Gastrodia elata Bl. Attenuated learning deficits induced by forced-swimming stress in the inhibitory avoidance task and Morris water maze.

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Chen, Pei-Ju; Liang, Keng-Chen; Lin, Hui-Chen; Hsieh, Ching-Liang; Su, Kuan-Pin; Hung, Mei-Chu; Sheen, Lee-Yan

2011-06-01

This study adopted the forced-swimming paradigm to induce depressive symptoms in rats and evaluated the effects on learning and memory processing. Furthermore, the effects of the water extract of Gastrodia elata Bl., a well-known Chinese traditional medicine, on amnesia in rats subjected to the forced-swimming procedure were studied. Rats were subjected to the forced-swimming procedure, and the inhibitory avoidance task and Morris water maze were used to assess learning and memory performance. The acquisition of the two tasks was mostly impaired after the 15-minute forced-swimming procedure. Administration of the water extract of G. elata Bl. for 21 consecutive days at a dosage of 0.5 or 1.0 g/kg of body weight significantly improved retention in the inhibitory avoidance test, and the lower dose showed a better effect than the higher one and the antidepressant fluoxetine (18 mg/kg of body weight). In the Morris water maze, the lower dose of the water extract of G. elata Bl. significantly improved retention by shortening escape latency in the first test session and increasing the time in searching the target zone during the probe test. These findings suggest that water extracts of G. elata Bl. ameliorate the learning and memory deficits induced by forced swimming.

Prenatal treatment prevents learning deficit in Down syndrome model.

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Incerti, Maddalena; Horowitz, Kari; Roberson, Robin; Abebe, Daniel; Toso, Laura; Caballero, Madeline; Spong, Catherine Y

2012-01-01

Down syndrome is the most common genetic cause of mental retardation. Active fragments of neurotrophic factors release by astrocyte under the stimulation of vasoactive intestinal peptide, NAPVSIPQ (NAP) and SALLRSIPA (SAL) respectively, have shown therapeutic potential for developmental delay and learning deficits. Previous work demonstrated that NAP+SAL prevent developmental delay and glial deficit in Ts65Dn that is a well-characterized mouse model for Down syndrome. The objective of this study is to evaluate if prenatal treatment with these peptides prevents the learning deficit in the Ts65Dn mice. Pregnant Ts65Dn female and control pregnant females were randomly treated (intraperitoneal injection) on pregnancy days 8 through 12 with saline (placebo) or peptides (NAP 20 µg +SAL 20 µg) daily. Learning was assessed in the offspring (8-10 months) using the Morris Watermaze, which measures the latency to find the hidden platform (decrease in latency denotes learning). The investigators were blinded to the prenatal treatment and genotype. Pups were genotyped as trisomic (Down syndrome) or euploid (control) after completion of all tests. two-way ANOVA followed by Neuman-Keuls test for multiple comparisons, PDown syndrome-placebo; n = 11) did not demonstrate learning over the five day period. DS mice that were prenatally exposed to peptides (Down syndrome-peptides; n = 10) learned significantly better than Down syndrome-placebo (ptreatment with the neuroprotective peptides (NAP+SAL) prevented learning deficits in a Down syndrome model. These findings highlight a possibility for the prevention of sequelae in Down syndrome and suggest a potential pregnancy intervention that may improve outcome.

Enriched environment ameliorates depression-induced cognitive deficits and restores abnormal hippocampal synaptic plasticity.

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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.

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

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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.

Deficits of learning and memory in Hemojuvelin knockout mice.

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Li, Jinglong; Zhang, Peng; Liu, Hongju; Ren, Wei; Song, Jinjing; Rao, Elizabeth; Takahashi, Eiki; Zhou, Ying; Li, Weidong; Chen, Xiaoping

2015-10-01

Iron is involved in various physiological processes of the human body to maintain normal functions. Abnormal iron accumulation in brain has been reported as a pathogenesis of several neurodegenerative disorders and cognitive impairments. Hemojuvelin (HVJ) is a membrane-bound and soluble protein in mammals that is responsible for the iron overload condition known as juvenile hemochromatosis. Although iron accumulation in brain has been related to neurodegenerative diseases, it remains unknown the effect of mutation of HVJ gene on cognitive performance. In our studies, HJV(-/-) mice showed deficits in novel object recognition and Morris water maze tests. Furthermore, the expression ration of apoptotic marker Bax and anti-apoptotic marker Bcl-2 in the hippocampus and prefrontal cortex showed higher levels in HJV(-/-) mice. Our results suggested that deletion of HJV gene could increase apoptosis in brain which might contribute to learning and memory deficits in mutant mice. These results indicated that HJV(-/-) mice would be a useful model to study cognitive impairment induced by iron overload in brain.

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

Uncaria rhynchophylla ameliorates cognitive deficits induced by D-galactose in mice.

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Xian, Yan-Fang; Lin, Zhi-Xiu; Zhao, Ming; Mao, Qing-Qiu; Ip, Siu-Po; Che, Chun-Tao

2011-12-01

The stem with hooks of Uncaria rhynchophylla is a component herb of many traditional formulae for the treatment of neurodegenerative diseases. However, scientific evidence of the efficacy of Uncaria rhynchophylla in the treatment of Alzheimer's disease (AD) in animal models is lacking. Thus, in the present study, we investigated whether the 70 % aqueous ethanol extract of Uncaria rhynchophylla (EUR) could protect against D-galactose (D-gal)-induced cognitive deficits in mice. Mice were given a subcutaneous injection of D-gal (50 mg/kg) and orally administered EUR (100, 200, or 400 mg/kg) daily for 8 weeks. The effect of EUR on D-gal-induced cognitive deficits was evaluated by measuring behavioral and neurochemical parameters of AD and the antioxidant status of brain tissue. The results showed that EUR (200 or 400 mg/kg) significantly increased exploratory behavior (assessed by an open-field test) and improved spatial learning and memory function (assessed by the Morris water maze test) in D-gal-treated mice. In addition, EUR (200 or 400 mg/kg) significantly increased the levels of acetylcholine and glutathione and decreased the activity of acetylcholinesterase and the level of malondialdehyde in the brains of D-gal-treated mice. These results indicate that EUR ameliorates cognitive deficits induced by D-gal in mice, and that this action may be mediated, at least in part, by the inhibition of acetylcholinesterase activity and the enhancement of the antioxidant status of brain tissue. © Georg Thieme Verlag KG Stuttgart · New York.

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.

Different MK-801 administration schedules induce mild to severe learning impairments in an operant conditioning task: role of buspirone and risperidone in ameliorating these cognitive deficits.

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Rapanelli, Maximiliano; Frick, Luciana Romina; Bernardez-Vidal, Micaela; Zanutto, Bonifacio Silvano

2013-11-15

Blockade of N-methyl-d-aspartate receptor (NMDA) by the noncompetitive NMDA receptor (NMDAR) antagonist MK-801 produces behavioral abnormalities and alterations in prefrontal cortex (PFC) functioning. Due to the critical role of the PFC in operant conditioning task learning, we evaluated the effects of acute, repeated postnatal injections of MK-801 (0.1mg/kg) on learning performance. We injected Long-Evans rats i.p. with MK-801 (0.1mg/kg) using three different administration schedules: injection 40 min before beginning the task (during) (n=12); injection twice daily for six consecutive days prior to beginning the experimental procedures (prior) (n=12); or twice daily subcutaneous injections from postnatal day 7 to 11 (postnatal) (n=12). Next, we orally administered risperidone (serotonin receptor 2A and dopamine receptor 2 antagonist, 1mg/kg) or buspirone (serotonin receptor 1A partial agonist, 10mg/kg) to animals treated with the MK-801 schedule described above. The postnatal and prior administration schedules produced severe learning deficits, whereas injection of MK-801 just before training sessions had only mild effects on acquisition of an operant conditioning. Risperidone was able to reverse the detrimental effect of MK-801 in the animals that were treated with MK-801 during and prior training sessions. In contrast, buspirone was only effective at mitigating the cognitive deficits induced by MK-801 when administered during the training procedures. The data demonstrates that NMDA antagonism disrupts basic mechanisms of learning in a simple PFC-mediated operant conditioning task, and that buspirone and risperidone failed to attenuate the learning deficits when NMDA neurotransmission was blocked in the early stages of the postnatal period. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Organizational Learning Strategies and Verbal Memory Deficits in Bipolar Disorder.

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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).

Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats.

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Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

2015-04-01

Previous results indicated that stress impairs learning and memory. In this research, the effects of preventive, therapeutic and regular continually running activity on chronic stress-induced memory deficit in rats were investigated. 70 male rats were randomly divided into seven groups as follows: Control, Sham, Stress-Rest, Rest-Stress, Stress-Exercise, Exercise-Stress and Exercise-Stress & Exercise groups. Chronic restraint stress was applied 6 h/day for 21days and treadmill running 1 h/day. Memory function was evaluated by the passive avoidance test. The results revealed that running activities had therapeutic effect on mid and long-term memory deficit and preventive effects on short and mid-term memory deficit in stressed rats. Regular continually running activity improved mid and long-term memory compared to Exercise-Stress group. The beneficial effects of exercise were time-dependent in stress conditions. Finally, data corresponded to the possibility that treadmill running had a more important role on treatment rather than on prevention on memory impairment induced by stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

Linking aβ42-induced hyperexcitability to neurodegeneration, learning and motor deficits, and a shorter lifespan in an Alzheimer's model.

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Yong Ping

2015-03-01

Full Text Available Alzheimer's disease (AD is the most prevalent form of dementia in the elderly. β-amyloid (Aβ accumulation in the brain is thought to be a primary event leading to eventual cognitive and motor dysfunction in AD. Aβ has been shown to promote neuronal hyperactivity, which is consistent with enhanced seizure activity in mouse models and AD patients. Little, however, is known about whether, and how, increased excitability contributes to downstream pathologies of AD. Here, we show that overexpression of human Aβ42 in a Drosophila model indeed induces increased neuronal activity. We found that the underlying mechanism involves the selective degradation of the A-type K+ channel, Kv4. An age-dependent loss of Kv4 leads to an increased probability of AP firing. Interestingly, we find that loss of Kv4 alone results in learning and locomotion defects, as well as a shortened lifespan. To test whether the Aβ42-induced increase in neuronal excitability contributes to, or exacerbates, downstream pathologies, we transgenically over-expressed Kv4 to near wild-type levels in Aβ42-expressing animals. We show that restoration of Kv4 attenuated age-dependent learning and locomotor deficits, slowed the onset of neurodegeneration, and partially rescued premature death seen in Aβ42-expressing animals. We conclude that Aβ42-induced hyperactivity plays a critical role in the age-dependent cognitive and motor decline of this Aβ42-Drosophila model, and possibly in AD.

Caffeine improves spatial learning deficits in an animal model of attention deficit hyperactivity disorder (ADHD) -- the spontaneously hypertensive rat (SHR).

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Prediger, Rui D S; Pamplona, Fabrício A; Fernandes, Daniel; Takahashi, Reinaldo N

2005-12-01

The spontaneously hypertensive rat (SHR) is generally considered to be a suitable genetic model for the study of attention deficit hyperactivity disorder (ADHD), since it displays hyperactivity, impulsivity, poorly sustained attention, and deficits in learning and memory processes. Converging evidence suggests a primary role of disturbance in the dopaminergic neurotransmission in ADHD patients and in SHR, and in addition, some studies have also demonstrated alterations in adenosinergic neurotransmission in SHR. In the present study, adult female Wistar (WIS) and SHR rats received caffeine (1-10 mg/kg i.p.) 30 min before training, immediately after training, or 30 min before a test session in the spatial version of the Morris water maze. The effect of caffeine administration on WIS and SHR blood pressure was also measured. SHR needed significantly more trials in the training session to acquire the spatial information, but they displayed a similar profile to that of WIS rats in the test session (48 h later), demonstrating a selective deficit in spatial learning. Pre-training administration of caffeine (1-10 mg/kg i.p.) improved this spatial learning deficit in SHR, but did not alter the WIS performance. In contrast, post-training administration of caffeine (3 mg/kg i.p.) did not alter the SHR test performance, but increased memory retention in WIS rats. No dose of caffeine tested altered the mean blood pressure of WIS or SHR. These results demonstrate a selective spatial learning deficit in SHR which can be attenuated by pre-training administration of caffeine. In addition, the present findings indicate that the spatial learning deficit in SHR is not directly related to hypertension.

Ursolic acid improves domoic acid-induced cognitive deficits in mice

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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

Ursolic acid improves domoic acid-induced cognitive deficits in mice

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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.

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.

The synthetic cannabinoid HU210 induces spatial memory deficits and suppresses hippocampal firing rate in rats.

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Robinson, L; Goonawardena, A V; Pertwee, R G; Hampson, R E; Riedel, G

2007-07-01

Previous work implied that the hippocampal cannabinoid system was particularly important in some forms of learning, but direct evidence for this hypothesis is scarce. We therefore assessed the effects of the synthetic cannabinoid HU210 on memory and hippocampal activity. HU210 (100 microg kg(-1)) was administered intraperitoneally to rats under three experimental conditions. One group of animals were pre-trained in spatial working memory using a delayed-matching-to-position task and effects of HU210 were assessed in a within-subject design. In another, rats were injected before acquisition learning of a spatial reference memory task with constant platform location. Finally, a separate group of animals was implanted with electrode bundles in CA1 and CA3 and single unit responses were isolated, before and after HU210 treatment. HU210 treatment had no effect on working or short-term memory. Relative to its control Tween 80, deficits in acquisition of a reference memory version of the water maze were obtained, along with drug-related effects on anxiety, motor activity and spatial learning. Deficits were not reversed by the CB(1) receptor antagonists SR141716A (3 mg kg(-1)) or AM281 (1.5 mg kg(-1)). Single unit recordings from principal neurons in hippocampal CA3 and CA1 confirmed HU210-induced attenuation of the overall firing activity lowering both the number of complex spikes fired and the occurrence of bursts. These data provide the first direct evidence that the underlying mechanism for the spatial memory deficits induced by HU210 in rats is the accompanying abnormality in hippocampal cell firing.

Memory Deficits Induced by Inflammation Are Regulated by α5-Subunit-Containing GABAA Receptors

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Dian-Shi Wang

2012-09-01

Full Text Available Systemic inflammation causes learning and memory deficits through mechanisms that remain poorly understood. Here, we studied the pathogenesis of memory loss associated with inflammation and found that we could reverse memory deficits by pharmacologically inhibiting α5-subunit-containing γ-aminobutyric acid type A (α5GABAA receptors and deleting the gene associated with the α5 subunit. Acute inflammation reduces long-term potentiation, a synaptic correlate of memory, in hippocampal slices from wild-type mice, and this reduction was reversed by inhibition of α5GABAA receptor function. A tonic inhibitory current generated by α5GABAA receptors in hippocampal neurons was increased by the key proinflammatory cytokine interleukin-1β through a p38 mitogen-activated protein kinase signaling pathway. Interleukin-1β also increased the surface expression of α5GABAA receptors in the hippocampus. Collectively, these results show that α5GABAA receptor activity increases during inflammation and that this increase is critical for inflammation-induced memory deficits.

Specific Deficit in Implicit Motor Sequence Learning following Spinal Cord Injury.

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Ayala Bloch

Full Text Available Physical and psychosocial rehabilitation following spinal cord injury (SCI leans heavily on learning and practicing new skills. However, despite research relating motor sequence learning to spinal cord activity and clinical observations of impeded skill-learning after SCI, implicit procedural learning following spinal cord damage has not been examined.To test the hypothesis that spinal cord injury (SCI in the absence of concomitant brain injury is associated with a specific implicit motor sequence learning deficit that cannot be explained by depression or impairments in other cognitive measures.Ten participants with SCI in T1-T11, unharmed upper limb motor and sensory functioning, and no concomitant brain injury were compared to ten matched control participants on measures derived from the serial reaction time (SRT task, which was used to assess implicit motor sequence learning. Explicit generation of the SRT sequence, depression, and additional measures of learning, memory, and intelligence were included to explore the source and specificity of potential learning deficits.There was no between-group difference in baseline reaction time, indicating that potential differences between the learning curves of the two groups could not be attributed to an overall reduction in response speed in the SCI group. Unlike controls, the SCI group showed no decline in reaction time over the first six blocks of the SRT task and no advantage for the initially presented sequence over the novel interference sequence. Meanwhile, no group differences were found in explicit learning, depression, or any additional cognitive measures.The dissociation between impaired implicit learning and intact declarative memory represents novel empirical evidence of a specific implicit procedural learning deficit following SCI, with broad implications for rehabilitation and adjustment.

Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits

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Liu, Xiao; Li, Jitao; Guo, Chunmei; Wang, Hongli; Sun, Yaxin; Wang, Han; Su, Yun-Ai; Li, Keqing; Si, Tianmei

2018-01-01

Cognitive dysfunction constitutes an essential component in schizophrenia for its early presence in the pathophysiology of the disease and close relatedness to life quality of patients. To develop effective treatment of cognitive deficits, it is important to understand their neurobiological causes and to identify potential therapeutic targets. In this study, adopting repeated MK-801 treatment as an animal model of schizophrenia, we investigated whether antipsychotic drugs, olanzapine and haloperidol, can reverse MK-801-induced cognitive deficits and how the reversal processes recruited proteins involved in glutamate neurotransmission in rat medial prefrontal cortex (mPFC) and hippocampus. We found that low-dose chronic MK-801 treatment impaired object-in-context recognition memory and reversal learning in the Morris water maze, leaving reference memory relatively unaffected, and that these cognitive deficits can be partially reversed by olanzapine, not haloperidol, treatment. At the molecular level, chronic MK-801 treatment resulted in the reduction of multiple N-methyl-D-aspartate (NMDA) receptor subunits in rat mPFC and olanzapine, not haloperidol, treatment restored the levels of GluN1 and phosphorylated GluN2B in this region. Taken together, MK-801-induced cognitive deficits may be associated with region-specific changes in NMDA receptor subunits and the reversal of specific NMDA receptor subunits may underlie the cognition-enhancing effects of olanzapine. PMID:29375333

Grammar predicts procedural learning and consolidation deficits in children with Specific Language Impairment.

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Hedenius, Martina; Persson, Jonas; Tremblay, Antoine; Adi-Japha, Esther; Veríssimo, João; Dye, Cristina D; Alm, Per; Jennische, Margareta; Bruce Tomblin, J; Ullman, Michael T

2011-01-01

The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have indeed reported procedural learning impairments in SLI, and have found that these are associated with grammatical difficulties. The present study extends this research by examining consolidation and longer-term procedural sequence learning in children with SLI. The Alternating Serial Reaction Time (ASRT) task was given to children with SLI and typically developing (TD) children in an initial learning session and an average of three days later to test for consolidation and longer-term learning. Although both groups showed evidence of initial sequence learning, only the TD children showed clear signs of consolidation, even though the two groups did not differ in longer-term learning. When the children were re-categorized on the basis of grammar deficits rather than broader language deficits, a clearer pattern emerged. Whereas both the grammar impaired and normal grammar groups showed evidence of initial sequence learning, only those with normal grammar showed consolidation and longer-term learning. Indeed, the grammar-impaired group appeared to lose any sequence knowledge gained during the initial testing session. These findings held even when controlling for vocabulary or a broad non-grammatical language measure, neither of which were associated with procedural memory. When grammar was examined as a continuous variable over all children, the same relationships between procedural memory and grammar, but not vocabulary or the broader language measure, were observed. Overall, the findings support and further specify the PDH. They suggest that consolidation and longer-term procedural learning are impaired in SLI, but that these

Grammar Predicts Procedural Learning and Consolidation Deficits in Children with Specific Language Impairment

Science.gov (United States)

Hedenius, Martina; Persson, Jonas; Tremblay, Antoine; Adi-Japha, Esther; Veríssimo, João; Dye, Cristina D.; Alm, Per; Jennische, Margareta; Tomblin, J. Bruce; Ullman, Michael T.

2011-01-01

The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have indeed reported procedural learning impairments in SLI, and have found that these are associated with grammatical difficulties. The present study extends this research by examining the consolidation and longer-term procedural sequence learning in children with SLI. The Alternating Serial Reaction Time (ASRT) task was given to children with SLI and typically-developing (TD) children in an initial learning session and an average of three days later to test for consolidation and longer-term learning. Although both groups showed evidence of initial sequence learning, only the TD children showed clear signs of consolidation, even though the two groups did not differ in longer-term learning. When the children were re-categorized on the basis of grammar deficits rather than broader language deficits, a clearer pattern emerged. Whereas both the grammar impaired and normal grammar groups showed evidence of initial sequence learning, only those with normal grammar showed consolidation and longer-term learning. Indeed, the grammar-impaired group appeared to lose any sequence knowledge gained during the initial testing session. These findings held even when controlling for vocabulary or a broad non-grammatical language measure, neither of which were associated with procedural memory. When grammar was examined as a continuous variable over all children, the same relationships between procedural memory and grammar, but not vocabulary or the broader language measure, were observed. Overall, the findings support and further specify the PDH. They suggest that consolidation and longer-term procedural learning are impaired in SLI, but that

Relative risk of probabilistic category learning deficits in patients with schizophrenia and their siblings

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Weickert, Thomas W.; Goldberg, Terry E.; Egan, Michael F.; Apud, Jose A.; Meeter, Martijn; Myers, Catherine E.; Gluck, Mark A; Weinberger, Daniel R.

2010-01-01

Background While patients with schizophrenia display an overall probabilistic category learning performance deficit, the extent to which this deficit occurs in unaffected siblings of patients with schizophrenia is unknown. There are also discrepant findings regarding probabilistic category learning acquisition rate and performance in patients with schizophrenia. Methods A probabilistic category learning test was administered to 108 patients with schizophrenia, 82 unaffected siblings, and 121 healthy participants. Results Patients with schizophrenia displayed significant differences from their unaffected siblings and healthy participants with respect to probabilistic category learning acquisition rates. Although siblings on the whole failed to differ from healthy participants on strategy and quantitative indices of overall performance and learning acquisition, application of a revised learning criterion enabling classification into good and poor learners based on individual learning curves revealed significant differences between percentages of sibling and healthy poor learners: healthy (13.2%), siblings (34.1%), patients (48.1%), yielding a moderate relative risk. Conclusions These results clarify previous discrepant findings pertaining to probabilistic category learning acquisition rate in schizophrenia and provide the first evidence for the relative risk of probabilistic category learning abnormalities in unaffected siblings of patients with schizophrenia, supporting genetic underpinnings of probabilistic category learning deficits in schizophrenia. These findings also raise questions regarding the contribution of antipsychotic medication to the probabilistic category learning deficit in schizophrenia. The distinction between good and poor learning may be used to inform genetic studies designed to detect schizophrenia risk alleles. PMID:20172502

Mechanism and treatment for the learning and memory deficits associated with mouse models of Noonan syndrome

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Lee, Yong-Seok; Ehninger, Dan; Zhou, Miou; Oh, Jun-Young; Kang, Minkyung; Kwak, Chuljung; Ryu, Hyun-Hee; Butz, Delana; Araki, Toshiyuki; Cai, Ying; Balaji, J.; Sano, Yoshitake; Nam, Christine I.; Kim, Hyong Kyu; Kaang, Bong-Kiun; Burger, Corinna; Neel, Benjamin G.; Silva, Alcino J.

2015-01-01

In Noonan Syndrome (NS) 30% to 50% of subjects show cognitive deficits of unknown etiology and with no known treatment. Here, we report that knock-in mice expressing either of two NS-associated Ptpn11 mutations show hippocampal-dependent spatial learning impairments and deficits in hippocampal long-term potentiation (LTP). In addition, viral overexpression of the PTPN11D61G in adult hippocampus results in increased baseline excitatory synaptic function, deficits in LTP and spatial learning, which can all be reversed by a MEK inhibitor. Furthermore, brief treatment with lovastatin reduces Ras-Erk activation in the brain, and normalizes the LTP and learning deficits in adult Ptpn11D61G/+ mice. Our results demonstrate that increased basal Erk activity and corresponding baseline increases in excitatory synaptic function are responsible for the LTP impairments and, consequently, the learning deficits in mouse models of NS. These data also suggest that lovastatin or MEK inhibitors may be useful for treating the cognitive deficits in NS. PMID:25383899

Chronic caffeine exposure attenuates blast-induced memory deficit in mice.

