shifted- compared to same-view conditions. These findings provide further support for deficient hippocampal-dependent cognition in SSD.

  18. EEG markers of reduced visual short-term memory capacity in adult attention deficit/hyperactivity disorder

    DEFF Research Database (Denmark)

    Wiegand, Iris Michaela; Kilian, Beate; Hennig-Fast, Kristina

    2015-01-01

    Attention deficit hyperactivity disorder (ADHD) persists frequently into adulthood. The disease is associated with difficulties in many cognitive tasks, which are assumed to be caused by neurobiologically-based basal dysfunctions. A reduction in visual working memory storage capacity has recently...... in individuals with higher compared to lower storage capacity. A later section of the CP was further overall increased in the group of ADHD patients relative to controls. Together, the findings indicate that ADHD patients show disease-specific changes in brain mechanisms underlying visual storage capacity...

  19. Ursolic acid improves domoic acid-induced cognitive deficits in mice

    International Nuclear Information System (INIS)

    Wu, Dong-mei; Lu, Jun; Zhang, Yan-qiu; Zheng, Yuan-lin; Hu, Bin; Cheng, Wei; Zhang, Zi-feng; Li, Meng-qiu

    2013-01-01

    Our previous findings suggest that mitochondrial dysfunction is the mechanism underlying cognitive deficits induced by domoic acid (DA). Ursolic acid (UA), a natural triterpenoid compound, possesses many important biological functions. Evidence shows that UA can activate PI3K/Akt signaling and suppress Forkhead box protein O1 (FoxO1) activity. FoxO1 is an important regulator of mitochondrial function. Here we investigate whether FoxO1 is involved in the oxidative stress-induced mitochondrial dysfunction in DA-treated mice and whether UA inhibits DA-induced mitochondrial dysfunction and cognitive deficits through regulating the PI3K/Akt and FoxO1 signaling pathways. Our results showed that FoxO1 knockdown reversed the mitochondrial abnormalities and cognitive deficits induced by DA in mice through decreasing HO-1 expression. Mechanistically, FoxO1 activation was associated with oxidative stress-induced JNK activation and decrease of Akt phosphorylation. Moreover, UA attenuated the mitochondrial dysfunction and cognitive deficits through promoting Akt phosphorylation and FoxO1 nuclear exclusion in the hippocampus of DA-treated mice. LY294002, an inhibitor of PI3K/Akt signaling, significantly decreased Akt phosphorylation in the hippocampus of DA/UA mice, which weakened UA actions. These results suggest that UA could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in excitotoxic brain disorders. - Highlights: • Ursolic acid (UA) is a naturally triterpenoid compound. • UA attenuated the mitochondrial dysfunction and cognitive deficits. • Mechanistically, UA activates PI3K/Akt signaling and suppresses FoxO1 activity. • UA could be recommended as a possible candidate for anti-excitotoxic brain disorders

  20. Ursolic acid improves domoic acid-induced cognitive deficits in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Dong-mei [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Lu, Jun, E-mail: lu-jun75@163.com [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Zhang, Yan-qiu [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Zheng, Yuan-lin, E-mail: ylzheng@xznu.edu.cn [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Hu, Bin [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Cheng, Wei [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Zhang, Zi-feng; Li, Meng-qiu [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China)

    2013-09-01

    Our previous findings suggest that mitochondrial dysfunction is the mechanism underlying cognitive deficits induced by domoic acid (DA). Ursolic acid (UA), a natural triterpenoid compound, possesses many important biological functions. Evidence shows that UA can activate PI3K/Akt signaling and suppress Forkhead box protein O1 (FoxO1) activity. FoxO1 is an important regulator of mitochondrial function. Here we investigate whether FoxO1 is involved in the oxidative stress-induced mitochondrial dysfunction in DA-treated mice and whether UA inhibits DA-induced mitochondrial dysfunction and cognitive deficits through regulating the PI3K/Akt and FoxO1 signaling pathways. Our results showed that FoxO1 knockdown reversed the mitochondrial abnormalities and cognitive deficits induced by DA in mice through decreasing HO-1 expression. Mechanistically, FoxO1 activation was associated with oxidative stress-induced JNK activation and decrease of Akt phosphorylation. Moreover, UA attenuated the mitochondrial dysfunction and cognitive deficits through promoting Akt phosphorylation and FoxO1 nuclear exclusion in the hippocampus of DA-treated mice. LY294002, an inhibitor of PI3K/Akt signaling, significantly decreased Akt phosphorylation in the hippocampus of DA/UA mice, which weakened UA actions. These results suggest that UA could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in excitotoxic brain disorders. - Highlights: • Ursolic acid (UA) is a naturally triterpenoid compound. • UA attenuated the mitochondrial dysfunction and cognitive deficits. • Mechanistically, UA activates PI3K/Akt signaling and suppresses FoxO1 activity. • UA could be recommended as a possible candidate for anti-excitotoxic brain disorders.

  1. Phytoceramide Shows Neuroprotection and Ameliorates Scopolamine-Induced Memory Impairment

    Directory of Open Access Journals (Sweden)

    Seikwan Oh

    2011-10-01

    Full Text Available The function and the role phytoceramide (PCER and phytosphingosine (PSO in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o. recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer’s disease.

  2. Phytoceramide shows neuroprotection and ameliorates scopolamine-induced memory impairment.

    Science.gov (United States)

    Jung, Jae-Chul; Lee, Yeonju; Moon, Sohyeon; Ryu, Jong Hoon; Oh, Seikwan

    2011-10-28

    The function and the role phytoceramide (PCER) and phytosphingosine (PSO) in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS) showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o.) recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it