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Ning, Ya-Lei; Yang, Nan; Chen, Xing; Zhao, Zi-Ai; Zhang, Xiu-Zhu; Chen, Xing-Yun; Li, Ping; Zhao, Yan; Zhou, Yuan-Guo

2015-01-01

To investigate the effects of three different ways of chronic caffeine administration on blast- induced memory dysfunction and to explore the underlying mechanisms. Adult male C57BL/6 mice were used and randomly divided into five groups: control: without blast exposure, con-water: administrated with water continuously before and after blast-induced traumatic brain injury (bTBI), con-caffeine: administrated with caffeine continuously for 1 month before and after bTBI, pre-caffeine: chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI, post-caffeine: chronically administrated with caffeine after bTBI. After being subjected to moderate intensity of blast injury, mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1, 4, and 8 weeks post-blast injury. Neurological deficit scoring, glutamate concentration, proinflammatory cytokines production, and neuropathological changes at 24 h, 1, 4, and 8 weeks post-bTBI were examined to evaluate the brain injury in early and prolonged stages. Adenosine A1 receptor expression was detected using qPCR. All of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit, which is correlated with the neuroprotective effects against excitotoxicity, inflammation, astrogliosis and neuronal loss at different stages of injury. Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI; pre-bTBI and post-bTBI treatment of caffeine tended to exert neuroprotective effects at early and prolonged stages of bTBI respectively. Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption. Since caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get, the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.

Effectiveness of Memantine in Improvement of Cognitive Deficits in Specific Learning Disorder

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Elham Ahmadi Zahrani

2016-12-01

Full Text Available Abstract Background: Specific learning disorder is a neurodevelopmental disorder characterized by persistent difficulties in learning academic skills in reading, written expression, or mathematics. This study was performed to investigate the effectiveness of memantine in the relief of cognitive deficits (selective attention, sustained attention, and working memory in specific learning disorder. Materials and Methods: This study is a clinical trial. Of all children 8-12 years referred to Amir Kabir Hospital 94 patients diagnosed with specific learning disorder based on DSMV diagnostic interview referred by specialist and randomly divided by two groups, memantine and placebo. Cognitive deficits before and after treatment were measured with continuous performance test, Stroop test and Wechsler Digit Span forward and reverse and Corsi test. Results: Multivariate analysis of variance showed a significant difference in error when answering, omission answer and corrected answer in continuous performance test, but this difference is not significant in response time. Difference in forward, reverse and collected auditory was significant and not significant in the auditory span. In active visual working memory at corsi cube test, difference was significant (p <0.05. Conclusion: The results showed that memantine in improvement of sustained attention, auditory working memory and visual working memory, is effective, while in selective attention is not effective and according to similarities of learning disorder and Attention deficit / Hyperactivity disorder (ADHD and the effectiveness of memantine in improvement of symptoms of ADHD, we can also use this drug in improvement of cognitive deficits of specific learning disorder.

Chronic voluntary oral methamphetamine induces deficits in spatial learning and hippocampal protein kinase Mzeta with enhanced astrogliosis and cyclooxygenase-2 levels

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Jorge A. Avila

2018-02-01

Full Text Available Methamphetamine (MA is an addictive drug with neurotoxic effects on the brain producing cognitive impairment and increasing the risk for neurodegenerative disease. Research has focused largely on examining the neurochemical and behavioral deficits induced by injecting relatively high doses of MA [30 mg/kg of body weight (bw] identifying the upper limits of MA-induced neurotoxicity. Accordingly, we have developed an appetitive mouse model of voluntary oral MA administration (VOMA based on the consumption of a palatable sweetened oatmeal mash containing a known amount of MA. This VOMA model is useful for determining the lower limits necessary to produce neurotoxicity in the short-term and long-term as it progresses over time. We show that mice consumed on average 1.743 mg/kg bw/hour during 3 hours, and an average of 5.23 mg/kg bw/day over 28 consecutive days on a VOMA schedule. Since this consumption rate is much lower than the neurotoxic doses typically injected, we assessed the effects of long-term chronic VOMA on both spatial memory performance and on the levels of neurotoxicity in the hippocampus. Following 28 days of VOMA, mice exhibited a significant deficit in short-term spatial working memory and spatial reference learning on the radial 8-arm maze (RAM compared to controls. This was accompanied by a significant decrease in memory markers protein kinase Mzeta (PKMζ, calcium impermeable AMPA receptor subunit GluA2, and the post-synaptic density 95 (PSD-95 protein in the hippocampus. Compared to controls, the VOMA paradigm also induced decreases in hippocampal levels of dopamine transporter (DAT and tyrosine hydroxylase (TH, as well as increases in dopamine 1 receptor (D1R, glial fibrillary acidic protein (GFAP and cyclooxygenase-2 (COX-2, with a decrease in prostaglandins E2 (PGE2 and D2 (PGD2. These results demonstrate that chronic VOMA reaching 146 mg/kg bw/28d induces significant hippocampal neurotoxicity. Future studies will evaluate

Growth hormone releasing hormone (GHRH) signaling modulates intermittent hypoxia-induced oxidative stress and cognitive deficits in mouse.

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Nair, Deepti; Ramesh, Vijay; Li, Richard C; Schally, Andrew V; Gozal, David

2013-11-01

Intermittent hypoxia (IH) during sleep, such as occurs in obstructive sleep apnea (OSA), leads to degenerative changes in the hippocampus, and is associated with spatial learning deficits in adult mice. In both patients and murine models of OSA, the disease is associated with suppression of growth hormone (GH) secretion, which is actively involved in the growth, development, and function of the central nervous system (CNS). Recent work showed that exogenous GH therapy attenuated neurocognitive deficits elicited by IH during sleep in rats. Here, we show that administration of the Growth Hormone Releasing Hormone (GHRH) agonist JI-34 attenuates IH-induced neurocognitive deficits, anxiety, and depression in mice along with reduction in oxidative stress markers such as MDA and 8-hydroxydeoxyguanosine, and increases in hypoxia inducible factor-1α DNA binding and up-regulation of insulin growth factor-1 and erythropoietin expression. In contrast, treatment with a GHRH antagonist (MIA-602) during intermittent hypoxia did not affect any of the IH-induced deleterious effects in mice. Thus, exogenous GHRH administered as the formulation of a GHRH agonist may provide a viable therapeutic intervention to protect IH-vulnerable brain regions from OSA-associated neurocognitive dysfunction. Sleep apnea, characterized by chronic intermittent hypoxia (IH), is associated with substantial cognitive and behavioral deficits. Here, we show that administration of a GHRH agonist (JI-34) reduces oxidative stress, increases both HIF-1α nuclear binding and downstream expression of IGF1 and erythropoietin (EPO) in hippocampus and cortex, and markedly attenuates water maze performance deficits in mice exposed to intermittent hypoxia during sleep. © 2013 International Society for Neurochemistry.

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

Sequence-specific procedural learning deficits in children with specific language impairment.

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Hsu, Hsinjen Julie; Bishop, Dorothy V M

2014-05-01

This study tested the procedural deficit hypothesis of specific language impairment (SLI) by comparing children's performance in two motor procedural learning tasks and an implicit verbal sequence learning task. Participants were 7- to 11-year-old children with SLI (n = 48), typically developing age-matched children (n = 20) and younger typically developing children matched for receptive grammar (n = 28). In a serial reaction time task, the children with SLI performed at the same level as the grammar-matched children, but poorer than age-matched controls in learning motor sequences. When tested with a motor procedural learning task that did not involve learning sequential relationships between discrete elements (i.e. pursuit rotor), the children with SLI performed comparably with age-matched children and better than younger grammar-matched controls. In addition, poor implicit learning of word sequences in a verbal memory task (the Hebb effect) was found in the children with SLI. Together, these findings suggest that SLI might be characterized by deficits in learning sequence-specific information, rather than generally weak procedural learning. © 2014 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

Isorhynchophylline improves learning and memory impairments induced by D-galactose in mice.

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Xian, Yan-Fang; Su, Zi-Ren; Chen, Jian-Nan; Lai, Xiao-Ping; Mao, Qing-Qiu; Cheng, Christopher H K; Ip, Siu-Po; Lin, Zhi-Xiu

2014-10-01

Isorhynchophylline (IRN), an alkaloid isolated from Uncaria rhynchophylla, has been reported to improve cognitive impairment induced by beta-amyloid in rats. However, whether IRN could also ameliorate the D-galactose (D-gal)-induced mouse memory deficits is still not clear. In the present study, we aimed to investigate whether IRN had potential protective effect against the D-gal-induced cognitive deficits in mice. Mice were given a subcutaneous injection of D-gal (100mg/kg) and orally administered IRN (20 or 40mg/kg) daily for 8weeks, followed by assessing spatial learning and memory function by the Morris water maze test. The results showed that IRN significantly improved spatial learning and memory function in the D-gal-treated mice. In the mechanistic studies, IRN significantly increased the level of glutathione (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT), while decreased the level of malondialdehyde (MDA) in the brain tissues of the D-gal-treated mice. Moreover, IRN (20 or 40mg/kg) significantly inhibited the production of prostaglandin E 2 (PGE2) and nitric oxide (NO), and the mRNA expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), as well as the activation of nuclear factor kappa B (NF-κB) in the brain tissues of D-gal-treated mice. Our results amply demonstrated that IRN was able to ameliorate cognitive deficits induced by D-gal in mice, and the observed cognition-improving action may be mediated, at least in part, through enhancing the antioxidant status and anti-inflammatory effect of brain tissues via NFκB signaling. Copyright © 2014 Elsevier Ltd. All rights reserved.

Postconditioning with sevoflurane ameliorates spatial learning and memory deficit via attenuating endoplasmic reticulum stress induced neuron apoptosis in a rat model of hemorrhage shock and resuscitation.

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Hu, Xianwen; Wang, Jingxian; Zhang, Li; Zhang, Qiquan; Duan, Xiaowen; Zhang, Ye

2018-06-02

Hemorrhage shock could initiate endoplasmic reticulum stress (ERS) and then induce neuronal apoptosis. The aim of this study was to investigate whether sevoflurane postconditioning could attenuate brain injury via suppressing apoptosis induced by ERS. Seventy male rats were randomized into five groups: sham, shock, low concentration (sevo1, 1.2%), middle concentration (sevo2, 2.4%) and high concentration (sevo3, 3.6%) of sevoflurane postconditioning. Hemorrhage shock was induced by removing 40% of the total blood volume during an interval of 30 min. 1h after the completion of bleeding, the animals were reinfused with shed blood during the ensuing 30 min. The spatial learning and memory ability of rats were measured by Morris water maze (MWM) test three days after the operation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region were assessed after the MWM test. The expression of C/EBP-homologousprotein (CHOP) and glucose-regulated protein 78 (GRP78) in the hippocampus were measured at 24h after reperfusion. We found that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% significantly ameliorated the spatial learning and memory ability, decreased the TUNEL-positive cells, and reduced the GRP78 and CHOP expression compared with the shock group. These results suggested that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% could ameliorate spatial learning and memory deficit after hemorrhage shock and resuscitation injury via suppressing apoptosis induced by ERS. Copyright © 2018. Published by Elsevier B.V.

Hyperoside protects against chronic mild stress-induced learning and memory deficits.

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Gong, Yeli; Yang, Youhua; Chen, Xiaoqing; Yang, Min; Huang, Dan; Yang, Rong; Zhou, Lianying; Li, Changlei; Xiong, Qiuju; Xiong, Zhe

2017-07-01

Hyperoside (quercetin-3-O-b-d-galactosidepyranose) is a plant-derived flavonoid mainly found in fruits, fruit juices (most notably flavanols, flavanones, and anthocyanins) and Chinese traditional medicines. It has been applied to relieve pain and improve cardiovascular functions in clinic. However, the effects of hyperoside on cognitive impairment induced by chronic stress and the underlying molecular mechanisms remain unclear. In the current study, we used chronic mild stress (CMS) rats to investigate the effects of hyperoside on learning and memory and further explore the possible mechanisms. Our results demonstrated that hyperoside reduced the escape latency and the swimming distance of CMS rats in Morris water maze test and reversed depressive symptoms in forced swim test (FST) and sucrose preference test. In addition, hyperoside increased the expression of brain-derived neurotrophic factor (BDNF) in hippocampus of CMS rats without influencing the corticosterone (CORT) level in blood plasma. Furthermore, K252a, an inhibitor of the BDNF receptor TrkB, prevented the protective effects of hyperoside on learning and memory in CMS rats. Taken together, these results indicate that hyperoside reverses the cognitive impairment induced by CMS, which is associated with the regulation of BDNF signaling pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Icariin Attenuates Synaptic and Cognitive Deficits in an Aβ1–42-Induced Rat Model of Alzheimer’s Disease

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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.

Whole brain radiation-induced impairments in learning and memory are time-sensitive and reversible by systemic hypoxia.

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Junie P Warrington

Full Text Available 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.

High protein diet maintains glucose production during exercise-induced energy deficit: a controlled trial

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Inadequate energy intake induces changes in endogenous glucose production (GP) to preserve muscle mass. Whether addition provision of dietary protein modulates GP response to energy deficit is unclear. The objective was to determine whether exercise-induced energy deficit effects on glucose metaboli...

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.

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.  

Counselling for Facilitating Learning for the Attention – Deficit ...

African Journals Online (AJOL)

The study investigated the extent of counsellor's identification of the symptoms of attention-deficit/hyperactivity disorder and the counselling strategies the counsellors use to facilitate learning for such learners. Two research questions and two hypotheses guided the study. The design of the study was survey. The area of the ...

A Benefit/Cost/Deficit (BCD) model for learning from human errors

International Nuclear Information System (INIS)

Vanderhaegen, Frederic; Zieba, Stephane; Enjalbert, Simon; Polet, Philippe

2011-01-01

This paper proposes an original model for interpreting human errors, mainly violations, in terms of benefits, costs and potential deficits. This BCD model is then used as an input framework to learn from human errors, and two systems based on this model are developed: a case-based reasoning system and an artificial neural network system. These systems are used to predict a specific human car driving violation: not respecting the priority-to-the-right rule, which is a decision to remove a barrier. Both prediction systems learn from previous violation occurrences, using the BCD model and four criteria: safety, for identifying the deficit or the danger; and opportunity for action, driver comfort, and time spent; for identifying the benefits or the costs. The application of learning systems to predict car driving violations gives a rate over 80% of correct prediction after 10 iterations. These results are validated for the non-respect of priority-to-the-right rule.

Motor skill learning, retention, and control deficits in Parkinson's disease.

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Lisa Katharina Pendt

Full Text Available Parkinson's disease, which affects the basal ganglia, is known to lead to various impairments of motor control. Since the basal ganglia have also been shown to be involved in learning processes, motor learning has frequently been investigated in this group of patients. However, results are still inconsistent, mainly due to skill levels and time scales of testing. To bridge across the time scale problem, the present study examined de novo skill learning over a long series of practice sessions that comprised early and late learning stages as well as retention. 19 non-demented, medicated, mild to moderate patients with Parkinson's disease and 19 healthy age and gender matched participants practiced a novel throwing task over five days in a virtual environment where timing of release was a critical element. Six patients and seven control participants came to an additional long-term retention testing after seven to nine months. Changes in task performance were analyzed by a method that differentiates between three components of motor learning prominent in different stages of learning: Tolerance, Noise and Covariation. In addition, kinematic analysis related the influence of skill levels as affected by the specific motor control deficits in Parkinson patients to the process of learning. As a result, patients showed similar learning in early and late stages compared to the control subjects. Differences occurred in short-term retention tests; patients' performance constantly decreased after breaks arising from poorer release timing. However, patients were able to overcome the initial timing problems within the course of each practice session and could further improve their throwing performance. Thus, results demonstrate the intact ability to learn a novel motor skill in non-demented, medicated patients with Parkinson's disease and indicate confounding effects of motor control deficits on retention performance.

Effects of Compound Yi-Zhi on D-galactose-induced learning and memory deficits in mice

Institute of Scientific and Technical Information of China (English)

XUJiang-Ping; WUHang-Yu; LILin

2004-01-01

AIM: To explore the effects of Compound Yi-Zhi (YZC) on learning and memory capacity and free radical metabolism in D-galactose induced mice dementia model. METHODS: The mice dementia model was induced by a daily D-galactose 0.15g/kg sc for 45 days and after 5 days'D-galactose injection, the mice were treated with three doses of YZC

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

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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 attention-deficit/hyperactivity disorder only group, there were no 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

Feedback-based probabilistic category learning is selectively impaired in attention/hyperactivity deficit disorder.

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Gabay, Yafit; Goldfarb, Liat

2017-07-01

Although Attention-Deficit Hyperactivity Disorder (ADHD) is closely linked to executive function deficits, it has recently been attributed to procedural learning impairments that are quite distinct from the former. These observations challenge the ability of the executive function framework solely to account for the diverse range of symptoms observed in ADHD. A recent neurocomputational model emphasizes the role of striatal dopamine (DA) in explaining ADHD's broad range of deficits, but the link between this model and procedural learning impairments remains unclear. Significantly, feedback-based procedural learning is hypothesized to be disrupted in ADHD because of the involvement of striatal DA in this type of learning. In order to test this assumption, we employed two variants of a probabilistic category learning task known from the neuropsychological literature. Feedback-based (FB) and paired associate-based (PA) probabilistic category learning were employed in a non-medicated sample of ADHD participants and neurotypical participants. In the FB task, participants learned associations between cues and outcomes initially by guessing and subsequently through feedback indicating the correctness of the response. In the PA learning task, participants viewed the cue and its associated outcome simultaneously without receiving an overt response or corrective feedback. In both tasks, participants were trained across 150 trials. Learning was assessed in a subsequent test without a presentation of the outcome or corrective feedback. Results revealed an interesting disassociation in which ADHD participants performed as well as control participants in the PA task, but were impaired compared with the controls in the FB task. The learning curve during FB training differed between the two groups. Taken together, these results suggest that the ability to incrementally learn by feedback is selectively disrupted in ADHD participants. These results are discussed in relation to both

Relationship between Learning Problems and Attention Deficit in Childhood

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Ponde, Milena Pereira; Cruz-Freire, Antonio Carlos; Silveira, Andre Almeida

2012-01-01

Objective: To assess the impact of attention deficit on learning problems in a sample of schoolchildren in the city of Salvador, Bahia, Brazil. Method: All students enrolled in selected elementary schools were included in this study, making a total of 774 children. Each child was assessed by his or her teacher using a standardized scale. "The…

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

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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.

Effects of the selective 5-HT7 receptor antagonist SB-269970 and amisulpride on ketamine-induced schizophrenia-like deficits in rats.

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Agnieszka Nikiforuk

Full Text Available A wide body of evidence suggests that 5-HT7 receptors are implicated in a variety of central nervous system functions, including control of learning and memory processes. According to recent preclinical data, the selective blockade of these receptors may be a potential target for cognitive improvement in schizophrenia. The first aim of the present study was to evaluate the effects of the selective 5-HT7 receptor antagonist, SB-269970, and the antipsychotic drug with a high affinity for 5-HT7 receptors, amisulpride, on ketamine-induced deficits in attentional set-shifting and novel object recognition tasks in rats. Because the role of 5-HT7 receptor blockade in ameliorating positive and negative symptoms of schizophrenia remains equivocal, the second aim of these experiments was to examine the effectiveness of SB-269970 and amisulpride in reversing ketamine-induced deficits in prepulse inhibition of the startle reflex and in social interaction test in rats. The study revealed that acute administration of SB-269970 (1 mg/kg or amisulpride (3 mg/kg ameliorated ketamine-induced cognitive inflexibility and novel object recognition deficit in rats. Both compounds were also effective in attenuating ketamine-evoked disruption of social interactions. In contrast, neither SB-269970 nor amisulpride affected ketamine-disrupted prepulse inhibition or 50 kHz USVs accompanying social behaviour. In conclusion, antagonism of 5-HT7 receptors may represent a useful pharmacological approach in the treatment of cognitive deficits and some negative symptoms of schizophrenia.

Therapeutic Efficacy of Fenugreek Extract or/and Choline with Docosahexaenoic Acid in Attenuating Learning and Memory Deficits in Ovariectomized Rats

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Anjaneyulu K

2018-04-01

Full Text Available Background: Studies have demonstrated that estradiol influences cognitive functions. Phytoestrogens and many other estrogen-like compounds in plants have beneficial effects on cognitive performance in postmenopausal women. However, there is no evident report of fenugreek and choline-Docosahexaenoic Acid (DHA on cognition in ovariectomized rats. Aim and Objectives: The present study was aimed to evaluate the therapeutic efficacy of fenugreek extract or/and choline- DHA in attenuating ovariectomy-induced memory impairment, brain antioxidant status and hippocampal neural cell deficits in the rat model. Material and Methods: Female Wistar 9-10 months old rats were grouped (n=12/group as - (1 Normal Control (NC, (2 Ovariectomized (OVX, (3 OVX+FG (hydroalcoholic seed extract of fenugreek, (4 OVX+C-DHA,(5 OVX+FG+C-DHA and (6 OVX+Estradiol. Groups 2- 6 were bilaterally OVX. FG, C-DHA was supplemented orally for 30 days, 14 days after ovariectomy. Assessment of learning and memory was performed by passive avoidance test. Oxidative stress and antioxidant markers were assessed by standard methods. Nissl stained hippocampal sections were analyzed to determine alterations in neural cell numbers in CA1, CA3 and dentate gyrus. Results: Supplementation of FG or/and choline with DHA to OVX rats, caused significant improvement in learning and memory as well as decreased neural cell deficits compared to the same in OVX rats. Further, significantly reduced levels of brain Malondialdehyde (MDA and increased levels of Glutathione (GSH were observed. Conclusion: Therapeutic supplementation of FG with choline-DHA significantly attenuates ovariectomy-induced neurocognitive deficits in rats.

Visual and verbal learning deficits in Veterans with alcohol and substance use disorders.

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Bell, Morris D; Vissicchio, Nicholas A; Weinstein, Andrea J

2016-02-01

This study examined visual and verbal learning in the early phase of recovery for 48 Veterans with alcohol use (AUD) and substance use disorders (SUD, primarily cocaine and opiate abusers). Previous studies have demonstrated visual and verbal learning deficits in AUD, however little is known about the differences between AUD and SUD on these domains. Since the DSM-5 specifically identifies problems with learning in AUD and not in SUD, and problems with visual and verbal learning have been more prevalent in the literature for AUD than SUD, we predicted that people with AUD would be more impaired on measures of visual and verbal learning than people with SUD. Participants were enrolled in a comprehensive rehabilitation program and were assessed within the first 5 weeks of abstinence. Verbal learning was measured using the Hopkins Verbal Learning Test (HVLT) and visual learning was assessed using the Brief Visuospatial Memory Test (BVMT). Results indicated significantly greater decline in verbal learning on the HVLT across the three learning trials for AUD participants but not for SUD participants (F=4.653, df=48, p=0.036). Visual learning was less impaired than verbal learning across learning trials for both diagnostic groups (F=0.197, df=48, p=0.674); there was no significant difference between groups on visual learning (F=0.401, df=14, p=0.538). Older Veterans in the early phase of recovery from AUD may have difficulty learning new verbal information. Deficits in verbal learning may reduce the effectiveness of verbally-based interventions such as psycho-education. Published by Elsevier Ireland Ltd.

Neurogenic Stuttering and Lateralized Motor Deficits Induced by Tranylcypromine

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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.

Nutritional compensation to exercise- vs. diet-induced acute energy deficit in adolescents with obesity.

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Thivel, David; Doucet, Eric; Julian, Valérie; Cardenoux, Charlotte; Boirie, Yves; Duclos, Martine

2017-07-01

To compare the energy and macronutrient intake responses to equivalent energy deficits induced by diet (food restriction) and exercise in adolescents with obesity. Fourteen 12-15years old obese adolescents completed three experimental conditions (08:00am to 07:30pm) in a randomized crossover design: i) control session (CON); ii) diet-induced 25% energy depletion (Def-EI), iii) and an exercise-induced 25% energy depletion (Def-EX). The sessions order was either CON/Def-EI/Def-EX or CON/Def-EX/Def-EI as the deficit corresponded to 25% of the energy ingested at lunch on the control day (CON) and was imposed either by exercise (Def-EX) or diet (Def-EI). Ad libitum EI and macronutrients preferences were assessed at dinner and appetite sensations assessed using visual analogue scales. Mean BMI was 36.6±5.0kg/m 2 (z-BMI: 2.40±0.29). The individually calibrated 25% energy deficit represented 254±92kcal. Ad libitum EI was significantly higher during both Def-EX (971±225kcal) and Def-EI (949±246kcal) compared with CON (742±297) (pexercise and the control session (EI Def-EX - EI CON) (r=-0,643 pexercise- or diet-induced energy deficits could lead to similar EI compensation in obese adolescents but this EI compensation might be influenced by the magnitude of the deficit. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative Deficits of Preschool Children at Risk for Mathematical Learning Disability

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Felicia W. Chu

2013-05-01

Full Text Available The study tested the hypothesis that acuity of the potentially inherent approximate number system (ANS contributes to risk of mathematical learning disability (MLD. Sixty-eight (35 boys preschoolers at risk for school failure were assessed on a battery of quantitative tasks, and on intelligence, executive control, preliteracy skills, and parental education. Mathematics achievement scores at the end of one year of preschool indicated that 34 of these children were at high risk for MLD. Relative to the 34 typically achieving children, the at risk children were less accurate on the ANS task, and a one standard deviation deficit on this task resulted in a 2.4 fold increase in the odds of MLD status. The at risk children also had a poor understanding of ordinal relations, and had slower learning of Arabic numerals, number words, and their cardinal values. Poor performance on these tasks resulted in 3.6 to 4.5 fold increases in the odds of MLD status. The results provide some support for the ANS hypothesis but also suggest these deficits are not the primary source of poor mathematics learning.

A tribute to Charlie Chaplin: Induced positive affect improves reward-based decision-learning in Parkinson’s Disease

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K. Richard eRidderinkhof

2012-06-01

Full Text Available Reward-based decision-learning refers to the process of learning to select those actions that lead to rewards while avoiding actions that lead to punishments. This process, known to rely on dopaminergic activity in striatal brain regions, is compromised in Parkinson’s disease (PD. We hypothesized that such decision-learning deficits are alleviated by induced positive affect, which is thought to incur transient boosts in midbrain and striatal dopaminergic activity. Computational measures of probabilistic reward-based decision-learning were determined for 51 patients diagnosed with PD. Previous work has shown these measures to rely on the nucleus caudatus (outcome evaluation during the early phases of learning and the putamen (reward prediction during later phases of learning. We observed that induced positive affect facilitated learning, through its effects on reward prediction rather than outcome evaluation. Viewing a few minutes of comedy clips served to remedy dopamine-related problems in putamen-based frontostriatal circuitry and, consequently, in learning to predict which actions will yield reward.

Chronic 5-HT4 receptor agonist treatment restores learning and memory deficits in a neuroendocrine mouse model of anxiety/depression.

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Darcet, Flavie; Gardier, Alain M; David, Denis J; Guilloux, Jean-Philippe

2016-03-11

Cognitive disturbances are often reported as serious invalidating symptoms in patients suffering from major depression disorders (MDD) and are not fully corrected by classical monoaminergic antidepressant drugs. If the role of 5-HT4 receptor agonists as cognitive enhancers is well established in naïve animals or in animal models of cognitive impairment, their cognitive effects in the context of stress need to be examined. Using a mouse model of anxiety/depression (CORT model), we reported that a chronic 5-HT4 agonist treatment (RS67333, 1.5mg/kg/day) restored chronic corticosterone-induced cognitive deficits, including episodic-like, associative and spatial learning and memory impairments. On the contrary, a chronic monoaminergic antidepressant drug treatment with fluoxetine (18mg/kg/day) only partially restored spatial learning and memory deficits and had no effect in the associative/contextual task. These results suggest differential mechanisms underlying cognitive effects of these drugs. Finally, the present study highlights 5-HT4 receptor stimulation as a promising therapeutic mechanism to alleviate cognitive symptoms related to MDD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Neuroleptic-induced deficit syndrome in bipolar disorder with psychosis

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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

The role of trigeminal nucleus caudalis orexin 1 receptors in orofacial pain transmission and in orofacial pain-induced learning and memory impairment in rats.

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Kooshki, Razieh; Abbasnejad, Mehdi; Esmaeili-Mahani, Saeed; Raoof, Maryam

2016-04-01

It is widely accepted that the spinal trigeminal nuclear complex, especially the subnucleus caudalis (Vc), receives input from orofacial structures. The neuropeptides orexin-A and -B are expressed in multiple neuronal systems. Orexin signaling has been implicated in pain-modulating system as well as learning and memory processes. Orexin 1 receptor (OX1R) has been reported in trigeminal nucleus caudalis. However, its roles in trigeminal pain modulation have not been elucidated so far. This study was designed to investigate the role of Vc OX1R in the modulation of orofacial pain as well as pain-induced learning and memory deficits. Orofacial pain was induced by subcutaneous injection of capsaicin in the right upper lip of the rats. OX1R agonist (orexin-A) and antagonist (SB-334867-A) were microinjected into Vc prior capsaicin administration. After recording nociceptive times, learning and memory was investigated using Morris water maze (MWM) test. The results indicated that, orexin-A (150 pM/rat) significantly reduced the nociceptive times, while SB334867-A (80 nM/rat) exaggerated nociceptive behavior in response to capsaicin injection. In MWM test, capsaicin-treated rats showed a significant learning and memory impairment. Moreover, SB-334867-A (80 nM/rat) significantly exaggerated learning and memory impairment in capsaicin-treated rats. However, administration of orexin-A (100 pM/rat) prevented learning and memory deficits. Taken together, these results indicate that Vc OX1R was at least in part involved in orofacial pain transmission and orexin-A has also a beneficial inhibitory effect on orofacial pain-induced deficits in abilities of spatial learning and memory. Copyright © 2016 Elsevier Inc. All rights reserved.

Deficits in water maze performance and oxidative stress in the hippocampus and striatum induced by extremely low frequency magnetic field exposure.

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Yonghua Cui

Full Text Available The exposures to extremely low frequency magnetic field (ELF-MF in our environment have dramatically increased. Epidemiological studies suggest that there is a possible association between ELF-MF exposure and increased risks of cardiovascular disease, cancers and neurodegenerative disorders. Animal studies show that ELF-MF exposure may interfere with the activity of brain cells, generate behavioral and cognitive disturbances, and produce deficits in attention, perception and spatial learning. Although, many research efforts have been focused on the interaction between ELF-MF exposure and the central nervous system, the mechanism of interaction is still unknown. In this study, we examined the effects of ELF-MF exposure on learning in mice using two water maze tasks and on some parameters indicative of oxidative stress in the hippocampus and striatum. We found that ELF-MF exposure (1 mT, 50 Hz induced serious oxidative stress in the hippocampus and striatum and impaired hippocampal-dependent spatial learning and striatum-dependent habit learning. This study provides evidence for the association between the impairment of learning and the oxidative stress in hippocampus and striatum induced by ELF-MF exposure.

Reversal of haloperidol induced motor deficits in rats exposed to repeated immobilization stress.

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Shireen, Erum; Pervez, Sidra; Masroor, Maria; Ali, Wafa Binte; Rais, Qudsia; Khalil, Samira; Tariq, Anum; Haleem, Darakshan Jabeen

2014-09-01

Stress is defined as a non specific response of body to any physiological and psychological demand. Preclinical studies have shown that an uncontrollable stress condition produces neurochemical and behavioral deficits. The present study was conducted to test the hypothesis that a decrease in the responsiveness of somatodendritic 5-hydroxytryptamine (5-HT)-1A receptors following adaptation to stress could attenuate haloperidol induced acute parkinsonian like effect. Results showed that single exposure (2h) to immobilization stress markedly decreased food intake, growth rate and locomotor activity but these stress-induced behavioral deficits were not observed following repeated (2h/day for 5 days) exposure of immobilization stress suggesting behavioral tolerance occurs to similar stress. An important finding of present study is a reversal of haloperidol-induced motor deficits in animals exposed to repeated immobilization stress than respective control animals. It is suggested that stress induced possible desensitization of somatodendritic 5-HT-1A as well as 5-HT-2C receptors could release dopamine system from the inhibitory influence of serotonin. On the other hand, an increase in the effectiveness of postsynaptic 5-HT-1A receptors elicits a direct stimulatory influence on the activity of dopaminergic neuron and is possibly involved in the reversal of haloperidol-induced parkinsonian like symptoms in repeatedly immobilized rats.

Contribution of organizational strategy to verbal learning and memory in adults with attention-deficit/hyperactivity disorder.

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Roth, Robert M; Wishart, Heather A; Flashman, Laura A; Riordan, Henry J; Huey, Leighton; Saykin, Andrew J

2004-01-01

Statistical mediation modeling was used to test the hypothesis that poor use of a semantic organizational strategy contributes to verbal learning and memory deficits in adults with attention-deficit/hyperactivity disorder (ADHD). Comparison of 28 adults with ADHD and 34 healthy controls revealed lower performance by the ADHD group on tests of verbal learning and memory, sustained attention, and use of semantic organization during encoding. Mediation modeling indicated that state anxiety, but not semantic organization, significantly contributed to the prediction of both learning and delayed recall in the ADHD group. The pattern of findings suggests that decreased verbal learning and memory in adult ADHD is due in part to situational anxiety and not to poor use of organizational strategies during encoding. ((c) 2004 APA, all rights reserved)

Improvement of dizocilpine-induced social recognition deficits in mice by brexpiprazole, a novel serotonin-dopamine activity modulator.

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Yoshimi, Noriko; Futamura, Takashi; Hashimoto, Kenji

2015-03-01

Cognitive impairment, including impaired social cognition, is largely responsible for the deterioration in social life suffered by patients with psychiatric disorders, such as schizophrenia and major depressive disorder (MDD). Brexpiprazole (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one), a novel serotonin-dopamine activity modulator, was developed to offer efficacious and tolerable therapy for different psychiatric disorders, including schizophrenia and adjunctive treatment of MDD. In this study, we investigated whether brexpiprazole could improve social recognition deficits (one of social cognition deficits) in mice, after administration of the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine). Dosing with dizocilpine (0.1mg/kg) induced significant impairment of social recognition in mice. Brexpiprazole (0.01, 0.03, 0.1mg/kg, p.o.) significantly ameliorated dizocilpine-induced social recognition deficits, without sedation or a reduction of exploratory behavior. In addition, brexpiprazole alone had no effect on social recognition in untreated control mice. By contrast, neither risperidone (0.03mg/kg, p.o.) nor olanzapine (0.03mg/kg, p.o.) altered dizocilpine-induced social recognition deficits. Finally, the effect of brexpiprazole on dizocilpine-induced social recognition deficits was antagonized by WAY-100,635, a selective serotonin 5-HT1A antagonist. These results suggest that brexpiprazole could improve dizocilpine-induced social recognition deficits via 5-HT1A receptor activation in mice. Therefore, brexpiprazole may confer a beneficial effect on social cognition deficits in patients with psychiatric disorders. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Contingency learning deficits and generalization in chronic unilateral hand pain patients.

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Meulders, Ann; Harvie, Daniel S; Bowering, Jane K; Caragianis, Suzanne; Vlaeyen, Johan W S; Moseley, G Lorimer

2014-10-01

Contingency learning, in particular the formation of danger beliefs, underpins conditioned fear and avoidance behavior, yet equally important is the formation of safety beliefs. That is, when threat beliefs and accompanying fear/avoidance spread to technically safe cues, it might cause disability. Indeed, such over generalization has been advanced as a trans-diagnostic pathologic marker, but it has not been investigated in chronic pain. Using a novel hand pain scenario contingency learning task, we tested the hypotheses that chronic hand pain patients demonstrate less differential pain expectancy judgments because of poor safety learning and demonstrate broader generalization gradients than healthy controls. Participants viewed digitized 3-dimensional hands in different postures presented in random order (conditioned stimulus [CS]) and rated the likelihood that a fictive patient would feel pain when moving the hand into that posture. Subsequently, the outcome (pain/no pain) was presented on the screen. One hand posture was followed by pain (CS+), another was not (CS-). Generalization was tested using novel hand postures (generalization stimuli) that varied in how similar they were to the original conditioned stimuli. Patients, but not healthy controls, demonstrated a contingency learning deficit determined by impaired safety learning, but not by exaggerated pain expectancy toward the CS+. Patients showed flatter, asymmetric generalization gradients than the healthy controls did, with higher pain expectancy for novel postures that were more similar to the original CS-. The results clearly uphold our hypotheses and suggest that contingency learning deficits might be important in the development and maintenance of the chronic pain-related disability. Chronic hand pain patients demonstrate 1) reduced differential contingency learning determined by a lack of safety belief formation, but not by exaggerated threat belief formation, and 2) flatter, asymmetric

Reduced tonic inhibition in the dentate gyrus contributes to chronic stress-induced impairments in learning and memory.

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Lee, Vallent; MacKenzie, Georgina; Hooper, Andrew; Maguire, Jamie

2016-10-01

It is well established that stress impacts the underlying processes of learning and memory. The effects of stress on memory are thought to involve, at least in part, effects on the hippocampus, which is particularly vulnerable to stress. Chronic stress induces hippocampal alterations, including but not limited to dendritic atrophy and decreased neurogenesis, which are thought to contribute to chronic stress-induced hippocampal dysfunction and deficits in learning and memory. Changes in synaptic transmission, including changes in GABAergic inhibition, have been documented following chronic stress. Recently, our laboratory demonstrated shifts in EGABA in CA1 pyramidal neurons following chronic stress, compromising GABAergic transmission and increasing excitability of these neurons. Interestingly, here we demonstrate that these alterations are unique to CA1 pyramidal neurons, since we do not observe shifts in EGABA following chronic stress in dentate gyrus granule cells. Following chronic stress, there is a decrease in the expression of the GABAA receptor (GABAA R) δ subunit and tonic GABAergic inhibition in dentate gyrus granule cells, whereas there is an increase in the phasic component of GABAergic inhibition, evident by an increase in the peak amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the numerous changes observed in the hippocampus following stress, it is difficult to pinpoint the pertinent contributing pathophysiological factors. Here we directly assess the impact of a reduction in tonic GABAergic inhibition of dentate gyrus granule cells on learning and memory using a mouse model with a decrease in GABAA R δ subunit expression specifically in dentate gyrus granule cells (Gabrd/Pomc mice). Reduced GABAA R δ subunit expression and function in dentate gyrus granule cells is sufficient to induce deficits in learning and memory. Collectively, these findings suggest that the reduction in GABAA R δ subunit-mediated tonic inhibition

Reduced tonic inhibition in the dentate gyrus contributes to chronic stress-induced impairments in learning and memory

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Hooper, Andrew; Maguire, Jamie

2016-01-01

It is well established that stress impacts the underlying processes of learning and memory. The effects of stress on memory are thought to involve, at least in part, effects on the hippocampus, which is particularly vulnerable to stress. Chronic stress induces hippocampal alterations, including but not limited to dendritic atrophy and decreased neurogenesis, which are thought to contribute to chronic stress-induced hippocampal dysfunction and deficits in learning and memory. Changes in synaptic transmission, including changes in GABAergic inhibition, have been documented following chronic stress. Recently, our laboratory demonstrated shifts in EGABA in CA1 pyramidal neurons following chronic stress, compromising GABAergic transmission and increasing excitability of these neurons. Interestingly, here we demonstrate that these alterations are unique to CA1 pyramidal neurons, since we do not observe shifts in EGABA following chronic stress in dentate gyrus granule cells. Following chronic stress, there is a decrease in the expression of the GABAA receptor (GABAAR) δ subunit and tonic GABAergic inhibition in dentate gyrus granule cells; whereas, there is an increase in the phasic component of GABAergic inhibition, evident by an increase in the peak amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the numerous changes observed in the hippocampus following stress, it is difficult to pinpoint the pertinent contributing pathophysiological factors. Here we directly assess the impact of a reduction in tonic GABAergic inhibition of dentate gyrus granule cells on learning and memory using a mouse model with a decrease in GABAAR δ subunit expression specifically in dentate gyrus granule cells (Gabrd/Pomc mice). Reduced GABAAR δ subunit expression and function in dentate gyrus granule cells is sufficient to induce deficits in learning and memory. Collectively, these findings suggest that the reduction in GABAAR δ subunit-mediated tonic inhibition in

The 50s cliff: a decline in perceptuo-motor learning, not a deficit in visual motion perception.

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Ren, Jie; Huang, Shaochen; Zhang, Jiancheng; Zhu, Qin; Wilson, Andrew D; Snapp-Childs, Winona; Bingham, Geoffrey P

2015-01-01

Previously, we measured perceptuo-motor learning rates across the lifespan and found a sudden drop in learning rates between ages 50 and 60, called the "50s cliff." The task was a unimanual visual rhythmic coordination task in which participants used a joystick to oscillate one dot in a display in coordination with another dot oscillated by a computer. Participants learned to produce a coordination with a 90° relative phase relation between the dots. Learning rates for participants over 60 were half those of younger participants. Given existing evidence for visual motion perception deficits in people over 60 and the role of visual motion perception in the coordination task, it remained unclear whether the 50s cliff reflected onset of this deficit or a genuine decline in perceptuo-motor learning. The current work addressed this question. Two groups of 12 participants in each of four age ranges (20s, 50s, 60s, 70s) learned to perform a bimanual coordination of 90° relative phase. One group trained with only haptic information and the other group with both haptic and visual information about relative phase. Both groups were tested in both information conditions at baseline and post-test. If the 50s cliff was caused by an age dependent deficit in visual motion perception, then older participants in the visual group should have exhibited less learning than those in the haptic group, which should not exhibit the 50s cliff, and older participants in both groups should have performed less well when tested with visual information. Neither of these expectations was confirmed by the results, so we concluded that the 50s cliff reflects a genuine decline in perceptuo-motor learning with aging, not the onset of a deficit in visual motion perception.

Unraveling the involvement of ABA in the water deficit-induced modulation of nitrogen metabolism in Medicago truncatula seedlings.

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Planchet, Elisabeth; Rannou, Olivier; Ricoult, Claudie; Limami, Anis M

2011-07-01

Effects of water deficit and/or abscisic acid (ABA) were investigated on early seedling growth of Medicago truncatula, and on glutamate metabolism under dark conditions. Water deficit (simulated by polyethylene glycol, PEG), ABA and their combination resulted in a reduction in growth rate of the embryo axis, and also in a synergistic increase of free amino acid (AA) content. However, the inhibition of water uptake retention induced by water deficit seemed to occur in an ABA-independent manner. Expression of several genes involved in glutamate metabolism was induced during water deficit, whereas ABA, in combination or not with PEG, repressed them. The only exception came from a gene encoding 1-pyrroline-5-carboxylate synthetase (P5CS) which appeared to be induced in an ABA-dependent manner under water deficit. Our results demonstrate clearly the involvement of an ABA-dependent and an ABA-independent regulatory system, governing growth and glutamate metabolism under water deficit.

A Meta-Analysis of Working Memory Deficits in Children with Learning Difficulties: Is There a Difference between Verbal Domain and Numerical Domain?

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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…

Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory.

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Heisler, Jillian M; O'Connor, Jason C

2015-11-01

Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. Published by Elsevier Inc.

Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory

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Heisler, Jillian M.; O’Connor, Jason C.

2015-01-01

Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. PMID:26130057

Sodium Phenylbutyrate and Edaravone Abrogate Chronic Restraint Stress-Induced Behavioral Deficits: Implication of Oxido-Nitrosative, Endoplasmic Reticulum Stress Cascade, and Neuroinflammation.

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Jangra, Ashok; Sriram, Chandra Shaker; Dwivedi, Shubham; Gurjar, Satendra Singh; Hussain, Md Iftikar; Borah, Probodh; Lahkar, Mangala

2017-01-01

Chronic stress exposure can produce deleterious effects on the hippocampus (HC) which eventually leads to cognitive impairment and depression. Endoplasmic reticulum (ER) stress has been reported as one of the major culprits in the development of stress-induced cognitive impairment and depression. We investigated the neuroprotective efficacy of sodium phenylbutyrate (SPB), an ER stress inhibitor, and edaravone, a free radical scavenger, against chronic restraint stress (CRS)-induced cognitive deficits and anxiety- and depressive-like behavior in mice. Adult male Swiss albino mice were restrained for 6 h/day for 28 days and injected (i.p.) with SPB (40 and 120 mg/kg) or edaravone (3 and 10 mg/kg) for the last seven days. After stress cessation, the anxiety- and depressive-like behavior along with spatial learning and memory were examined. Furthermore, oxido-nitrosative stress, proinflammatory cytokines, and gene expression level of ER stress-related genes were assessed in HC and prefrontal cortex (PFC). CRS-exposed mice showed anxiety- and depressive-like behavior, which was significantly improved by SPB and edaravone treatment. In addition, SPB and edaravone treatment significantly alleviated CRS-induced spatial learning and memory impairment. Furthermore, CRS-evoked oxido-nitrosative stress, neuroinflammation, and depletion of Brain-derived neurotrophic factor were significantly ameliorated by SPB and edaravone treatment. We found significant up-regulation of ER stress-related genes in both HC and PFC regions, which were suppressed by SPB and edaravone treatment in CRS mice. Our study provides evidence that SPB and edaravone exerted neuroprotective effects on CRS-induced cognitive deficits and anxiety- and depressive-like behavior, which is possibly coupled with inhibition of oxido-nitrosative stress, neuroinflammation, and ER stress cascade.

Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat

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Hanlon, Lauren A.; Huh, Jimmy W.

2016-01-01

Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID:26825312

Citalopram Ameliorates Synaptic Plasticity Deficits in Different Cognition-Associated Brain Regions Induced by Social Isolation in Middle-Aged Rats.

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Gong, Wei-Gang; Wang, Yan-Juan; Zhou, Hong; Li, Xiao-Li; Bai, Feng; Ren, Qing-Guo; Zhang, Zhi-Jun

2017-04-01

Our previous experiments demonstrated that social isolation (SI) caused AD-like tau hyperphosphorylation and spatial memory deficits in middle-aged rats. However, the underlying mechanisms of SI-induced spatial memory deficits remain elusive. Middle-aged rats (10 months) were group or isolation reared for 8 weeks. Following the initial 4-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Then, pathophysiological changes were assessed by performing behavioral, biochemical, and pathological analyses. We found that SI could cause cognitive dysfunction and decrease synaptic protein (synaptophysin or PSD93) expression in different brain regions associated with cognition, such as the prefrontal cortex, dorsal hippocampus, ventral hippocampus, amygdala, and caudal putamen, but not in the entorhinal cortex or posterior cingulate. Citalopram could significantly improve learning and memory and partially restore synaptophysin or PSD93 expression in the prefrontal cortex, hippocampus, and amygdala in SI rats. Moreover, SI decreased the number of dendritic spines in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus, which could be reversed by citalopram. Furthermore, SI reduced the levels of BDNF, serine-473-phosphorylated Akt (active form), and serine-9-phosphorylated GSK-3β (inactive form) with no significant changes in the levels of total GSK-3β and Akt in the dorsal hippocampus, but not in the posterior cingulate. Our results suggest that decreased synaptic plasticity in cognition-associated regions might contribute to SI-induced cognitive deficits, and citalopram could ameliorate these deficits by promoting synaptic plasticity mainly in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus. The BDNF/Akt/GSK-3β pathway plays an important role in regulating synaptic plasticity in SI rats.

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.

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

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Portero-Tresserra, Marta; Cristóbal-Narváez, Paula; Martí-Nicolovius, Margarita; Guillazo-Blanch, Gemma; Vale-Martínez, Anna

2013-01-01

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.

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

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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.

Jordan-3: measuring visual reversals in children as symptoms of learning disability and attention-deficit/hyperactivity disorder.

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Jordan, Brian T; Martin, Nancy; Austin, J Sue

2012-12-01

The purpose of this research was to establish new norms for the Jordan-3 for children ages 5 to 18 years. The research also investigated the frequency of visual reversals in children previously identified as having reading disability, attention-deficit/hyperactivity disorder, and broader learning disabilities. Participants were regular education students, ages 5 through 18 years, and special education students previously diagnosed with attention-deficit/hyperactivity disorder, reading disability, or broader learning disability. Jordan-3 Accuracy and Error raw scores were compared to assess if there was a significant difference between the two groups. Mean Accuracy and Error scores were compared for males and females. Children with learning disability and attention-deficit/hyperactivity disorder had higher reversals when compared to regular education children, which lends continued support to the Jordan-3 as a valid and reliable measure of visual reversals in children and adolescents. This study illustrates the utility of the Jordan-3 when assessing children who may require remediation to reach their academic potential.

Prenatal phencyclidine treatment induces behavioral deficits through impairment of GABAergic interneurons in the prefrontal cortex.

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Toriumi, Kazuya; Oki, Mika; Muto, Eriko; Tanaka, Junko; Mouri, Akihiro; Mamiya, Takayoshi; Kim, Hyoung-Chun; Nabeshima, Toshitaka

2016-06-01

We previously reported that prenatal treatment with phencyclidine (PCP) induces glutamatergic dysfunction in the prefrontal cortex (PFC), leading to schizophrenia-like behavioral deficits in adult mice. However, little is known about the prenatal effect of PCP treatment on other types of neurons. We focused on γ-aminobutyric acid (GABA)-ergic interneurons and evaluated the effect of prenatal PCP exposure on the neurodevelopment of GABAergic interneurons in the PFC. PCP was administered at the dose of 10 mg/kg/day to pregnant dams from embryonic day 6.5 to 18.5. After the pups were reared to adult, we analyzed their GABAergic system in the PFC using immunohistological, biochemical, and behavioral analyses in adulthood. The prenatal PCP treatment decreased the density of parvalbumin-positive cells and reduced the expression level of glutamic acid decarboxylase 67 (GAD67) and GABA content of the PFC in adults. Additionally, prenatal PCP treatment induced behavioral deficits in adult mice, such as hypersensitivity to PCP and prepulse inhibition (PPI) deficits. These behavioral deficits were ameliorated by pretreatment with the GABAB receptor agonist baclofen. Furthermore, the density of c-Fos-positive cells was decreased after the PPI test in the PFC of mice treated with PCP prenatally, and this effect was ameliorated by pretreatment with baclofen. These findings suggest that prenatal treatment with PCP induced GABAergic dysfunction in the PFC, which caused behavioral deficits.

Hyperactivity and memory/learning deficits evoked by developmental exposure to nicotine and/or ethanol are mitigated by cAMP and cGMP signaling cascades activation.

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Abreu-Villaça, Yael; Carvalho-Graça, Anna C; Skinner, Gabriela; Lotufo, Bruna M; Duarte-Pinheiro, Vitor H S; Ribeiro-Carvalho, Anderson; Manhães, Alex C; Filgueiras, Claudio C

2018-04-10

Pregnant smoking women are frequently episodic drinkers. Here, we investigated whether ethanol exposure restricted to the brain growth spurt period when combined with chronic developmental exposure to nicotine aggravates memory/learning deficits and hyperactivity, and associated cAMP and cGMP signaling disruption. To further investigate the role of these signaling cascades, we verified whether vinpocetine (a phosphodiesterase inhibitor) ameliorates the neurochemical and behavioral outcomes. Swiss mice had free access to nicotine (NIC, 50 μg/ml) or water to drink during gestation and until the 8th postnatal day (PN8). Ethanol (ETOH, 5 g/kg, i.p.) or saline were injected in the pups every other day from PN2 to PN8. At PN30, animals either received vinpocetine (20 mg/kg, i.p.) or vehicle before being tested in the step-down passive avoidance or open field. Memory/learning was impaired in NIC, ETOH and NIC + ETOH mice, and vinpocetine mitigated ETOH- and NIC + ETOH-induced deficits. Locomotor hyperactivity identified in ETOH and NIC + ETOH mice was ameliorated by vinpocetine. While cyclic nucleotides levels in cerebral cortex and hippocampus were reduced by NIC, ETOH and NIC + ETOH, this outcome was more consistent in the latter group. As observed for behavior, vinpocetine normalized NIC + ETOH nucleotides levels. pCREB levels were also increased in response to vinpocetine, with stronger effects in the NIC + ETOH group. Exposure to both drugs of abuse worsens behavioral and neurochemical disruption. These findings and the amelioration of deleterious effects by vinpocetine support the idea that cAMP and cGMP signaling contribute to nicotine- and ethanol-induced hyperactivity and memory/learning deficits. Copyright © 2018 Elsevier B.V. All rights reserved.

The effect of Vitamin E on learning and memory deficits in intrahippocampal kainate-induced temporal lobe epilepsy in rats.

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Kiasalari, Zahra; Khalili, Mohsen; Shafiee, Samaneh; Roghani, Mehrdad

2016-01-01

Since temporal lobe epilepsy (TLE) is associated with learning and memory impairment, we investigated the beneficial effect of Vitamin E on the impaired learning and memory in the intrahippocampal kainate model of TLE in rats. Rats were divided into sham, Vitamin E-treated sham, kainate, and Vitamin E-treated kainate. Intrahippocampal kainate was used for induction of epilepsy. Vitamin E was injected intraperitoneal (i.p.) at a dose of 200 mg/kg/day started 1 week before surgery until 1 h presurgery. Initial and step-through latencies in the passive avoidance test and alternation behavior percentage in Y-maze were finally determined in addition to measurement of some oxidative stress markers. Kainate injection caused a higher severity and rate of seizures and deteriorated learning and memory performance in passive avoidance paradigm and spontaneous alternation as an index of spatial recognition memory in Y-maze task. Intrahippocampal kainate also led to the elevation of malondialdehyde (MDA) and nitrite and reduced activity of superoxide dismutase (SOD). Vitamin E pretreatment significantly attenuated severity and incidence rate of seizures, significantly improved retrieval and recall in passive avoidance, did not ameliorate spatial memory deficit in Y-maze, and lowered MDA and enhanced SOD activity. Vitamin E improves passive avoidance learning and memory and part of its beneficial effect is due to its potential to mitigate hippocampal oxidative stress.

A specific implicit sequence learning deficit as an underlying cause of dyslexia? Investigating the role of attention in implicit learning tasks.

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Staels, Eva; Van den Broeck, Wim

2017-05-01

Recently, a general implicit sequence learning deficit was proposed as an underlying cause of dyslexia. This new hypothesis was investigated in the present study by including a number of methodological improvements, for example, the inclusion of appropriate control conditions. The second goal of the study was to explore the role of attentional functioning in implicit and explicit learning tasks. In a 2 × 2 within-subjects design 4 tasks were administered in 30 dyslexic and 38 control children: an implicit and explicit serial reaction time (RT) task and an implicit and explicit contextual cueing task. Attentional functioning was also administered. The entire learning curves of all tasks were analyzed using latent growth curve modeling in order to compare performances between groups and to examine the role of attentional functioning on the learning curves. The amount of implicit learning was similar for both groups. However, the dyslexic group showed slower RTs throughout the entire task. This group difference reduced and became nonsignificant after controlling for attentional functioning. Both implicit learning tasks, but none of the explicit learning tasks, were significantly affected by attentional functioning. Dyslexic children do not suffer from a specific implicit sequence learning deficit. The slower RTs of the dyslexic children throughout the entire implicit sequence learning process are caused by their comorbid attention problems and overall slowness. A key finding of the present study is that, in contrast to what was assumed for a long time, implicit learning relies on attentional resources, perhaps even more than explicit learning does. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism.

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Piochon, Claire; Kloth, Alexander D; Grasselli, Giorgio; Titley, Heather K; Nakayama, Hisako; Hashimoto, Kouichi; Wan, Vivian; Simmons, Dana H; Eissa, Tahra; Nakatani, Jin; Cherskov, Adriana; Miyazaki, Taisuke; Watanabe, Masahiko; Takumi, Toru; Kano, Masanobu; Wang, Samuel S-H; Hansel, Christian

2014-11-24

A common feature of autism spectrum disorder (ASD) is the impairment of motor control and learning, occurring in a majority of children with autism, consistent with perturbation in cerebellar function. Here we report alterations in motor behaviour and cerebellar synaptic plasticity in a mouse model (patDp/+) for the human 15q11-13 duplication, one of the most frequently observed genetic aberrations in autism. These mice show ASD-resembling social behaviour deficits. We find that in patDp/+ mice delay eyeblink conditioning--a form of cerebellum-dependent motor learning--is impaired, and observe deregulation of a putative cellular mechanism for motor learning, long-term depression (LTD) at parallel fibre-Purkinje cell synapses. Moreover, developmental elimination of surplus climbing fibres--a model for activity-dependent synaptic pruning--is impaired. These findings point to deficits in synaptic plasticity and pruning as potential causes for motor problems and abnormal circuit development in autism.

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

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Uta Waterhouse

2016-10-01

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

Mazindol attenuates ketamine-induced cognitive deficit in the attentional set shifting task in rats.

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Nikiforuk, Agnieszka; Gołembiowska, Krystyna; Popik, Piotr

2010-01-01

Cognitive impairments associated with schizophrenia await an effective treatment. In order to model schizophrenia-like cognitive deficits in rats, we evaluated the effects of ketamine, a dissociative anesthetic NMDA/glutamate receptor channel blocker in the attentional set-shifting task (ASST). Acute administration of ketamine (10 but not 3mg/kg) selectively impaired solving of the extradimensional (ED) set-shifting component. Next, we investigated whether the co-administration of mazindol, a dopamine and norepinephrine reuptake inhibitor would protect rats from ketamine-induced deficits. Mazindol dose-dependently and selectively alleviated ketamine-induced ED deficit with a minimal effective dose of 0.5mg/kg. The ED component improvement was noted primarily in ketamine - but not in vehicle co-treated rats, in which the drug facilitated ED shift solving at the dose as high as 5mg/kg. A "positive control", sertindole (2.5mg/kg) also ameliorated ketamine-induced ED deficit. Microdialysis of the prefrontal cortex in a separate group of animals revealed that 2-3h after the administration of 5mg/kg of mazindol and ketamine (i.e., at the time of ED component solving), the extracellular concentrations of dopamine were enhanced by ~300% as compared to the baseline and were intermediate between the mazindol- and ketamine-treated reference groups. However, at that time the levels of norepinephrine, serotonin and glutamate appeared unaffected. We conclude that ketamine may be useful in mimicking deficits specifically related to cognitive inflexibility observed in schizophrenia, and suggest that these anomalies could be ameliorated by mazindol. The beneficial effects of mazindol on ASST performance may have therapeutic implications for the treatment of schizophrenia.

Deficits in learning and memory in mice with a mutation of the candidate dyslexia susceptibility gene Dyx1c1.

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Rendall, Amanda R; Tarkar, Aarti; Contreras-Mora, Hector M; LoTurco, Joseph J; Fitch, R Holly

2017-09-01

Dyslexia is a learning disability characterized by difficulty learning to read and write. The underlying biological and genetic etiology remains poorly understood. One candidate gene, dyslexia susceptibility 1 candidate 1 (DYX1C1), has been shown to be associated with deficits in short-term memory in dyslexic populations. The purpose of the current study was to examine the behavioral phenotype of a mouse model with a homozygous conditional (forebrain) knockout of the rodent homolog Dyx1c1. Twelve Dyx1c1 conditional homozygous knockouts, 7 Dyx1c1 conditional heterozygous knockouts and 6 wild-type controls were behaviorally assessed. Mice with the homozygous Dyx1c1 knockout showed deficits on memory and learning, but not on auditory or motor tasks. These findings affirm existing evidence that DYX1C1 may play an underlying role in the development of neural systems important to learning and memory, and disruption of this function could contribute to the learning deficits seen in individuals with dyslexia. Copyright © 2015 Elsevier Inc. All rights reserved.

Performance deficits following failure: learned helplessness or self-esteem protection?

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Witkowski, T; Stiensmeier-Pelster, J

1998-03-01

We report two laboratory experiments which compare two competing explanations of performance deficits following failure: one based on Seligman's learned helplessness theory (LHT), and the other, on self-esteem protection theory (SEPT). In both studies, participants (Study 1: N = 40 pupils from secondary schools in Walbrzych, Poland; Study 2: N = 45 students from the University of Bielefeld, Germany) were confronted with either success or failure in a first phase of the experiment. Then, in the second phase of the experiment the participants had to work on a set of mathematical problems (Study 1) or a set of tasks taken from Raven's Progressive Matrices (Study 2) either privately or in public. In both studies failure in the first phase causes performance deficits in the second phase only if the participants had to solve the test tasks in public. These results were interpreted in line with SEPT and as incompatible with LHT.

Intermittent hypoxia-induced cognitive deficits are mediated by NADPH oxidase activity in a murine model of sleep apnea.

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Deepti Nair

Full Text Available In rodents, exposure to intermittent hypoxia (IH, a hallmark of obstructive sleep apnea (OSA, is associated with neurobehavioral impairments, increased apoptosis in the hippocampus and cortex, as well as increased oxidant stress and inflammation. Excessive NADPH oxidase activity may play a role in IH-induced CNS dysfunction.The effect of IH during light period on two forms of spatial learning in the water maze and well as markers of oxidative stress was assessed in mice lacking NADPH oxidase activity (gp91phox(_/Y and wild-type littermates. On a standard place training task, gp91phox(_/Y displayed normal learning, and were protected from the spatial learning deficits observed in wild-type littermates exposed to IH. Moreover, anxiety levels were increased in wild-type mice exposed to IH as compared to room air (RA controls, while no changes emerged in gp91phox(_/Y mice. Additionally, wild-type mice, but not gp91phox(_/Y mice had significantly elevated levels of NADPH oxidase expression and activity, as well as MDA and 8-OHDG in cortical and hippocampal lysates following IH exposures.The oxidative stress responses and neurobehavioral impairments induced by IH during sleep are mediated, at least in part, by excessive NADPH oxidase activity, and thus pharmacological agents targeting NADPH oxidase may provide a therapeutic strategy in sleep-disordered breathing.

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

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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.

Abnormal-induced theta activity supports early directed-attention network deficits in progressive MCI.

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Deiber, Marie-Pierre; Ibañez, Vicente; Missonnier, Pascal; Herrmann, François; Fazio-Costa, Lara; Gold, Gabriel; Giannakopoulos, Panteleimon

2009-09-01

The electroencephalography (EEG) theta frequency band reacts to memory and selective attention paradigms. Global theta oscillatory activity includes a posterior phase-locked component related to stimulus processing and a frontal-induced component modulated by directed attention. To investigate the presence of early deficits in the directed attention-related network in elderly individuals with mild cognitive impairment (MCI), time-frequency analysis at baseline was used to assess global and induced theta oscillatory activity (4-6Hz) during n-back working memory tasks in 29 individuals with MCI and 24 elderly controls (EC). At 1-year follow-up, 13 MCI patients were still stable and 16 had progressed. Baseline task performance was similar in stable and progressive MCI cases. Induced theta activity at baseline was significantly reduced in progressive MCI as compared to EC and stable MCI in all n-back tasks, which were similar in terms of directed attention requirements. While performance is maintained, the decrease of induced theta activity suggests early deficits in the directed-attention network in progressive MCI, whereas this network is functionally preserved in stable MCI.

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

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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…

Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice

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Kesby, James P.; Markou, Athina; Semenova, Svetlana

2014-01-01

Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e., similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. PMID:25476577

Neuropsychological evaluation of deficits in executive functioning for ADHD children with or without learning disabilities.

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Wu, Kitty K; Anderson, Vicki; Castiello, Umberto

2002-01-01

This study investigates multiple aspects of executive functioning in children with attention deficit/hyperactivity disorder (ADHD). These areas include attentional components, impulsiveness, planning, and problem solving. The rationale of the study is based on neurophysiological studies that suggest frontal lobe dysfunction in ADHD. As frontal lobe functioning is related to abilities in executive control, ADHD is hypothesised to be associated with deficits in various areas of executive functioning. The specific effect of comorbidity of learning disability (LD) was also investigated. Eighty-three children with ADHD and 29 age-matched controls (age 7-13) participated in the study. A battery of neuropsychological tests was utilized to evaluate specific deficits in speed of processing, selective attention, switching attention, sustained attention, attentional capacity, impulsiveness, planning and problem solving. Findings indicated that children with ADHD have slower verbal responses and sustained attention deficit. Deficits in selective attention and attentional capacity observed were largely related to the presence of LD. No specific deficit associated with ADHD or the comorbidity of LD was identified in switching attention, impulsiveness, planning, and problem solving. These results revealed that ADHD is not associated with a general deficit in executive functioning. Instead, ADHD is related to a specific deficit in regulation for attentional resources. The importance of isolating the deficit related to LDs for examining the specific deficit associated with ADHD is highlighted. Results also emphasised the importance of isolating the effect of lower level of abilities (e.g., speed of processing) and the utilization of specific definition for the examination of executive functions.

Neuroscience illuminating the influence of auditory or phonological intervention on language-related deficits

Directory of Open Access Journals (Sweden)

Sari eYlinen

2015-02-01

Full Text Available Remediation programs for language-related learning deficits are urgently needed to enable equal opportunities in education. To meet this need, different training and intervention programs have been developed. Here we review, from an educational perspective, studies that have explored the neural basis of behavioral changes induced by auditory or phonological training in dyslexia, specific language impairment (SLI, and language-learning impairment (LLI. Training has been shown to induce plastic changes in deficient neural networks. In dyslexia, these include, most consistently, increased or normalized activation of previously hypoactive inferior frontal and occipito-temporal areas. In SLI and LLI, studies have shown the strengthening of previously weak auditory brain responses as a result of training. The combination of behavioral and brain measures of remedial gains has potential to increase the understanding of the causes of language-related deficits, which may help to target remedial interventions more accurately to the core problem.

Neurocognitive deficits as a barrier to psychosocial function in schizophrenia: effects on learning, coping, & self-concept.

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Lysaker, Paul H; Buck, Kelly D

2007-07-01

Recently, research has linked deficits in neurocognition, which emerge early in schizophrenia, with psychosocial impairments. However, it is uncertain how these deficits lead to sustained dysfunction. In this review, we explore how neurocognitive deficits could disrupt function at three levels: learning, coping preference, and self-concept. We offer a model in which neurocognitive impairment may directly limit skills acquisition and the development of a rich personal narrative. We suggest that both limited skills acquisition and an impoverished narrative may subsequently feed into a habitual style of avoidant coping, leading to a cycle of sustained dysfunction. Implications for cognitive, rehabilitation, and psychotherapeutic interventions are discussed.

Academic Risk Factors and Deficits of Learned Hopelessness: A Longitudinal Study of Hong Kong Secondary School Students

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Au, Raymond C. P.; Watkins, David A.; Hattie, John A. C.

2010-01-01

The aim of the present study is to explore a causal model of academic achievement and learning-related personal variables by testing the nature of relationships between learned hopelessness, its risk factors and hopelessness deficits as proposed in major theories in this area. The model investigates affective-motivational characteristics of…

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

Learning Styles of Students with Attention Deficit Hyperactivity Disorder: Who Are They and How Can We Teach Them?

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Brand, Susan; Dunn, Rita; Greb, Fran

2002-01-01

Proposes that students with Attention Deficit Hyperactivity Disorder (ADHD) learn differently than other students. Discusses two studies of ADHD students. Concludes such students may learn better in the afternoon instead of the morning; with tactile and kinesthetic instructional resources; in soft illumination; with Multisensory Instructional…

Rats with congenital learned helplessness respond less to sucrose but show no deficits in activity or learning.

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Vollmayr, Barbara; Bachteler, Daniel; Vengeliene, Valentina; Gass, Peter; Spanagel, Rainer; Henn, Fritz

2004-04-02

Inbred rat strains for congenital learned helplessness (cLH) and for congenital resistance to learned helplessness (cNLH) were investigated as a model to study genetic predisposition to major depression. Congenitally helpless rats respond less to sucrose under a progressive ratio schedule. This is not confounded by locomotor hypoactivity: in contrast, cLH rats show a slight hyperactivity during the first 5 min of an open field test. cLH rats acquire operant responding to sucrose as readily as cNLH rats and exhibit normal memory acquisition and retrieval in the Morris water maze, thus ruling out general learning deficits as the cause of the decreased response to sucrose. Reduced total responses and reduced breaking points for sucrose in the cLH strain argue for anhedonia, which is an analogue to loss of pleasure essential for the diagnosis of major depressive episodes, and thus confirm the validity of congenitally learned helpless rats as a model of major depression.

Piperine Augments the Protective Effect of Curcumin Against Lipopolysaccharide-Induced Neurobehavioral and Neurochemical Deficits in Mice.

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Jangra, Ashok; Kwatra, Mohit; Singh, Tavleen; Pant, Rajat; Kushwah, Pawan; Sharma, Yogita; Saroha, Babita; Datusalia, Ashok Kumar; Bezbaruah, Babul Kumar

2016-06-01

The aim of the present study was to investigate the protective effects of curcumin alone and in combination with piperine against lipopolysaccharide (LPS)-induced neurobehavioral and neurochemical deficits in the mice hippocampus. Mice were treated with curcumin (100, 200, and 400 mg/kg, p.o.) and piperine (20 mg/kg, p.o.) for 7 days followed by LPS (0.83 mg/kg, i.p.) administration. Animals exhibited anxiety and depressive-like phenotype after 3 and 24 h of LPS exposure, respectively. LPS administration increased the oxido-nitrosative stress as evident by elevated levels of malondialdehyde, nitrite, and depletion of glutathione level in the hippocampus. Furthermore, we found raised level of pro-inflammatory cytokines (IL-1β and TNF-α) in the hippocampus of LPS-treated mice. Pretreatment with curcumin alleviated LPS-induced neurobehavioral and neurochemical deficits. Furthermore, co-administration of curcumin with piperine significantly potentiated the neuroprotective effect of curcumin. These results demonstrate that piperine enhanced the neuroprotective effect of curcumin against LPS-induced neurobehavioral and neurochemical deficits.

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

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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.

Simvastatin Attenuates Neurogenetic Damage and Improves Neurocongnitive Deficits Induced by Isoflurane in Neonatal Rats

Directory of Open Access Journals (Sweden)

Ning Wang

2018-03-01

Full Text Available Background/Aims: Isoflurane inhibited neurogenesis and induced subsequent neurocognitive deficits in developing brain. Simvastatin exerts neuroprotection in a wide range of brain injury models. In the present study, we investigated whether simvastatin could attenuate neurogenetic inhibition and cognitive deficits induced by isoflurane exposure in neonatal rats. Methods: Sprague-Dawley rats at postnatal day (PND 7 and neural stem cells (NSCs were treated with either gas mixture, isoflurane, or simvastatin 60 min prior to isoflurane exposure, respectively. The rats were decapitated at PND 8 and PND 10 for detection of neurogenesis in the subventricular zone (SVZ and subgranular zone (SGZ of the hippocampus by immunostaining. NSC proliferation, viability and apoptosis were assessed by immunohistochemistry, CCK-8 and TUNEL, respectively. The protein expressions of caspase-3, p-Akt and p-GSK-3β both in vivo and vitro were assessed by western blotting. Cognitive functions were assessed by Morris Water Maze test and context fear conditioning test at the adult. Results: Isoflurane exposure inhibited neurogenesis in the SVZ and SGZ, decreased NSC proliferation and viability, promoted NSC apoptosis and led to late cognitive deficits. Furthermore, isoflurane increased caspase-3 expression and decreased protein expressions of p-Akt and p-GSK-3β both in vivo and in vitro. Pretreatment with simvastatin attenuated isoflurane-elicited changes in NSCs and cognitive function. Co-treatment with LY294002 reversed the effect of simvastatin on NSCs in vitro. Conclusion: We for the first time showed that simvastatin, by upregulating Akt/GSK-3β signaling pathway, alleviated isoflurane-induced neurogenetic damage and neurocognitive deficits in developing rat brain.

ADHD and retrieval-induced forgetting: evidence for a deficit in the inhibitory control of memory.

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Storm, Benjamin C; White, Holly A

2010-04-01

Research on retrieval-induced forgetting has shown that the selective retrieval of some information can cause the forgetting of other information. Such forgetting is believed to result from inhibitory processes that function to resolve interference during retrieval. The current study examined whether individuals with ADHD demonstrate normal levels of retrieval-induced forgetting. A total of 40 adults with ADHD and 40 adults without ADHD participated in a standard retrieval-induced forgetting experiment. Critically, half of the items were tested using category cues and the other half of the items were tested using category-plus-one-letter-stem cues. Whereas both ADHD and non-ADHD participants demonstrated retrieval-induced forgetting on the final category-cued recall test, only non-ADHD participants demonstrated retrieval-induced forgetting on the final category-plus-stem-cued recall test. These results suggest that individuals with ADHD do have a deficit in the inhibitory control of memory, but that this deficit may only be apparent when output interference is adequately controlled on the final test.

Learning induces the translin/trax RNase complex to express activin receptors for persistent memory.

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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.

Histamine ameliorates spatial memory deficits induced by MK-801 infusion into ventral hippocampus as evaluated by radial maze task in rats

Institute of Scientific and Technical Information of China (English)

Li-sha XU; Li-xia YANG; Wei-wei HU; Xiao YU; Li MA; Lu-ying LIU; Er-qing WEI; Zhong CHEN

2005-01-01

Aim: To investigate the role of histamine in memory deficits induced by MK-801 infusion into the ventral hippocampus in rats. Methods: An 8-arm radial maze (4arms baited) was used to assess spatial memory. Results: Bilateral ventral intrahippocampal (ih) infusion of MK-801 (0.3 μg/site), an N-methyl-D-aspartate (NMDA) antagonist, impaired the retrieval process in both working memory and reference memory. Intrahippocampal injection of histamine (25 or 50 ng/site) or intraperitoneal (ip) injection of histidine (25, 50 or 100 mg/kg) markedly ameliorated the spatial memory deficits induced by MK-801. Both the histamine H1 antagonist pyrilamine (0.5 or 1.0 μg/site, ih) and the H2 antagonist cimetidine (2.5 μg/site,ih) abolished the ameliorating effect of histidine (100 mg/kg, ip) on reference memory deficits, but not that on working memory deficits induced by MK-801. Conclusion:The results indicate that histamine in the ventral hippocampus can ameliorate MK-801-induced spatial memory deficits, and that histamine's effect on reference memory is mediated by postsynaptic histamine H1 and H2 receptors.

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

Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents

DEFF Research Database (Denmark)

Bubser, Michael; Bridges, Thomas M; Dencker, Ditte

2014-01-01

PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801....... VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant...

Self-esteem in children with attention and/or learning deficits: the importance of gender.

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Ek, Ulla; Westerlund, Joakim; Holmberg, Kirsten; Fernell, Elisabeth

2008-08-01

Our objective was to analyze self-esteem in children within a spectrum of attention disorders, that is, besides attention deficit hyperactivity disorder (ADHD), also children with subthreshold ADHD and even milder attention deficits and/or learning problems. From a population-based group of 10-11-year-old children in a Swedish municipality those with ADHD/subthreshold ADHD (n = 30) and those with milder attention and/or learning problems (n = 64) were targeted for the study. The children completed the 'I think I am' scale, reflecting physical appearance, scholastic competence, mental well-being, relationships to parents and to others and global self-esteem. Data from boys and girls were compared and related to the parents' and teachers' ratings on the two dimensions of the Conners' 10-item questionnaire (impulsive-restless behaviour and emotional lability) and to the children's cognitive levels. Significant gender differences were found, girls reporting lower self-esteem concerning mental well-being and poorer relationships with parents and peers. However, children with ADHD/subthreshold ADHD did not report significantly lower global self-esteem when compared to a reference population. Self-esteem in children with attention, behaviour and/or learning problems has to be carefully evaluated, especially in girls, and measures are needed to prevent a trajectory towards adolescent psychopathology.

Edaravone alleviates cisplatin-induced neurobehavioral deficits via modulation of oxidative stress and inflammatory mediators in the rat hippocampus.

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Jangra, Ashok; Kwatra, Mohit; Singh, Tavleen; Pant, Rajat; Kushwah, Pawan; Ahmed, Sahabuddin; Dwivedi, Durgesh; Saroha, Babita; Lahkar, Mangala

2016-11-15

Cisplatin is a chemotherapeutic agent used in the treatment of malignant tumors. A major clinical limitation of cisplatin is its potential toxic effects, including neurotoxicity. Edaravone, a potent free radical scavenger, has been reported to have the neuroprotective effect against neurological deficits. The aim of the present study was to determine the neuroprotective effect of edaravone against cisplatin-induced behavioral and biochemical anomalies in male Wistar rats. Our results showed that cisplatin (5mg/kg/week, i.p.) administration for seven weeks caused marked cognitive deficits and motor incoordination in rats. This was accompanied by oxido-nitrosative stress, neuroinflammation, NF-κB activation and down-regulation of Nrf2/HO-1 gene expression level in the hippocampus. Edaravone (10mg/kg/week, i.p.) treatment for seven weeks inhibited the aforementioned neurobehavioral and neurochemical deficits. Furthermore, edaravone was found to up-regulate the gene expression level of Nrf2/HO-1 and prevented the cisplatin-induced NF-κB activation. These findings demonstrated that oxido-nitrosative stress and inflammatory signaling mediators play a key role in the development of cisplatin-induced neurobehavioral deficits which were prevented by edaravone treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Jobelyn® attenuates inflammatory responses and neurobehavioural deficits associated with complete Freund-adjuvant-induced arthritis in mice.

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Omorogbe, Osarume; Ajayi, Abayomi M; Ben-Azu, Benneth; Oghwere, Ejiroghene E; Adebesin, Adaeze; Aderibigbe, Adegbuyi O; Okubena, Olajuwon; Umukoro, Solomon

2018-02-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the physical and psychosocial wellbeing of the patients and a major cause of work disability. Current drugs for its treatment only provide palliative effect, as cure for the disease still remains elusive. Jobelyn ® (JB), a potent anti-oxidant and anti-inflammatory dietary supplement obtained from Sorghum bicolor, has been claimed to relieve arthritic pain. Thus, this study was designed to evaluate its effect on inflammatory and biochemical changes as well as neurobehavioural deficits associated with complete Freund-adjuvant (CFA)-induced arthritis in mice. The effect of JB (50, 100 and 200 mg/kg) on inflammatory oedema, neurobehavioural deficits, levels of biomarkers of oxidative stress and inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) induced by 0.1 mL of CFA (10 mg/mL) was evaluated in male Swiss mice. Oral administration of JB (100 and 200 mg/kg) reduced inflammatory paw volume and reversed sensorimotor deficits induced by CFA. JB also reduced pain episodes, anxiety and depressive-like symptoms in CFA-mice. The increased level of oxidative stress in the joint and brain tissues of CFA-mice was reduced by JB. It also decreased tumor necrosis factor-alpha and interleukin-6 levels induced by CFA in the joint tissue of mice. These findings suggest that Jobelyn ® attenuates inflammatory responses induced by CFA in mice via inhibition of oxidative stress and release of inflammatory cytokines. The ability of JB to attenuate CFA-induced nociception, sensorimotor deficits and depressive-like symptom suggests it might improve the quality of life of patients with arthritic conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A perceptual learning deficit in Chinese developmental dyslexia as revealed by visual texture discrimination training.

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Wang, Zhengke; Cheng-Lai, Alice; Song, Yan; Cutting, Laurie; Jiang, Yuzheng; Lin, Ou; Meng, Xiangzhi; Zhou, Xiaolin

2014-08-01

Learning to read involves discriminating between different written forms and establishing connections with phonology and semantics. This process may be partially built upon visual perceptual learning, during which the ability to process the attributes of visual stimuli progressively improves with practice. The present study investigated to what extent Chinese children with developmental dyslexia have deficits in perceptual learning by using a texture discrimination task, in which participants were asked to discriminate the orientation of target bars. Experiment l demonstrated that, when all of the participants started with the same initial stimulus-to-mask onset asynchrony (SOA) at 300 ms, the threshold SOA, adjusted according to response accuracy for reaching 80% accuracy, did not show a decrement over 5 days of training for children with dyslexia, whereas this threshold SOA steadily decreased over the training for the control group. Experiment 2 used an adaptive procedure to determine the threshold SOA for each participant during training. Results showed that both the group of dyslexia and the control group attained perceptual learning over the sessions in 5 days, although the threshold SOAs were significantly higher for the group of dyslexia than for the control group; moreover, over individual participants, the threshold SOA negatively correlated with their performance in Chinese character recognition. These findings suggest that deficits in visual perceptual processing and learning might, in part, underpin difficulty in reading Chinese. Copyright © 2014 John Wiley & Sons, Ltd.

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

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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.

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

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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.

Vagus nerve stimulation ameliorated deficits in one-way active avoidance learning and stimulated hippocampal neurogenesis in bulbectomized rats.

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Gebhardt, Nils; Bär, Karl-Jürgen; Boettger, Michael K; Grecksch, Gisela; Keilhoff, Gerburg; Reichart, Rupert; Becker, Axel

2013-01-01

Vagus nerve stimulation (VNS) has been introduced as a therapeutic option for treatment-resistant depression. The neural and chemical mechanisms responsible for the effects of VNS are largely unclear. Bilateral removal of the olfactory bulbs (OBX) is a validated animal model in depression research. We studied the effects of vagus nerve stimulation (VNS) on disturbed one-way active avoidance learning and neurogenesis in the hippocampal dentate gyrus of rats. After a stimulation period of 3 weeks, OBX rats acquired the learning task as controls. In addition, the OBX-related decrease of neuronal differentiated BrdU positive cells in the dentate gyrus was prevented by VNS. This suggests that chronic VNS and changes in hippocampal neurogenesis induced by VNS may also account for the amelioration of behavioral deficits in OBX rats. To the best of our knowledge, this is the first report on the restorative effects of VNS on behavioral function in an animal model of depression that can be compared with the effects of antidepressants. Copyright © 2013 Elsevier Inc. All rights reserved.

Water deficit stress-induced changes in carbon and nitrogen partitioning in Chenopodium quinoa Willd.

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Bascuñán-Godoy, Luisa; Reguera, Maria; Abdel-Tawab, Yasser M; Blumwald, Eduardo

2016-03-01

Water deficit stress followed by re-watering during grain filling resulted in the induction of the ornithine pathway and in changes in Quinoa grain quality. The genetic diversity of Chenopodium quinoa Willd. (Quinoa) is accompanied by an outstanding environmental adaptability and high nutritional properties of the grains. However, little is known about the biochemical and physiological mechanisms associated with the abiotic stress tolerance of Quinoa. Here, we characterized carbon and nitrogen metabolic changes in Quinoa leaves and grains in response to water deficit stress analyzing their impact on the grain quality of two lowland ecotypes (Faro and BO78). Differences in the stress recovery response were found between genotypes including changes in the activity of nitrogen assimilation-associated enzymes that resulted in differences in grain quality. Both genotypes showed a common strategy to overcome water stress including the stress-induced synthesis of reactive oxygen species scavengers and osmolytes. Particularly, water deficit stress induced the stimulation of the ornithine and raffinose pathways. Our results would suggest that the regulation of C- and N partitioning in Quinoa during grain filling could be used for the improvement of the grain quality without altering grain yields.

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.

Cerebellar Plasticity and Motor Learning Deficits in a Copy Number Variation Mouse Model of Autism

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Piochon, Claire; Kloth, Alexander D; Grasselli, Giorgio; Titley, Heather K; Nakayama, Hisako; Hashimoto, Kouichi; Wan, Vivian; Simmons, Dana H; Eissa, Tahra; Nakatani, Jin; Cherskov, Adriana; Miyazaki, Taisuke; Watanabe, Masahiko; Takumi, Toru; Kano, Masanobu; Wang, Samuel S-H; Hansel, Christian

2014-01-01

A common feature of autism spectrum disorder (ASD) is the impairment of motor control and learning, occurring in a majority of children with autism, consistent with perturbation in cerebellar function. Here we report alterations in motor behavior and cerebellar synaptic plasticity in a mouse model (patDp/+) for the human 15q11-13 duplication, one of the most frequently observed genetic aberrations in autism. These mice show ASD-resembling social behavior deficits. We find that in patDp/+ mice delay eyeblink conditioning—a form of cerebellum-dependent motor learning—is impaired, and observe deregulation of a putative cellular mechanism for motor learning, long-term depression (LTD) at parallel fiber-Purkinje cell synapses. Moreover, developmental elimination of surplus climbing fibers—a model for activity-dependent synaptic pruning—is impaired. These findings point to deficits in synaptic plasticity and pruning as potential causes for motor problems and abnormal circuit development in autism. PMID:25418414

A Critical Review of Self-Regulated Learning Interventions for Children with Attention-Deficit Hyperactivity Disorder

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Reddy, Linda A.; Cleary, Timothy J.; Alperin, Alexander; Verdesco, Arielle

2018-01-01

School practitioners and educators are frequently challenged by the diverse and pervasive academic and behavioral needs of children at risk for and with attention-deficit hyperactivity disorder (ADHD). This paper examines the outcome literature on self-regulated learning (SRL) interventions for youth with ADHD by systematically reviewing the key…

Role of state-dependent learning in the cognitive effects of caffeine in mice.

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Sanday, Leandro; Zanin, Karina A; Patti, Camilla L; Fernandes-Santos, Luciano; Oliveira, Larissa C; Longo, Beatriz M; Andersen, Monica L; Tufik, Sergio; Frussa-Filho, Roberto

2013-08-01

Caffeine is the most widely used psychoactive substance in the world and it is generally believed that it promotes beneficial effects on cognitive performance. However, there is also evidence suggesting that caffeine has inhibitory effects on learning and memory. Considering that caffeine may have anxiogenic effects, thus changing the emotional state of the subjects, state-dependent learning may play a role in caffeine-induced cognitive alterations. Mice were administered 20 mg/kg caffeine before training and/or before testing both in the plus-maze discriminative avoidance task (an animal model that concomitantly evaluates learning, memory, anxiety-like behaviour and general activity) and in the inhibitory avoidance task, a classic paradigm for evaluating memory in rodents. Pre-training caffeine administration did not modify learning, but produced an anxiogenic effect and impaired memory retention. While pre-test administration of caffeine did not modify retrieval on its own, the pre-test administration counteracted the memory deficit induced by the pre-training caffeine injection in both the plus-maze discriminative and inhibitory avoidance tasks. Our data demonstrate that caffeine-induced memory deficits are critically related to state-dependent learning, reinforcing the importance of considering the participation of state-dependency on the interpretation of the cognitive effects of caffeine. The possible participation of caffeine-induced anxiety alterations in state-dependent memory deficits is discussed.

Rats bred for helplessness exhibit positive reinforcement learning deficits which are not alleviated by an antidepressant dose of the MAO-B inhibitor deprenyl.

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Schulz, Daniela; Henn, Fritz A; Petri, David; Huston, Joseph P

2016-08-04

Principles of negative reinforcement learning may play a critical role in the etiology and treatment of depression. We examined the integrity of positive reinforcement learning in congenitally helpless (cH) rats, an animal model of depression, using a random ratio schedule and a devaluation-extinction procedure. Furthermore, we tested whether an antidepressant dose of the monoamine oxidase (MAO)-B inhibitor deprenyl would reverse any deficits in positive reinforcement learning. We found that cH rats (n=9) were impaired in the acquisition of even simple operant contingencies, such as a fixed interval (FI) 20 schedule. cH rats exhibited no apparent deficits in appetite or reward sensitivity. They reacted to the devaluation of food in a manner consistent with a dose-response relationship. Reinforcer motivation as assessed by lever pressing across sessions with progressively decreasing reward probabilities was highest in congenitally non-helpless (cNH, n=10) rats as long as the reward probabilities remained relatively high. cNH compared to wild-type (n=10) rats were also more resistant to extinction across sessions. Compared to saline (n=5), deprenyl (n=5) reduced the duration of immobility of cH rats in the forced swimming test, indicative of antidepressant effects, but did not restore any deficits in the acquisition of a FI 20 schedule. We conclude that positive reinforcement learning was impaired in rats bred for helplessness, possibly due to motivational impairments but not deficits in reward sensitivity, and that deprenyl exerted antidepressant effects but did not reverse the deficits in positive reinforcement learning. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Cognitive Training and Work Therapy for the Treatment of Verbal Learning and Memory Deficits in Veterans With Alcohol Use Disorders.

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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).

Improvement of Word Problem Solving and Basic Mathematics Competencies in Students with Attention Deficit/Hyperactivity Disorder and Mathematical Learning Difficulties

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González-Castro, Paloma; Cueli, Marisol; Areces, Débora; Rodríguez, Celestino; Sideridis, Georgios

2016-01-01

Problem solving represents a salient deficit in students with mathematical learning difficulties (MLD) primarily caused by difficulties with informal and formal mathematical competencies. This study proposes a computerized intervention tool, the integrated dynamic representation (IDR), for enhancing the early learning of basic mathematical…

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

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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.

Evaluating the Protective Effects of Melissa Officinalis on Learning Deficits of Rat’s Offspring Exposed to Lead Acetate During Pre- and Postnatal Periods

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Z Momeni

2010-01-01

Full Text Available Introduction & Objective: Lead contamination dramatically influences different body systems especially the central nervous system. Lead absorption during gestational period has deleterious effects on fetal differentiation and development and it may possibly result in learning deficits in adulthood. Recent studies have demonstrated positive effects of Melissa officinalis on memory improvement in some neural disorders. The aim of the present study is to investigate the protective effects of Melissa on learning deficits in lead acetate exposed rats. Materials & Methods: In this experimental study in department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad (2008-2009, 40 mated Wistar rats were divided into 8 groups as follows: control, negative control (Pb, Melissa (M and Pb+M, and each in 3 different subgroups. The treatment started from the 7th day of gestation and continued during pregnancy and lactation. The learning ability and memory retention of four months old offspring were tested by complex T-maze. The collected data was analyzed by the SPSS software using one-way ANOVA and Toki test. Results: A significant difference was found between lead exposed group and other groups regarding the time to reach the goal and the number of errors while there was no meaningful difference between the control and other experimental groups. Conclusion: In lead exposed rats, learning deficits were obviously noticed. Since there was meaningful difference between control and Pb+M subgroups, Melissa can possibly improve learning deficits in lead acetate exposed rats.

Mitigation of postnatal ethanol-induced neuroinflammation ameliorates trace fear memory deficits in juvenile rats.

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Goodfellow, Molly J; Shin, Youn Ju; Lindquist, Derick H

2018-02-15

Impairments in behavior and cognition are common in individuals diagnosed with fetal alcohol spectrum disorders (FASD). In this study, FASD model rats were intragastrically intubated with ethanol (5g/kg/day; 5E), sham-intubated (SI), or maintained as naïve controls (NC) over postnatal days (PD) 4-9. Ethanol exposure during this human third trimester-equivalent period induces persistent impairments in hippocampus-dependent learning and memory. The ability of ibuprofen (IBU), a non-steroidal anti-inflammatory drug, to diminish ethanol-induced neuroinflammation and rescue deficits in hippocampus-dependent trace fear conditioning (TFC) was investigated in 5E rats. Phosphate buffered saline vehicle (VEH) or IBU was injected 2h following ethanol exposure over PD4-9, followed by quantification of inflammation-related genes in the dorsal hippocampus of PD10 rats. The 5E-VEH rats exhibited significant increases in Il1b and Tnf, but not Itgam or Gfap, relative to NC, SI-VEH, and 5E-IBU rats. In separate groups of PD31-33 rats, conditioned fear (freezing) was significantly reduced in 5E-VEH rats during TFC testing, but not acquisition, compared to SI-VEH and, critically, 5E-IBU rats. Results suggest neuroimmune activation in response to ethanol within the neonate hippocampus contributes to later-life cognitive dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of environmental enrichment on behavioral deficits and alterations in hippocampal BDNF induced by prenatal exposure to morphine in juvenile rats.

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Ahmadalipour, A; Sadeghzadeh, J; Vafaei, A A; Bandegi, A R; Mohammadkhani, R; Rashidy-Pour, A

2015-10-01

Prenatal morphine exposure throughout pregnancy can induce a series of neurobehavioral and neurochemical disturbances by affecting central nervous system development. This study was designed to investigate the effects of an enriched environment on behavioral deficits and changes in hippocampal brain-derived neurotrophic factor (BDNF) levels induced by prenatal morphine in rats. On pregnancy days 11-18, female Wistar rats were randomly injected twice daily with saline or morphine. Offspring were weaned on postnatal day (PND) 21. They were subjected to a standard rearing environment or an enriched environment on PNDs 22-50. On PNDs 51-57, the behavioral responses including anxiety and depression-like behaviors, and passive avoidance memory as well as hippocampal BDNF levels were investigated. The light/dark (L/D) box and elevated plus maze (EPM) were used for the study of anxiety, forced swimming test (FST) was used to assess depression-like behavior and passive avoidance task was used to evaluate learning and memory. Prenatal morphine exposure caused a reduction in time spent in the EPM open arms and a reduction in time spent in the lit side of the L/D box. It also decreased step-through latency and increased time spent in the dark side of passive avoidance task. Prenatal morphine exposure also reduced immobility time and increased swimming time in FST. Postnatal rearing in an enriched environment counteracted with behavioral deficits in the EPM and passive avoidance task, but not in the L/D box. This suggests that exposure to an enriched environment during adolescence period alters anxiety profile in a task-specific manner. Prenatal morphine exposure reduced hippocampal BDNF levels, but enriched environment significantly increased BDNF levels in both saline- and morphine-exposed groups. Our results demonstrate that exposure to an enriched environment alleviates behavioral deficits induced by prenatal morphine exposure and up-regulates the decreased levels of BDNF

How to find the way out from four rooms? The learning of "chaining" associations may shed light on the neuropsychology of the deficit syndrome of schizophrenia.

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Polgár, Patricia; Farkas, Márta; Nagy, Orsolya; Kelemen, Oguz; Réthelyi, János; Bitter, István; Myers, Catherine E; Gluck, Mark A; Kéri, Szabolcs

2008-02-01

Recent meta-analytic evidence suggests that clinical neuropsychological methods are not likely to uncover circumscribed cognitive impairments in the deficit syndrome of schizophrenia. To overcome this issue, we adapted a cognitive neuroscience perspective and used a new "chaining" habit learning task. Participants were requested to navigate a cartoon character through a sequence of 4 rooms by learning to choose the open door from 3 colored doors in each room. The aim of the game was to learn the full sequence of rooms until the character reached the outside. In the training phase, each stimulus leading to reward (open door in each room) was trained via feedback until the complete sequence was learned. In the probe phase, the context of rewarded stimuli was manipulated: in a given room, in addition to the correct door of that room, there also appeared a door which was open in another room. Whereas the training phase is dominantly related to basal ganglia circuits, the context-dependent probe phase requires intact medial-temporal lobe functioning. Results revealed that deficit and non-deficit patients were similarly impaired on the probe phase compared with controls. However, the training phase was only compromised in deficit patients. More severe negative symptoms were associated with more errors on the training phase. Executive functions were unrelated to performance on the "chaining" task. These results indicate that the deficit syndrome is associated with prominently impaired stimulus-response reinforcement learning, which may indicate abnormal functioning of basal ganglia circuits.

Inactivation of basolateral amygdala prevents chronic immobilization stress-induced memory impairment and associated changes in corticosterone levels.

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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

Gestational methylazoxymethanol exposure leads to NMDAR dysfunction in hippocampus during early development and lasting deficits in learning.

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Snyder, Melissa A; Adelman, Alicia E; Gao, Wen-Jun

2013-01-01

The N-methyl-D-aspartate (NMDA) receptor has long been associated with learning and memory processes as well as diseased states, particularly in schizophrenia (SZ). Additionally, SZ is increasingly recognized as a neurodevelopmental disorder with cognitive impairments often preceding the onset of psychosis. However, the cause of these cognitive deficits and what initiates the pathological process is unknown. Growing evidence has implicated the glutamate system and, in particular, N-methyl-D-aspartate receptor (NMDAR) dysfunction in the pathophysiology of SZ. Yet, the vast majority of SZ-related research has focused on NMDAR function in adults leaving the role of NMDARs during development uncharacterized. We used the prenatal methylazoxymethanol acetate (MAM, E17) exposure model to determine the alterations of NMDAR protein levels and function, as well as associated cognitive deficits during development. We found that MAM-exposed animals have significantly altered NMDAR protein levels and function in the juvenile and adolescent hippocampus. Furthermore, these changes are associated with learning and memory deficits in the Morris Water Maze. Thus, in the prenatal MAM-exposure SZ model, NMDAR expression and function is altered during the critical period of hippocampal development. These changes may be involved in disease initiation and cognitive impairment in the early stage of SZ.

Simulating Category Learning and Set Shifting Deficits in Patients Weight-Restored from Anorexia Nervosa

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2014-01-01

Neuropsychology, in press     Simulating Category Learning and Set Shifting Deficits in Patients Weight-Restored from Anorexia Nervosa J...University   Objective: To examine set shifting in a group of women previously diagnosed with anorexia nervosa (AN) who are now weight-restored (AN-WR...participant fails to switch to the new rule but rather persists with the previously correct rule. Adult patients with Anorexia Nervosa (AN) are often impaired

Novel-word learning deficits in Mandarin-speaking preschool children with specific language impairments.

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Chen, Yuchun; Liu, Huei-Mei

2014-01-01

Children with SLI exhibit overall deficits in novel word learning compared to their age-matched peers. However, the manifestation of the word learning difficulty in SLI was not consistent across tasks and the factors affecting the learning performance were not yet determined. Our aim is to examine the extent of word learning difficulties in Mandarin-speaking preschool children with SLI, and to explore the potent influence of existing lexical knowledge on to the word learning process. Preschool children with SLI (n=37) and typical language development (n=33) were exposed to novel words for unfamiliar objects embedded in stories. Word learning tasks including the initial mapping and short-term repetitive learning were designed. Results revealed that Mandarin-speaking preschool children with SLI performed as well as their age-peers in the initial form-meaning mapping task. Their word learning difficulty was only evidently shown in the short-term repetitive learning task under a production demand, and their learning speed was slower than the control group. Children with SLI learned the novel words with a semantic head better in both the initial mapping and repetitive learning tasks. Moderate correlations between stand word learning performances and scores on standardized vocabulary were found after controlling for children's age and nonverbal IQ. The results suggested that the word learning difficulty in children with SLI occurred in the process of establishing a robust phonological representation at the beginning stage of word learning. Also, implicit compound knowledge is applied to aid word learning process for children with and without SLI. We also provide the empirical data to validate the relationship between preschool children's word learning performance and their existing receptive vocabulary ability. Copyright © 2013 Elsevier Ltd. All rights reserved.

Betacyanins from Portulaca oleracea L. ameliorate cognition deficits and attenuate oxidative damage induced by D-galactose in the brains of senescent mice.

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Wang, Chang-Quan; Yang, Gui-Qin

2010-06-01

This experiment was designed to assess the protective effect of betacyanins from Portulaca oleracea L. against the D-galactose (D-gal)-induced neurotoxicity in mice. Betacyanins from Portulaca oleracea markedly reversed the D-gal-induced learning and memory impairments, as measured by behavioral tests. The activities of superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in D-gal-treated mice were enhanced, while the content of the lipid peroxidation product malondialdehyde (MDA) was decreased by betacyanin administration. Furthermore, significant negative correlations were found between mouse latency in finding the platform and the activities of SOD, CAT GR and GPx in the mouse brain, but the level of MDA correlated positively with the latency. These results suggest that the neuroprotective effect of betacyanins against D-gal-induced neurotoxicity might be caused, at least in part, by an increase in the activities of antioxidant enzymes with a reduction in lipid peroxidation. In comparison with vitamin C (VC), the betacyanins had a more pronounced effect on ameliorating cognition deficits in mice.

Attention Deficit Hyperactivity Disorder and Tuberous Sclerosis Complex

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... Privacy Policy Sitemap Learn Engage Donate About TSC Attention Deficit Hyperactivity Disorder and TSC What is ADHD? Attention Deficit Hyperactivity Disorder (ADHD) is a common neurobehavioral disorder. It is ...

Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia.

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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.

Effects of resocialization on post-weaning social isolation-induced abnormal aggression and social deficits in rats.

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Tulogdi, Aron; Tóth, Máté; Barsvári, Beáta; Biró, László; Mikics, Eva; Haller, József

2014-01-01

As previously shown, rats isolated from weaning develop abnormal social and aggressive behavior characterized by biting attacks targeting vulnerable body parts of opponents, reduced attack signaling, and increased defensive behavior despite increased attack counts. Here we studied whether this form of violent aggression could be reversed by resocialization in adulthood. During the first weak of resocialization, isolation-reared rats showed multiple social deficits including increased defensiveness and decreased huddling during sleep. Deficits were markedly attenuated in the second and third weeks. Despite improved social functioning in groups, isolated rats readily showed abnormal features of aggression in a resident-intruder test performed after the 3-week-long resocialization. Thus, post-weaning social isolation-induced deficits in prosocial behavior were eliminated by resocialization during adulthood, but abnormal aggression was resilient to this treatment. Findings are compared to those obtained in humans who suffered early social maltreatment, and who also show social deficits and dysfunctional aggression in adulthood. © 2013 Wiley Periodicals, Inc.

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.

Coding deficits in noise-induced hidden hearing loss may stem from incomplete repair of ribbon synapses in the cochlea

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Lijuan eShi

2016-05-01

Full Text Available Recent evidence has shown that noise-induced damage to the synapse between inner hair cells (IHCs and type I afferent auditory nerve fibers (ANFs may occur in the absence of permanent threshold shift (PTS, and that synapses connecting IHCs with low spontaneous rate (SR ANFs are disproportionately affected. Due to the functional importance of low-SR ANF units for temporal processing and signal coding in noisy backgrounds, deficits in cochlear coding associated with noise-induced damage may result in significant difficulties with temporal processing and hearing in noise (i.e., hidden hearing loss. However, significant noise-induced coding deficits have not been reported at the single unit level following the loss of low-SR units. We have found evidence to suggest that some aspects of neural coding are not significantly changed with the initial loss of low-SR ANFs, and that further coding deficits arise in association with the subsequent reestablishment of the synapses. This suggests that synaptopathy in hidden hearing loss may be the result of insufficient repair of disrupted synapses, and not simply due to the loss of low-SR units. These coding deficits include decreases in driven spike rate for intensity coding as well as several aspects of temporal coding: spike latency, peak-to-sustained spike ratio and the recovery of spike rate as a function of click-interval.

Attenuation of ketamine-induced impairment in verbal learning and memory in healthy volunteers by the AMPA receptor potentiator PF-04958242.

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Ranganathan, M; DeMartinis, N; Huguenel, B; Gaudreault, F; Bednar, M M; Shaffer, C L; Gupta, S; Cahill, J; Sherif, M A; Mancuso, J; Zumpano, L; D'Souza, D C

2017-11-01

There is a need to develop treatments for cognitive impairment associated with schizophrenia (CIAS). The significant role played by N-methyl-d-aspartate receptors (NMDARs) in both the pathophysiology of schizophrenia and in neuronal plasticity suggests that facilitation of NMDAR function might ameliorate CIAS. One strategy to correct NMDAR hypofunction is to stimulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as AMPAR and NMDAR functioning are coupled and interdependent. In rats and nonhuman primates (NHP), AMPAR potentiators reduce spatial working memory deficits caused by the nonselective NMDAR antagonist ketamine. The current study assessed whether the AMPAR potentiator PF-04958242 would attenuate ketamine-induced deficits in verbal learning and memory in humans. Healthy male subjects (n=29) participated in two randomized treatment periods of daily placebo or PF-04958242 for 5 days separated by a washout period. On day 5 of each treatment period, subjects underwent a ketamine infusion for 75 min during which the effects of PF-04958242/placebo were assessed on ketamine-induced: (1) impairments in verbal learning and recall measured by the Hopkins Verbal Learning Test; (2) impairments in working memory on a CogState battery; and (3) psychotomimetic effects measured by the Positive and Negative Syndrome Scale and Clinician-Administered Dissociative Symptoms Scale. PF-04958242 significantly reduced ketamine-induced impairments in immediate recall and the 2-Back and spatial working memory tasks (CogState Battery), without significantly attenuating ketamine-induced psychotomimetic effects. There were no pharmacokinetic interactions between PF-04958242 and ketamine. Furthermore, PF-04958242 was well tolerated. 'High-impact' AMPAR potentiators like PF-04958242 may have a role in the treatment of the cognitive symptoms, but not the positive or negative symptoms, associated with schizophrenia. The excellent concordance between the

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.

Linguistic coding deficits in foreign language learners.

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Sparks, R; Ganschow, L; Pohlman, J

1989-01-01

As increasing numbers of colleges and universities require a foreign language for graduation in at least one of their degree programs, reports of students with difficulties in learning a second language are multiplying. Until recently, little research has been conducted to identify the nature of this problem. Recent attempts by the authors have focused upon subtle but ongoing language difficulties in these individuals as the source of their struggle to learn a foreign language. The present paper attempts to expand upon this concept by outlining a theoretical framework based upon a linguistic coding model that hypothesizes deficits in the processing of phonological, syntactic, and/or semantic information. Traditional psychoeducational assessment batteries of standardized intelligence and achievement tests generally are not sensitive to these linguistic coding deficits unless closely analyzed or, more often, used in conjunction with a more comprehensive language assessment battery. Students who have been waived from a foreign language requirement and their proposed type(s) of linguistic coding deficits are profiled. Tentative conclusions about the nature of these foreign language learning deficits are presented along with specific suggestions for tests to be used in psychoeducational evaluations.

Salubrious effects of oxytocin on social stress-induced deficits

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Smith, Adam S.; Wang, Zuoxin

2012-01-01

Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health. PMID:22178036

Conjugated Linoleic Acid Administration Induces Amnesia in Male Sprague Dawley Rats and Exacerbates Recovery from Functional Deficits Induced by a Controlled Cortical Impact Injury.

Directory of Open Access Journals (Sweden)

Rastafa I Geddes

Full Text Available Long-chain polyunsaturated fatty acids like conjugated linoleic acids (CLA are required for normal neural development and cognitive function and have been ascribed various beneficial functions. Recently, oral CLA also has been shown to increase testosterone (T biosynthesis, which is known to diminish traumatic brain injury (TBI-induced neuropathology and reduce deficits induced by stroke in adult rats. To test the impact of CLA on cognitive recovery following a TBI, 5-6 month old male Sprague Dawley rats received a focal injury (craniectomy + controlled cortical impact (CCI; n = 17 or Sham injury (craniectomy alone; n = 12 and were injected with 25 mg/kg body weight of Clarinol® G-80 (80% CLA in safflower oil; n = 16 or saline (n = 13 every 48 h for 4 weeks. Sham surgery decreased baseline plasma progesterone (P4 by 64.2% (from 9.5 ± 3.4 ng/mL to 3.4 ± 0.5 ng/mL; p = 0.068, T by 74.6% (from 5.9 ± 1.2 ng/mL to 1.5 ± 0.3 ng/mL; p 0.05 animals by post-injury day 29, but rapidly reversed by post-injury day 1 the hypoadrenalism in Sham (11-DOC: 372.6 ± 36.6 ng/mL; corticosterone: 202.6 ± 15.6 ng/mL and CCI-injured (11-DOC: 384.2 ± 101.3 ng/mL; corticosterone: 234.6 ± 43.8 ng/mL animals. In Sham surgery animals, CLA did not alter body weight, but did markedly increase latency to find the hidden Morris Water Maze platform (40.3 ± 13.0 s compared to saline treated Sham animals (8.8 ± 1.7 s. In CCI injured animals, CLA did not alter CCI-induced body weight loss, CCI-induced cystic infarct size, or deficits in rotarod performance. However, like Sham animals, CLA injections exacerbated the latency of CCI-injured rats to find the hidden MWM platform (66.8 ± 10.6 s compared to CCI-injured rats treated with saline (30.7 ± 5.5 s, p < 0.05. These results indicate that chronic treatment of CLA at a dose of 25 mg/kg body weight in adult male rats over 1-month 1 does not reverse craniectomy- and craniectomy + CCI-induced hypogonadism, but does reverse

Digital Learning in the Wild: Re-Imagining New Ruralism, Digital Equity, and Deficit Discourses through the Thirdspace

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Cirell, Anna Montana

2017-01-01

Digital media is becoming increasingly important to learning in today's changing times. At the same time, digital technologies and related digital skills are unevenly distributed. Further, deficit-based notions of this digital divide define the public's educational paradigm. Against this backdrop, I forayed into the social reality of one rural…

Lack of strategy holding: a new pattern of learning deficit in cortical dementias.

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Benedet, María J; Lauro-Grotto, Rosapia; Giotti, Chiara

2009-09-01

The aim of this study was to demonstrate, by means of systematic research and qualitative data analysis, the presence, among a group of patients with fronto-temporal lobar degeneration of a subgroup that, at variance with the standard pattern, is able to devise and implement learning strategies, but appear impaired at carrying them on from a trial to the next. In order to provide evidence of the existence of a group of patients showing this type of learning disability, that we refer to as lack of strategy holding, we performed a stepwise hierarchical cluster analysis of a set of variables whose scores were selected from the subject's performance at the Test de Aprendizaje Verbal España-Complutense. Results substantiate the segregation of three groups of subjects characterized by the following patterns of performance: normal elderly individuals, who show a quite preserved ability to discover a semantic strategy along the learning trials and to carry it from a trial to the next, patients presenting with a deficit in implementing semantic learning strategies and possibly use of serial and/or phonological strategies to perform the task, and to patients who, although able to generate and implement appropriate learning strategies, appear unable to carry them over the learning trials. The presence of this new pattern raises a few questions that seem worth trying to address.

Brevican-deficient mice display impaired hippocampal CA1 long-term potentiation but show no obvious deficits in learning and memory

DEFF Research Database (Denmark)

Brakebusch, Cord; Seidenbecher, Constanze I; Asztely, Fredrik

2002-01-01

to be less prominent in mutant than in wild-type mice. Brevican-deficient mice showed significant deficits in the maintenance of hippocampal long-term potentiation (LTP). However, no obvious impairment of excitatory and inhibitory synaptic transmission was found, suggesting a complex cause for the LTP defect....... Detailed behavioral analysis revealed no statistically significant deficits in learning and memory. These data indicate that brevican is not crucial for brain development but has restricted structural and functional roles....

Proof of the mysterious efficacy of ginseng: basic and clinical trials: effects of red ginseng on learning and memory deficits in an animal model of amnesia.

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Nishijo, Hisao; Uwano, Teruko; Zhong, Yong-Mei; Ono, Taketoshi

2004-06-01

Ameliorating effects of red ginseng on learning and memory deficits due to hippocampal lesions and aging were reviewed; the performance of young rats with selective hippocampal lesions with or without red ginseng (p.o.), and aged rats with or without red ginseng (p.o.) in the spatial learning tasks was compared with that of sham-operated or intact young rats. Each rat was tested with 3 types of spatial learning tasks (distance movement task, DMT; random reward place search task, RRPST; and place learning task, PLT) in a circular open field using intracranial self-stimulation (ICSS) as reward. The results in the DMT and RRPST indicated that motivational and motor activity of young rats with hippocampal lesions with and without ginseng and aged rats with and without ginseng were not significantly different from that of control young rats. However, young rats with hippocampal lesions without ginseng and aged rats without ginseng displayed significant deficits in the PLT. Treatment with red ginseng significantly ameliorated place-navigation deficits in young rats with hippocampal lesions in the PLT. Similarly, red ginseng improved performance of aged rats in the PLT. The results, along with previous studies showing significant effects of red ginseng on the central nervous system, suggest that red ginseng ameliorates learning and memory deficits through effects on the central nervous system, partly through effects on the hippocampal formation. However, its mechanisms are still unclear, and further studies are required.

Animal model of dementia induced by entorhinal synaptic damage and partial restoration of cognitive deficits by BDNF and carnitine.

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Ando, Susumu; Kobayashi, Satoru; Waki, Hatsue; Kon, Kazuo; Fukui, Fumiko; Tadenuma, Tomoko; Iwamoto, Machiko; Takeda, Yasuo; Izumiyama, Naotaka; Watanabe, Kazutada; Nakamura, Hiroaki

2002-11-01

A rat dementia model with cognitive deficits was generated by synapse-specific lesions using botulinum neurotoxin (BoNTx) type B in the entorhinal cortex. To detect cognitive deficits, different tasks were needed depending upon the age of the model animals. Impaired learning and memory with lesions were observed in adult rats using the Hebb-Williams maze, AKON-1 maze and a continuous alternation task in T-maze. Cognitive deficits in lesioned aged rats were detected by a continuous alternation and delayed non-matching-to-sample tasks in T-maze. Adenovirus-mediated BDNF gene expression enhanced neuronal plasticity, as revealed by behavioral tests and LTP formation. Chronic administration of carnitine over time pre- and post-lesions seemed to partially ameliorate the cognitive deficits caused by the synaptic lesion. The carnitine-accelerated recovery from synaptic damage was observed by electron microscopy. These results demonstrate that the BoNTx-lesioned rat can be used as a model for dementia and that cognitive deficits can be alleviated in part by BDNF gene transfer or carnitine administration. Copyright 2002 Wiley-Liss, Inc.

A Comparison of Neuropsychological Test Profiles of Children with Attention Deficit-Hyperactivity Disorder and/or Learning Disorder.

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Korkman, Marit; Pesonen, Aino-Elina

1994-01-01

Comparison of eight-year-old children with attention deficit hyperactivity disorder (ADHD) (n=21), learning disorder (LD) (n=12), or both (n=27) on neuropsychological measures found that ADHD children were impaired in control and inhibition of impulses; children with LD in phonological awareness, verbal memory span, storytelling, and verbal IQ;…

The CRF1 and the CRF2 receptor mediate recognition memory deficits and vulnerability induced by opiate withdrawal.

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Morisot, Nadège; Contarino, Angelo

2016-06-01

Opiate use disorders are associated with impaired cognitive function and altered stress-responsive systems. The corticotropin-releasing factor (CRF) system mediates stress responses via CRF1 and CRF2 receptors and may be implicated in substance use disorders. However, the specific role for each of the two known CRF receptor subtypes in cognitive impairment induced by opiate administration and withdrawal remains to be elucidated. In the present study, CRF1-/-, CRF2-/- and their respective wild-type mice are injected with escalating doses of morphine and cognitive function assessed by the novel object recognition (NOR) memory task throughout relatively long periods of opiate withdrawal. Early (2 days) phases of opiate withdrawal impair NOR memory in wild-type, CRF1-/- and CRF2-/- mice. However, the duration of opiate withdrawal-induced NOR memory deficits is prolonged in CRF1-/- but shortened in CRF2-/- mice, as compared to their respective wild-type mice, indicating opposite roles for the two CRF receptor subtypes. Nevertheless, following apparent recovery, exposure to an environmental stressor induces the reemergence of NOR memory deficits in long-term opiate-withdrawn wild-type but not CRF1-/- or CRF2-/- mice, indicating an essential role for both CRF receptor subtypes in stress vulnerability. These findings bring initial evidence of a complex physiopathological role for the CRF system in cognitive deficits and the long-lasting vulnerability induced by opiate drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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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.

Chronic early postnatal scream sound stress induces learning deficits and NMDA receptor changes in the hippocampus of adult mice.

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Hu, Lili; Han, Bo; Zhao, Xiaoge; Mi, Lihua; Song, Qiang; Wang, Jue; Song, Tusheng; Huang, Chen

2016-04-13

Chronic scream sounds during adulthood affect spatial learning and memory, both of which are sexually dimorphic. The long-term effects of chronic early postnatal scream sound stress (SSS) during postnatal days 1-21 (P1-P21) on spatial learning and memory in adult mice as well as whether or not these effects are sexually dimorphic are unknown. Therefore, the present study examines the performance of adult male and female mice in the Morris water maze following exposure to chronic early postnatal SSS. Hippocampal NR2A and NR2B levels as well as NR2A/NR2B subunit ratios were tested using immunohistochemistry. In the Morris water maze, stress males showed greater impairment in spatial learning and memory than background males; by contrast, stress and background females performed equally well. NR2B levels in CA1 and CA3 were upregulated, whereas NR2A/NR2B ratios were downregulated in stressed males, but not in females. These data suggest that chronic early postnatal SSS influences spatial learning and memory ability, levels of hippocampal NR2B, and NR2A/NR2B ratios in adult males. Moreover, chronic early stress-induced alterations exert long-lasting effects and appear to affect performance in a sex-specific manner.

Role of phosphoinositide 3-kinase in ischemic postconditioning-induced attenuation of cerebral ischemia-evoked behavioral deficits in mice.

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Rehni, Ashish K; Singh, Nirmal

2007-01-01

The present study has been designed to pharmacologically investigate the role of phosphoinositide 3-kinase in ischemic postconditioning-induced reversal of global cerebral ischemia and reperfusion-induced behavioral dysfunction in mice. Bilateral carotid artery occlusion for 10 min followed by reperfusion for 24 h was employed in the present study to produce ischemia and reperfusion-induced cerebral injury in mice. Short-term memory was evaluated using the elevated plus maze test. The inclined beam walking test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced impaired short-term memory, motor co-ordination and lateral push response. Three episodes of carotid artery occlusion for a period of 10 s and reperfusion of 10 s (ischemic postconditioning) significantly prevented ischemia-reperfusion-induced behavioral deficit measured in terms of loss of short-term memory, motor coordination and lateral push response. Wortmannin (2 mg/kg, iv), a phosphoinositide 3-kinase inhibitor given 10 min before ischemia attenuated the beneficial effects of ischemic postconditioning. It may be concluded that beneficial effects of ischemic postconditioning on global cerebral ischemia and reperfusion-induced behavioral deficits may involve activation of phosphoinositide 3-kinase-linked pathway.

Methylmercury chloride induces learning deficits in prenatally treated rats

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Muesch, H.R.; Bornhausen, M.; Kriegel, H.; Greim, H.

1978-01-01

Methylmercury chloride (MMC) was given to pregnant rats on the 6th, 7th, 8th, and 9th day after conception in doses of 0.05 and 2.0 mg/kg/day. The female offspring of these animals were tested 90 days after birth for learning ability using operant conditioning procedures. The rats were kept at 90% of their normal body weight and trained in a lever-box to press a bar in order to obtain a food pellet. Significant differences in the acquisition speed became apparent when the ratio of bar presses to reward was increased in a classical contingency of differential reinforcement of high rates even at MMC-doses of 4 x 0.05 mg/kg. These differences were not found in the general motility level nor in motor coordination.

Inducible forebrain-specific ablation of the transcription factor Creb during adulthood induces anxiety but no spatial/contextual learning deficits

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Miriam Annika Vogt

2014-11-01

Full Text Available The cyclic AMP (cAMP-response element binding protein (CREB is an activity-dependent transcription factor playing a role in synaptic plasticity, learning and memory, and emotional behavior. However, the impact of Creb ablation on rodent behavior is vague as e.g. memory performance of different Creb mutant mice depends on the specific type of mutation per se but additionally on the background and learning protocol differences. Here we present the first targeted ablation of CREB induced during adulthood selectively in principal forebrain neurons in a pure background strain of C57BL/6 mice. All hippocampal principal neurons exhibited lack of CREB expression. Mutant mice showed a severe anxiety phenotype in the openfield and novel object exploration test as well as in the Dark-Light Box Test, but unaltered hippocampus-dependent long-term memory in the Morris water maze and in context dependent fear conditioning. On the molecular level, CREB ablation led to CREM up regulation in the hippocampus and frontal cortex which may at least in part compensate for the loss of CREB. BDNF, a postulated CREB target gene, was down regulated in the frontal lobe but not in the hippocampus; neurogenesis remained unaltered. Our data indicate that in the adult mouse forebrain the late onset of CREB ablation can, in case of memory functionality, be compensated for and is not essential for memory consolidation and retrieval during adulthood. In contrast, the presence of CREB protein during adulthood seems to be pivotal for the regulation of emotional behavior.

Neonatal infection produces significant changes in immune function with no associated learning deficits in juvenile rats.

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Osborne, Brittany F; Caulfield, Jasmine I; Solomotis, Samantha A; Schwarz, Jaclyn M

2017-10-01

The current experiments examined the impact of early-life immune activation and a subsequent mild immune challenge with lipopolysaccharide (LPS; 25µg/kg) on hippocampal-dependent learning, proinflammatory cytokine expression in the brain, and peripheral immune function in juvenile male and female rats at P24, an age when hippocampal-dependent learning and memory first emerges. Our results indicate that neonatal infection did not produce learning deficits in the hippocampal-dependent context pre-exposure facilitation effect paradigm in juvenile males and females, contrary to what has been observed in adults. Neonatal infection produced an increase in baseline IL-1β expression in the hippocampus (HP) and medial prefrontal cortex (mPFC) of juvenile rats. Furthermore, neonatally infected rats showed exaggerated IL-1β expression in the HP following LPS treatment as juveniles; and juvenile females, but not males, showed exaggerated IL-1β expression in the mPFC following LPS treatment. Neonatal infection attenuated the production of IL-6 expression following LPS treatment in both the brain and the spleen, and neonatal infection decreased the numbers of circulating white blood cells in juvenile males and females, an effect that was further exacerbated by subsequent LPS treatment. Together, our data indicate that the consequences of neonatal infection are detectable even early in juvenile development, though we found no concomitant hippocampal-dependent learning deficits at this young age. These findings underscore the need to consider age and associated on-going neurodevelopmental processes as important factors contributing to the emergence of cognitive and behavioral disorders linked to early-life immune activation. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1221-1236, 2017. © 2017 Wiley Periodicals, Inc.

Support for Learning Goes beyond Academic Support: Voices of Students with Asperger's Disorder and Attention Deficit Hyperactivity Disorder

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Bolic Baric, Vedrana; Hellberg, Kristina; Kjellberg, Anette; Hemmingsson, Helena

2016-01-01

The purpose of this study was to describe and explore the experiences of support at school among young adults with Asperger's disorder and attention deficit hyperactivity disorder and also to examine what support they, in retrospect, described as influencing learning. Purposive sampling was used to enroll participants. Data were collected through…

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

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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.

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

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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.

Effect of kai xin san on learning and memory in a rat model of paradoxical sleep deprivation.

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Hu, Yuan; Liu, Ming; Liu, Ping; Yan, Juan-Juan; Liu, Ming-Yue; Zhang, Gang-Qiang; Zhou, Xiao-Jiang; Yu, Bing-Ying

2013-04-01

The present study aimed to evaluate the effect of kai xin san (KXS, at doses of 500, 250, and 125 mg/kg body weight per day), a well-known traditional Chinese medicine, on learning and memory in paradoxical sleep deprivation (PSD)-induced cognition deficit rats. Two behavior tests (the Open Field test and the Morris water maze task) were used for testing the effects of KXS on a PSD-induced learning and memory deficit model. Furthermore, its effect on the glutamic acid (GLU) and γ-amino-butyric acid (GABA) levels in the brain tissue, brain-derived neurotrophic factor (BDNF), cyclic AMP response element binding protein (CREB), and phosphorylated-CREB (p-CREB) expression in the hippocampus was also tested. KXS exerted the greatest cognition against the 48 h PSD-induced cognitive deficit and these effects may be mediated by decreasing the GLU and GABA levels and increasing the levels of BDNF, CREB, and p-CREB. This study indicates that the effect of KXS on learning and memory in a rat model of PSD could be associated with the modulation of neurotransmitter levels and the expression of some genes in the brain that contribute to memory functions.

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

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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.

Development and evaluation of the LiSN & learn auditory training software for deficit-specific remediation of binaural processing deficits in children: preliminary findings.

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Cameron, Sharon; Dillon, Harvey

2011-01-01

The LiSN & Learn auditory training software was developed specifically to improve binaural processing skills in children with suspected central auditory processing disorder who were diagnosed as having a spatial processing disorder (SPD). SPD is defined here as a condition whereby individuals are deficient in their ability to use binaural cues to selectively attend to sounds arriving from one direction while simultaneously suppressing sounds arriving from another. As a result, children with SPD have difficulty understanding speech in noisy environments, such as in the classroom. To develop and evaluate the LiSN & Learn auditory training software for children diagnosed with the Listening in Spatialized Noise-Sentences Test (LiSN-S) as having an SPD. The LiSN-S is an adaptive speech-in-noise test designed to differentially diagnose spatial and pitch-processing deficits in children with suspected central auditory processing disorder. Participants were nine children (aged between 6 yr, 9 mo, and 11 yr, 4 mo) who performed outside normal limits on the LiSN-S. In a pre-post study of treatment outcomes, participants trained on the LiSN & Learn for 15 min per day for 12 weeks. Participants acted as their own control. Participants were assessed on the LiSN-S, as well as tests of attention and memory and a self-report questionnaire of listening ability. Performance on all tasks was reassessed after 3 mo where no further training occurred. The LiSN & Learn produces a three-dimensional auditory environment under headphones on the user's home computer. The child's task was to identify a word from a target sentence presented in background noise. A weighted up-down adaptive procedure was used to adjust the signal level of the target based on the participant's response. On average, speech reception thresholds on the LiSN & Learn improved by 10 dB over the course of training. As hypothesized, there were significant improvements in posttraining performance on the LiSN-S conditions

Effect of vitamin E on lead exposure-induced learning and memory impairment in rats.

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Khodamoradi, Nasrin; Komaki, Alireza; Salehi, Iraj; Shahidi, Siamak; Sarihi, Abdolrahman

2015-05-15

Chronic lead (Pb(2+)) exposure has been associated with learning and memory impairments, whereas vitamin E improves cognitive deficits. In this study, using a passive avoidance learning model in rats, we investigated the effects of vitamin E on Pb(2+) exposure-induced learning and memory impairments in rats. In the present study, 56 Wistar male rats (weighting 230-250g) were divided into eight groups (n=7). The Pb(2+) exposure involved gavages of lead acetate solution using three different doses (0.05%, 0.1%, and 0.2%) and the vitamin E consisted of three different doses (10, 25, 50μg/rat) for 30days. After the 30-day period, the rats were tested using a passive avoidance task (acquisition test). In a retrieval test conducted 48h after the training, step through latency (STL) and time in the dark compartment (TDC) were recorded. The statistical analysis of data was performed using ANOVA followed by Tukey's post hoc analysis. In all cases, differences were considered significant if plearning and the TDC, whereas it decreased the STL in the passive avoidance test. Administration of vitamin E ameliorated the effects of Pb(2+) on animal behavior in the passive avoidance learning and memory task. Our results indicate that impairments of learning and memory in Pb(2+)-exposed rats are dose dependent and can be inhibited by antioxidants such as vitamin E. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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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.

Gypenosides ameliorate memory deficits in MPTP-lesioned mouse model of Parkinson's disease treated with L-DOPA.

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Zhao, Ting Ting; Kim, Kyung Sook; Shin, Keon Sung; Park, Hyun Jin; Kim, Hyun Jeong; Lee, Kyung Eun; Lee, Myung Koo

2017-09-06

Previous studies have revealed that gypenosides (GPS) improve the symptoms of anxiety disorders in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rat model of Parkinson's disease (PD). The present study aimed to investigate the effects of GPS on memory deficits in an MPTP-lesioned mouse model of PD treated with L-3,4-dihydroxyphenylalanine (L-DOPA). MPTP (30 mg/kg/day, 5 days)-lesioned mice were treated with GPS (50 mg/kg) and/or L-DOPA (10 and 25 mg/kg) for 21 days. After the final treatments, behavioral changes were assessed in all mice using passive avoidance and elevated plus-maze tests. We then evaluated the biochemical influences of GPS treatment on levels of tyrosine hydroxylase (TH), dopamine, N-methyl-D-aspartate (NMDA) receptors, extracellular signal-regulated kinase (ERK1/2), and cyclic AMP-response element binding protein (CREB) phosphorylation. MPTP-lesioned mice exhibited deficits associated with habit learning and spatial memory, which were further aggravated by treatment with L-DOPA (25 mg/kg). However, treatment with GPS (50 mg/kg) ameliorated memory deficits. Treatment with GPS (50 mg/kg) also improved L-DOPA (25 mg/kg)-treated MPTP lesion-induced decreases in retention latency on the passive avoidance test, as well as levels of TH-immunopositive cells and dopamine in the substantia nigra and striatum. GPS treatment also attenuated increases in retention transfer latency on the elevated plus-maze test and in NMDA receptor expression, as well as decreases in the phosphorylation of ERK1/2 and CREB in the hippocampus. Treatment with L-DOPA (10 mg/kg) also ameliorated deficits in habit learning and spatial memory in MPTP-lesioned mice, and this effect was further enhanced by treatment with GPS (50 mg/kg). GPS ameliorate deficits in habit learning and spatial memory by modulating the dopaminergic neuronal and N-methyl-D-aspartate receptor-mediated signaling systems in MPTP-lesioned mice treated with L-DOPA. GPS may serve as an adjuvant

Adolescent maturational transitions in the prefrontal cortex and dopamine signalling as a risk factor for the development of obesity and high fat / high sugar diet induced cognitive deficits

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Amy Claire Reichelt

2016-10-01

Full Text Available Adolescence poses as both a transitional period in neurodevelopment and lifestyle practices. In particular, the developmental trajectory of the prefrontal cortex, a critical region for behavioural control and self-regulation, is enduring, not reaching functional maturity until the early 20s in humans. Furthermore, the neurotransmitter dopamine is particularly abundant during adolescence, tuning the brain to rapidly learn about rewards and regulating aspects of neuroplasticity. Thus, adolescence is proposed to represent a period of vulnerability towards reward-driven behaviours such as the consumption of palatable high fat and high sugar diets. This is reflected in the increasing prevalence of obesity in children and adolescents as they are the greatest consumers of junk foods. Excessive consumption of diets laden in saturated fat and refined sugars not only leads to weight gain and the development of obesity, but experimental studies with rodents indicate they evoke cognitive deficits in learning and memory process by disrupting neuroplasticity and altering reward processing neurocircuitry. Consumption of these high fat and high sugar diets have been reported to have a particularly pronounced impact on cognition when consumed during adolescence, demonstrating a susceptibility of the adolescent brain to enduring cognitive deficits. The adolescent brain, with heightened reward sensitivity and diminished behavioural control compared to the mature adult brain, appears to be a risk for aberrant eating behaviours that may underpin the development of obesity. This review explores the neurodevelopmental changes in the prefrontal cortex and mesocortical dopamine signalling that occur during adolescence, and how these potentially underpin the overconsumption of palatable food and development of obesogenic diet induced cognitive deficits.

Specific learning disabilities in children: deficits and neuropsychological profile.

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Kohli, Adarsh; Malhotra, Savita; Mohanty, Manju; Khehra, Nitasha; Kaur, Manreet

2005-06-01

The public is gradually becoming aware of specific learning disabilities (SLDs), which are very often the cause of academic difficulties. The aim of the study was to assess the SLDs in the clinic population at the Child and Adolescent Psychiatry Clinic at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh using the National Institute of Mental Health and Neurosciences SLD index and subsequently to assess the children's neuropsychological functions using a battery of tests. Thirty-five children in the age range of 7-14 years (both boys and girls) were recruited as the cohort, diagnosed clinically and assessed using the battery of tests for SLDs and neuropsychological tests consisting of the PGIMER memory scale for children, the Wisconsin card sorting test, the Bender visuo-motor gestalt test and Malin's intelligence scale for Indian children. The study revealed deficits in language and writing skills and impairments in specific areas of memory, executive functions and perceptuo-motor tasks. Identification of SLDs is useful in drawing up a treatment plan specific for a particular child.

Dietary Reversal Ameliorates Short- and Long-Term Memory Deficits Induced by High-fat Diet Early in Life.

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Catrina Sims-Robinson

Full Text Available A high-fat diet (HFD, one of the major factors contributing to metabolic syndrome, which is associated with an increased risk of neurodegenerative diseases, leads to insulin resistance and cognitive impairment. It is not known whether these alterations are improved with dietary intervention. To investigate the long-term impact of a HFD on hippocampal insulin signaling and memory, C57BL6 mice were placed into one of three groups based on the diet: a standard diet (control, a HFD, or a HFD for 16 weeks and then the standard diet for 8 weeks (HF16. HFD-induced impairments in glucose tolerance and hippocampal insulin signaling occurred concurrently with deficits in both short- and long-term memory. Furthermore, these conditions were improved with dietary intervention; however, the HFD-induced decrease in insulin receptor expression in the hippocampus was not altered with dietary intervention. Our results demonstrate that memory deficits due to the consumption of a HFD at an early age are reversible.

Protective effect of lavender oil on scopolamine induced cognitive deficits in mice and H2O2 induced cytotoxicity in PC12 cells.

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Xu, Pan; Wang, Kezhu; Lu, Cong; Dong, Liming; Gao, Li; Yan, Ming; Aibai, Silafu; Liu, Xinmin

2016-12-04

Lavender essential oil (LO), an aromatic liquid extracted from Lavandula angustifolia Mill., has been traditionally used in the treatments of many nervous system diseases, and recently LO also reported to be effective for the Alzheimer's disease (AD). The improvement effect of lavender oil (LO) on the scopolamine-induced cognitive deficits in mice and H 2 O 2 induced cytotoxicity in PC12 cells have been evaluated. The relevant mechanism was also researched from the perspective of antioxidant effect and cholinergic system modulation. Cognitive deficits were induced in C57BL/6J mice treated with scopolamine (1mg/kg, i.p.) and were assessed by Morris water maze (MWM) and step-through passive avoidance tests. Then their hippocampus were removed for biochemical assays (acetylcholinesterase (AChE), superoxide dismutase (SOD), glutathione peroxidase (GPX) and malondialdehyde (MDA)). In vitro, the cytotoxicity were induced by 4h exposure to H 2 O 2 in PC12 and evaluated by cell viability (MTT), lactate dehydrogenase (LDH) level, nitric oxide (NO) release, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP). The results demonstrated that LO (100mg/kg) could improve the cognitive performance of scopolamine induced mice in behavioral tests. Meanwhile, it significantly decreased the AChE activity, MDA level, and increase SOD and GPX activities of the model. Moreover, LO (12μg/mL) protected PC12 cells from H 2 O 2 induced cytotoxicity by reducing LDH, NO release, intracellular ROS accumulation and MMP loss. It was suggested that LO could show neuroprotective effect in AD model in vivo (scopolamine-treated mice) and in vitro (H 2 O 2 induced PC12 cells) via modulating oxidative stress and AChE activity. Copyright © 2016. Published by Elsevier Ireland Ltd.

Differential response to gepirone but not to chlordiazepoxide in malnourished rats subjected to learned helplessness.

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Camargo, L M M; Nascimento, A B; Almeida, S S

2008-01-01

The learned helplessness (LH) paradigm is characterized by learning deficits resulting from inescapable events. The aims of the present study were to determine if protein-calorie malnutrition (PCM) alters learning deficits induced by LH and if the neurochemical changes induced by malnutrition alter the reactivity to treatment with GABA-ergic and serotonergic drugs during LH. Well-nourished (W) and PCM Wistar rats (61 days old) were exposed or not to inescapable shocks (IS) and treated with gepirone (GEP, 0.0-7.5 mg/kg, intraperitoneally, N = 128) or chlordiazepoxide (0.0-7.5 mg/kg, intraperitoneally, N = 128) 72 h later, 30 min before the test session (30 trials of escape learning). The results showed that rats exposed to IS had higher escape latency than non-exposed rats (12.6 +/- 2.2 vs 4.4 +/- 0.8 s) and that malnutrition increased learning impairment produced by LH. GEP increased the escape latency of W animals exposed or non-exposed to IS, but did not affect the response of PCM animals, while chlordiazepoxide reduced the escape deficit of both W and PCM rats. The data suggest that PCM animals were more sensitive to the impairment produced by LH and that PCM led to neurochemical changes in the serotonergic system, resulting in hyporeactivity to the anxiogenic effects of GEP in the LH paradigm.

Differential response to gepirone but not to chlordiazepoxide in malnourished rats subjected to learned helplessness

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L.M.M Camargo

2008-01-01

Full Text Available The learned helplessness (LH paradigm is characterized by learning deficits resulting from inescapable events. The aims of the present study were to determine if protein-calorie malnutrition (PCM alters learning deficits induced by LH and if the neurochemical changes induced by malnutrition alter the reactivity to treatment with GABA-ergic and serotonergic drugs during LH. Well-nourished (W and PCM Wistar rats (61 days old were exposed or not to inescapable shocks (IS and treated with gepirone (GEP, 0.0-7.5 mg/kg, intraperitoneally, N = 128 or chlordiazepoxide (0.0-7.5 mg/kg, intraperitoneally, N = 128 72 h later, 30 min before the test session (30 trials of escape learning. The results showed that rats exposed to IS had higher escape latency than non-exposed rats (12.6 ± 2.2 vs 4.4 ± 0.8 s and that malnutrition increased learning impairment produced by LH. GEP increased the escape latency of W animals exposed or non-exposed to IS, but did not affect the response of PCM animals, while chlordiazepoxide reduced the escape deficit of both W and PCM rats. The data suggest that PCM animals were more sensitive to the impairment produced by LH and that PCM led to neurochemical changes in the serotonergic system, resulting in hyporeactivity to the anxiogenic effects of GEP in the LH paradigm.

Touchscreen learning deficits in Ube3a, Ts65Dn and Mecp2 mouse models of neurodevelopmental disorders with intellectual disabilities.

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Leach, P T; Crawley, J N

2017-12-20

Mutant mouse models of neurodevelopmental disorders with intellectual disabilities provide useful translational research tools, especially in cases where robust cognitive deficits are reproducibly detected. However, motor, sensory and/or health issues consequent to the mutation may introduce artifacts that preclude testing in some standard cognitive assays. Touchscreen learning and memory tasks in small operant chambers have the potential to circumvent these confounds. Here we use touchscreen visual discrimination learning to evaluate performance in the maternally derived Ube3a mouse model of Angelman syndrome, the Ts65Dn trisomy mouse model of Down syndrome, and the Mecp2 Bird mouse model of Rett syndrome. Significant deficits in acquisition of a 2-choice visual discrimination task were detected in both Ube3a and Ts65Dn mice. Procedural control measures showed no genotype differences during pretraining phases or during acquisition. Mecp2 males did not survive long enough for touchscreen training, consistent with previous reports. Most Mecp2 females failed on pretraining criteria. Significant impairments on Morris water maze spatial learning were detected in both Ube3a and Ts65Dn, replicating previous findings. Abnormalities on rotarod in Ube3a, and on open field in Ts65Dn, replicating previous findings, may have contributed to the observed acquisition deficits and swim speed abnormalities during water maze performance. In contrast, these motor phenotypes do not appear to have affected touchscreen procedural abilities during pretraining or visual discrimination training. Our findings of slower touchscreen learning in 2 mouse models of neurodevelopmental disorders with intellectual disabilities indicate that operant tasks offer promising outcome measures for the preclinical discovery of effective pharmacological therapeutics. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

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

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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.

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

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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.

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

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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.

P2X7 Receptor Antagonism Attenuates the Intermittent Hypoxia-induced Spatial Deficits in a Murine Model of Sleep Apnea Via Inhibiting Neuroinflammation and Oxidative Stress

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Yan Deng

2015-01-01

Conclusions: The P2X7R antagonism attenuates the CIH-induced neuroinflammation, oxidative stress, and spatial deficits, demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.

LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone

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Bian, Xuting; Zhong, Hongyu; Li, Fen; Cai, Yulong; Li, Xin; Wang, Lian; Fan, Xiaotang, E-mail: fanxiaotang2005@163.com

2016-09-02

Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects.

LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone

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Bian, Xuting; Zhong, Hongyu; Li, Fen; Cai, Yulong; Li, Xin; Wang, Lian; Fan, Xiaotang

2016-01-01

Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects.

Effect of Neuroscience-Based Cognitive Skill Training on Growth of Cognitive Deficits Associated with Learning Disabilities in Children Grades 2-4

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Avtzon, Sarah Abitbol

2012-01-01

Working memory, executive functions, and cognitive processes associated with specific academic areas, are empirically identified as being the core underlying cognitive deficits in students with specific learning disabilities. Using Hebb's theory of neuroplasticity and the principle of automaticity as theoretical bases, this experimental study…

Selective Activation of M4 Muscarinic Acetylcholine Receptors Reverses MK-801-Induced Behavioral Impairments and Enhances Associative Learning in Rodents

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2015-01-01

Positive allosteric modulators (PAMs) of the M4 muscarinic acetylcholine receptor (mAChR) represent a novel approach for the treatment of psychotic symptoms associated with schizophrenia and other neuropsychiatric disorders. We recently reported that the selective M4 PAM VU0152100 produced an antipsychotic drug-like profile in rodents after amphetamine challenge. Previous studies suggest that enhanced cholinergic activity may also improve cognitive function and reverse deficits observed with reduced signaling through the N-methyl-d-aspartate subtype of the glutamate receptor (NMDAR) in the central nervous system. Prior to this study, the M1 mAChR subtype was viewed as the primary candidate for these actions relative to the other mAChR subtypes. Here we describe the discovery of a novel M4 PAM, VU0467154, with enhanced in vitro potency and improved pharmacokinetic properties relative to other M4 PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801. VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant-induced deficits in M4 KO mice. VU0467154 also enhanced the acquisition of both contextual and cue-mediated fear conditioning when administered alone in wild-type mice. These novel findings suggest that M4 PAMs may provide a strategy for addressing the more complex affective and cognitive disruptions associated with schizophrenia and other neuropsychiatric disorders. PMID:25137629

Specific learning disorder: prevalence and gender differences.

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Kristina Moll

Full Text Available Comprehensive models of learning disorders have to consider both isolated learning disorders that affect one learning domain only, as well as comorbidity between learning disorders. However, empirical evidence on comorbidity rates including all three learning disorders as defined by DSM-5 (deficits in reading, writing, and mathematics is scarce. The current study assessed prevalence rates and gender ratios for isolated as well as comorbid learning disorders in a representative sample of 1633 German speaking children in 3rd and 4th Grade. Prevalence rates were analysed for isolated as well as combined learning disorders and for different deficit criteria, including a criterion for normal performance. Comorbid learning disorders occurred as frequently as isolated learning disorders, even when stricter cutoff criteria were applied. The relative proportion of isolated and combined disorders did not change when including a criterion for normal performance. Reading and spelling deficits differed with respect to their association with arithmetic problems: Deficits in arithmetic co-occurred more often with deficits in spelling than with deficits in reading. In addition, comorbidity rates for arithmetic and reading decreased when applying stricter deficit criteria, but stayed high for arithmetic and spelling irrespective of the chosen deficit criterion. These findings suggest that the processes underlying the relationship between arithmetic and reading might differ from those underlying the relationship between arithmetic and spelling. With respect to gender ratios, more boys than girls showed spelling deficits, while more girls were impaired in arithmetic. No gender differences were observed for isolated reading problems and for the combination of all three learning disorders. Implications of these findings for assessment and intervention of learning disorders are discussed.

Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3β signaling disruption.

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Moosavi, Maryam; Zarifkar, Amir Hossein; Farbood, Yaghoub; Dianat, Mahin; Sarkaki, Alireza; Ghasemi, Rasoul

2014-08-05

Centrally administered streptozotocin (STZ), is known to cause Alzheimer׳s like memory deterioration. It mainly affects insulin signaling pathways such as PI3/Akt and GSK-3β which are involved in cell survival. Previous studies indicate that STZ increases the ratio of Bax/Bcl-2 and thereby induces caspase-3 activation and apoptosis. Agmatine, a polyamine derived from l-arginine decarboxylation, is recently shown to exert some neuroprotective effects. This study aimed to assess if agmatine reverses STZ-induced memory deficits, hippocampal Akt/GSK-3β signaling disruption and caspase-3 activation. Adult male Sprague-Dawely rats weighing 200-250 g were used. The canules were implanted bilaterally into lateral ventricles. STZ was administered on days 1 and 3 (3 mg/kg) and agmatine treatment (40 or 80 mg/kg) was started from day 4 and continued in an every other day manner till day 14. The animal׳s learning and memory capability was assessed on days 15-18 using Morris water maze. After complement of behavioral studies the hippocampi was isolated and the amounts of hippocampal cleaved caspase-3 (the landmark of apoptosis), Bax/Bcl-2 ratio, total and phosphorylated forms of GSK-3β and Akt were analyzed by western blot. The results showed that agmatine in 80 but not 40 mg/kg reversed the memory deterioration induced by STZ. Western blot analysis revealed that STZ prompted elevation of caspase-3; Bax/Bcl-2 ratio and disrupted Akt/GSK-3β signaling in the hippocampus. Agmatine treatment prevented apoptosis and Akt/GSK-3β signaling impairment induced by STZ. This study disclosed that agmatine treatment averts not only STZ-induced memory deterioration but also hippocampal apoptosis and Akt/GSK-3β signaling disruption. Copyright © 2014 Elsevier B.V. All rights reserved.

Nutritional compensation to exercise- vs. diet-induced acute energy deficit in adolescents with obesity

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Thivel , David; Doucet , Eric; Julian , Valérie; Cardenoux , Charlotte; Boirie , Yves; Duclos , Martine

2017-01-01

This article belongs to a special issueConference: 24th Annual Meeting of the Society-for-the-Study-of-Ingestive-Behavior (SSIB)Location: Porto, PORTUGALDate: JUL 12-16, 2016Sponsor(s):Soc Study Ingest BehavThe authors want to thank the adolescents who took part in the study as well as Miss Nais Petiot and Miss Audrey Marion for their help; BACKGROUND: To compare the energy and macronutrient intake responses to equivalent energy deficits induced by diet (food restriction) and exercise in adol...

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

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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 short-term memory ( (53.0 ± 9.2) vs (58.0 ± 9.7) score, P memory domains ((10.0 ± 3.3) vs (11.3 ± 3.5) score, 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 memory, visual reproduction and digit span, ADHD+LD scored significantly lower than the control group (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.

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.

Mori Folium and Mori Fructus Mixture Attenuates High-Fat Diet-Induced Cognitive Deficits in Mice

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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.

Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway

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Ji, Jian-feng; Ji, Sheng-jun; Sun, Rui; Li, Kun; Zhang, Yuan; Zhang, Li-yuan; Tian, Ye

2014-01-01

Highlights: •Forced exercise can ameliorate WBI induced cognitive impairment in our rat model. •Mature BDNF plays an important role in the effects of forced exercise. •Exercise may be a possible treatment of the radiation-induced cognitive impairment. -- Abstract: Cranial radiotherapy induces progressive and debilitating cognitive deficits, particularly in long-term cancer survivors, which may in part be caused by the reduction of hippocampal neurogenesis. Previous studies suggested that voluntary exercise can reduce the cognitive impairment caused by radiation therapy. However, there is no study on the effect of forced wheel exercise and little is known about the molecular mechanisms mediating the effect of exercise. In the present study, we investigated whether the forced running exercise after irradiation had the protective effects of the radiation-induced cognitive impairment. Sixty-four Male Sprague–Dawley rats received a single dose of 20 Gy or sham whole-brain irradiation (WBI), behavioral test was evaluated using open field test and Morris water maze at 2 months after irradiation. Half of the rats accepted a 3-week forced running exercise before the behavior detection. Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis and Western blotting was used to assess changes in the levels of mature brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response element binding protein (CREB) in the BDNF–pCREB signaling. We found forced running exercise significantly prevented radiation-induced cognitive deficits, ameliorated the impairment of hippocampal neurogenesis and attenuated the down-regulation of these proteins. Moreover, exercise also increased behavioral performance, hippocampal neurogenesis and elevated BDNF–pCREB signaling in non

Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway

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Ji, Jian-feng; Ji, Sheng-jun; Sun, Rui; Li, Kun; Zhang, Yuan; Zhang, Li-yuan; Tian, Ye, E-mail: dryetian@hotmail.com

2014-01-10

Highlights: •Forced exercise can ameliorate WBI induced cognitive impairment in our rat model. •Mature BDNF plays an important role in the effects of forced exercise. •Exercise may be a possible treatment of the radiation-induced cognitive impairment. -- Abstract: Cranial radiotherapy induces progressive and debilitating cognitive deficits, particularly in long-term cancer survivors, which may in part be caused by the reduction of hippocampal neurogenesis. Previous studies suggested that voluntary exercise can reduce the cognitive impairment caused by radiation therapy. However, there is no study on the effect of forced wheel exercise and little is known about the molecular mechanisms mediating the effect of exercise. In the present study, we investigated whether the forced running exercise after irradiation had the protective effects of the radiation-induced cognitive impairment. Sixty-four Male Sprague–Dawley rats received a single dose of 20 Gy or sham whole-brain irradiation (WBI), behavioral test was evaluated using open field test and Morris water maze at 2 months after irradiation. Half of the rats accepted a 3-week forced running exercise before the behavior detection. Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis and Western blotting was used to assess changes in the levels of mature brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response element binding protein (CREB) in the BDNF–pCREB signaling. We found forced running exercise significantly prevented radiation-induced cognitive deficits, ameliorated the impairment of hippocampal neurogenesis and attenuated the down-regulation of these proteins. Moreover, exercise also increased behavioral performance, hippocampal neurogenesis and elevated BDNF–pCREB signaling in non

Revealing past memories: proactive interference and ketamine-induced memory deficits.

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Chrobak, James J; Hinman, James R; Sabolek, Helen R

2008-04-23

Memories of events that occur often are sensitive to interference from memories of similar events. Proactive interference plays an important and often unexamined role in memory testing for spatially and temporally unique events ("episodes"). Ketamine (NMDA receptor antagonist) treatment in humans and other mammals induces a constellation of cognitive deficits, including impairments in working and episodic memory. We examined the effects of the ketamine (2.5-100 mg/kg) on the acquisition, retrieval, and retention of memory in a delayed-match-to-place radial water maze task that can be used to assess proactive interference. Ketamine (2.5-25 mg/kg, i.p.) given 20 min before the sample trial, impaired encoding. The first errors made during the test trial were predominantly to arms located spatially adjacent to the goal arm, suggesting an established albeit weakened representation. Ketamine (25-100 mg/kg) given immediately after the sample trial had no effect on retention. Ketamine given before the test trial impaired retrieval. First errors under the influence of ketamine were predominantly to the goal location of the previous session. Thus, ketamine treatment promoted proactive interference. These memory deficits were not state dependent, because ketamine treatment at both encoding and retrieval only increased the number of errors during the test session. These data demonstrate the competing influence of distinct memory representations during the performance of a memory task in the rat. Furthermore, they demonstrate the subtle disruptive effects of the NMDA antagonist ketamine on both encoding and retrieval. Specifically, ketamine treatment disrupted retrieval by promoting proactive interference from previous episodic representations.

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

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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

NCAM deficiency in the mouse forebrain impairs innate and learned avoidance behaviours.

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Brandewiede, J; Stork, O; Schachner, M

2014-06-01

The neural cell adhesion molecule (NCAM) has been implicated in the development and plasticity of neural circuits and the control of hippocampus- and amygdala-dependent learning and behaviour. Previous studies in constitutive NCAM null mutants identified emotional behaviour deficits related to disturbances of hippocampal and amygdala functions. Here, we studied these behaviours in mice conditionally deficient in NCAM in the postmigratory forebrain neurons. We report deficits in both innate and learned avoidance behaviours, as observed in elevated plus maze and passive avoidance tasks. In contrast, general locomotor activity, trait anxiety or neophobia were unaffected by the mutation. Altered avoidance behaviour of the conditional NCAM mutants was associated with a deficit in serotonergic signalling, as indicated by their reduced responsiveness to (±)-8-hydroxy-2-(dipropylamino)-tetralin-induced hypothermia. Another serotonin-dependent behaviour, namely intermale aggression that is massively increased in constitutively NCAM-deficient mice, was not affected in the forebrain-specific mutants. Our data suggest that genetically or environmentally induced changes of NCAM expression in the late postnatal and mature forebrain determine avoidance behaviour and serotonin (5-HT)1A receptor signalling. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Sleep disturbance induces neuroinflammation and impairment of learning and memory.

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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.

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.

Victimization by Bullying and Attachment to Parents and Teachers among Students Who Report Learning Disorders and/or Attention Deficit Hyperactivity Disorder

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Klomek, A. Brunstein; Kopelman-Rubin, D.; Al-Yagon, M.; Berkowitz, Ruth; Apter, A.; Mikulincer, M.

2016-01-01

This is the first study examining the association between victimization by bullying and attachment to both parents and teachers among students who report Learning Disorders (LD) and/or Attention Deficit Hyperactivity Disorder (ADHD). A total of 1,691 seventh- and eighth-grade students in six junior high schools completed questionnaires about…

Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

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Quednow, Boris B; Kometer, Michael; Geyer, Mark A; Vollenweider, Franz X

2012-01-01

The serotonin-2A receptor (5-HT2AR) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT2AR or 5-HT1AR agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT2A/2CR antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT2AR stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT2AR system. PMID:21956447

Attention Deficit Hyperactivity Disorder (ADHD)

Centers for Disease Control (CDC) Podcasts

2014-04-10

This podcast discusses Attention Deficit Hyperactivity Disorder, or ADHD, the most common behavioral disorder in children. Learn about symptoms, risk factors, and treatment.  Created: 4/10/2014 by National Center on Birth Defects and Developmental Disabilities (NCBDDD).   Date Released: 5/7/2014.

P2X7 Receptor Antagonism Attenuates the Intermittent Hypoxia-induced Spatial Deficits in a Murine Model of Sleep Apnea Via Inhibiting Neuroinflammation and Oxidative Stress.

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Deng, Yan; Guo, Xue-Ling; Yuan, Xiao; Shang, Jin; Zhu, Die; Liu, Hui-Guo

2015-08-20

The mechanism of the neural injury caused by chronic intermittent hypoxia (CIH) that characterizes obstructive sleep apnea syndrome (OSAS) is not clearly known. The purpose of this study was to investigate whether P2X7 receptor (P2X7R) is responsible for the CIH-induced neural injury and the possible pathway it involves. Eight-week-old male C57BL/6 mice were used. For each exposure time point, eight mice divided in room air (RA) and IH group were assigned to the study of P2X7R expression. Whereas in the 21 days-Brilliant Blue G (BBG, a selective P2X7R antagonist) study, 48 mice were randomly divided into CIH group, BBG-treated CIH group, RA group and BBG-treated RA group. The hippocampus P2X7R expression was determined by Western blotting and real-time polymerase chain reaction (PCR). The spatial learning was analyzed by Morris water maze. The nuclear factor kappa B (NFκB) and NADPH oxidase 2 (NOX2) expressions were analyzed by Western blotting. The expressions of tumor necrosis factor α, interleukin 1β (IL-β), IL-18, and IL-6 were measured by real-time PCR. The malondialdehyde and superoxide dismutase levels were detected by colorimetric method. Cell damage was evaluated by Hematoxylin and Eosin staining and Terminal Transferase dUTP Nick-end Labeling method. The P2X7R mRNA was elevated and sustained after 3-day IH exposure and the P2X7R protein was elevated and sustained after 7-day IH exposure. In the BBG study, the CIH mice showed severer neuronal cell damage and poorer performance in the behavior test. The increased NFκB and NOX2 expressions along with the inflammation injury and oxidative stress were also observed in the CIH group. BBG alleviated CIH-induced neural injury and consequent functional deficits. The P2X7R antagonism attenuates the CIH-induced neuroinflammation, oxidative stress, and spatial deficits, demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.

MK-801-induced deficits in social recognition in rats: reversal by aripiprazole, but not olanzapine, risperidone, or cannabidiol.

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Deiana, Serena; Watanabe, Akihito; Yamasaki, Yuki; Amada, Naoki; Kikuchi, Tetsuro; Stott, Colin; Riedel, Gernot

2015-12-01

Deficiencies in social activities are hallmarks of numerous brain disorders. With respect to schizophrenia, social withdrawal belongs to the category of negative symptoms and is associated with deficits in the cognitive domain. Here, we used the N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801) for induction of social withdrawal in rats and assessed the efficacy of several atypical antipsychotics with different pharmacological profiles as putative treatment. In addition, we reasoned that the marijuana constituent cannabidiol (CBD) may provide benefit or could be proposed as an adjunct treatment in combination with antipsychotics. Hooded Lister rats were tested in the three-chamber version for social interaction, with an initial novelty phase, followed after 3 min by a short-term recognition memory phase. No drug treatment affected sociability. However, distinct effects on social recognition were revealed. MK-801 reduced social recognition memory at all doses (>0.03 mg/kg). Predosing with aripiprazole dose-dependently (2 or 10 mg/kg) prevented the memory decline, but doses of 0.1 mg/kg risperidone or 1 mg/kg olanzapine did not. Intriguingly, CBD impaired social recognition memory (12 and 30 mg/kg) but did not rescue the MK-801-induced deficits. When CBD was combined with protective doses of aripiprazole (CBD-aripiprazole at 12 :  or 5 : 2 mg/kg) the benefit of the antipsychotic was lost. At the same time, activity-related changes in behaviour were excluded as underlying reasons for these pharmacological effects. Collectively, the combined activity of aripiprazole on dopamine D2 and serotonin 5HT1A receptors appears to provide a significant advantage over risperidone and olanzapine with respect to the rescue of cognitive deficits reminiscent of schizophrenia. The differential pharmacological properties of CBD, which are seemingly beneficial in human patients, did not back-translate and rescue the MK-801-induced social memory deficit.

College students with dyslexia: persistent linguistic deficits and foreign language learning.

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Downey, D M; Snyder, L E; Hill, B

2000-01-01

The first of these two studies compared college students with dyslexia enrolled in modified Latin and Spanish classes and non-dyslexic students enrolled in regular foreign language classes on measures of foreign language aptitude, word decoding, spelling, phonological awareness and word repetition. The groups did not differ on age or grade point average. Analyses indicated that students with dyslexia performed significantly poorer on the foreign language aptitude measures as well as on both phonological tasks, reading and spelling. In the second study, students with learning disabilities who were enrolled in a modified Latin class were not significantly different from their peers in a regular Latin class on grade point average or on performance on a proficiency examination at the end of the second semester. The data suggest that while phonological processing deficits persist into adulthood, students with dyslexia are able to acquire appropriate skills and information to successfully complete the University's foreign language requirement in classes modified to meet their needs.

Learned helplessness: unique features and translational value of a cognitive depression model.

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Vollmayr, Barbara; Gass, Peter

2013-10-01

The concept of learned helplessness defines an escape or avoidance deficit after uncontrollable stress and is regarded as a depression-like coping deficit in aversive but avoidable situations. Based on a psychological construct, it ideally complements other stress-induced or genetic animal models for major depression. Because of excellent face, construct, and predictive validity, it has contributed to the elaboration of several pathophysiological concepts and has brought forward new treatment targets. Whereas learned helplessness can be modeled not only in a broad variety of mammals, but also in fish and Drosophila, we will focus here on the use of this model in rats and mice, which are today the most common species for preclinical in vivo research in psychiatry.

Are Auditory and Visual Processing Deficits Related to Developmental Dyslexia?

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Georgiou, George K.; Papadopoulos, Timothy C.; Zarouna, Elena; Parrila, Rauno

2012-01-01

The purpose of this study was to examine if children with dyslexia learning to read a consistent orthography (Greek) experience auditory and visual processing deficits and if these deficits are associated with phonological awareness, rapid naming speed and orthographic processing. We administered measures of general cognitive ability, phonological…

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

Implications of CI therapy for Visual Deficit Training

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Edward eTaub

2014-10-01

Full Text Available We address here the question of whether the techniques of CI therapy, a family of treatments that has been employed in the rehabilitation of movement and language after brain damage might apply to the rehabilitation of such visual deficits as unilateral spatial neglect and visual field deficits. CI therapy has been used successfully for the upper and lower extremities after chronic stroke, cerebral palsy (CP, multiple sclerosis (MS, other CNS degenerative conditions, resection of motor areas of the brain, focal hand dystonia, and aphasia. Treatments making use of similar methods have proven efficacious for amblyopia.The CI therapy approach consists of four major components: intensive training, training by shaping, a transfer package to facilitate the transfer of gains from the treatment setting to everyday activities, and strong discouragement of compensatory strategies.CI therapy is said to be effective because it overcomes learned nonuse, a learned inhibition of movement that follows injury to the CNS. In addition, CI therapy produces substantial increases in the grey matter of motor areas on both sides of the brain. We propose here that these mechanisms are examples of more general processes: learned nonuse being considered parallel to sensory nonuse following damage to sensory areas of the brain, with both having in common diminished neural connections (DNC in the nervous system as an underlying mechanism. CI therapy would achieve its therapeutic effect by strengthening the diminished neural connections. Use-dependent cortical reorganization is considered to be an example of the more general neuroplastic mechanism of brain structure repurposing (BSR. If the mechanisms involved in these broader categories are involved in each of the deficits being considered, then it may be the principles underlying efficacious treatment in each case may be similar. The lessons learned during CI therapy research might then prove useful for the treatment of

Differentiating Children with Attention-Deficit/Hyperactivity Disorder, Conduct Disorder, Learning Disabilities and Autistic Spectrum Disorders by Means of Their Motor Behavior Characteristics

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Efstratopoulou, Maria; Janssen, Rianne; Simons, Johan

2012-01-01

The study was designed to investigate the discriminant validity of the Motor Behavior Checklist (MBC) for distinguishing four group of children independently classified with Attention-Deficit/Hyperactivity Disorder, (ADHD; N = 22), Conduct Disorder (CD; N = 17), Learning Disabilities (LD; N = 24) and Autistic Spectrum Disorders (ASD; N = 20).…

Potential Ameliorative Effects of Qing Ye Dan Against Cadmium Induced Prostatic Deficits via Regulating Nrf-2/HO-1 and TGF-β1/Smad Pathways.

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Du, Lifen; Lei, Yongfang; Chen, Jinglou; Song, Hongping; Wu, Xinying

2017-01-01

Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/ oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status. The prostatic inflammation was estimated by testing the levels of pro-inflammatory cytokines. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, fibronectin, vimentin and α-smooth muscle actin were measured by qPCR analysis. Additionally, the prostatic expressions of transforming growth factor-β1 (TGF-β1), type I TGF-β receptor (TGF-βRI), Smad2, phosphorylation-Smad2 (p-Smad2), Smad3, p-Smad3, Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot assay. It was found that QYD ameliorated the Cd-induced prostatic oxidative stress and inflammation, attenuated prostatic EMT, inhibited the TGF-β1/Smad pathway, increased Bcl-2/Bax ratio and enhanced the activity of Nrf-2/HO-1 pathway. These results showed that QYD could ameliorate Cd-induced prostatic deficits via modulating Nrf-2/HO-1 and TGF-β1/Smad pathways. © 2017 The Author(s). Published by S. Karger AG, Basel.

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.

Maternal chewing during prenatal stress ameliorates stress-induced hypomyelination, synaptic alterations, and learning impairment in mouse offspring.

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Suzuki, Ayumi; Iinuma, Mitsuo; Hayashi, Sakurako; Sato, Yuichi; Azuma, Kagaku; Kubo, Kin-Ya

2016-11-15

Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring. Copyright © 2016 Elsevier B.V. All rights reserved.

Depression and helplessness-induced cognitive deficits in the aged.

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Kennelly, K J; Hayslip, B; Richardson, S K

1985-01-01

Sixty-six community-residing elderly (mean age = 72.5) were categorized as depressed (mean = 11.3) or nondepressed (mean = 3.9) based on Beck Depression Inventory scores. After a pre-test battery measuring short-term memory and crystallized/fluid intelligence, the subjects responded to a word association task, disguised as a test of interpersonal empathy, under response dependent or response independent reinforcement conditions, or were assigned to a no treatment control. A post-test battery of alternate forms followed. Four of seven measures showed significant pre- to post-test declines in performance. For two of these four, response dependent reinforcement prevented otherwise significant declines. With pre-test differences statistically controlled, depression produced significant post-test deficits in three measures. Response dependent reinforcement eliminated this depression deficit in one measure. The results indicate that depression may exacerbate fatigue effects for the elderly and response dependent reinforcement may prevent fatigue-caused deficits in short-term memory.

South African Teachers' Attitudes toward Learners with Barriers to Learning: Attention-Deficit and Hyperactivity Disorder and Little or No Functional Speech

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Bornman, Juan; Donohue, Dana K.

2013-01-01

This study examined teachers' attitudes toward learners with two types of barriers to learning: a learner with attention-deficit and hyperactivity disorder (ADHD), and a learner with little or no functional speech (LNFS). The results indicated that although teachers reported that the learner with ADHD would be more disruptive in class and have a…

β-Adrenoceptor Blockade in the Basolateral Amygdala, But Not the Medial Prefrontal Cortex, Rescues the Immediate Extinction Deficit.

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Giustino, Thomas F; Seemann, Jocelyn R; Acca, Gillian M; Goode, Travis D; Fitzgerald, Paul J; Maren, Stephen

2017-12-01

Early psychological interventions, such as exposure therapy, rely on extinction learning to reduce the development of stress- and trauma-related disorders. However, recent research suggests that extinction often fails to reduce fear when administered soon after trauma. This immediate extinction deficit (IED) may be due to stress-induced dysregulation of neural circuits involved in extinction learning. We have shown that systemic β-adrenoceptor blockade with propranolol rescues the IED, but impairs delayed extinction. Here we sought to determine the neural locus of these effects. Rats underwent auditory fear conditioning and then received either immediate (30 min) or delayed (24 h) extinction training. We used bilateral intracranial infusions of propranolol into either the infralimbic division of the medial prefrontal cortex (mPFC) or the basolateral amygdala (BLA) to examine the effects of β-adrenoceptor blockade on immediate and delayed extinction learning. Interestingly, intra-BLA, but not intra-mPFC, propranolol rescued the IED; animals receiving intra-BLA propranolol prior to immediate extinction showed less spontaneous recovery of fear during extinction retrieval. Importantly, this was not due to impaired consolidation of the conditioning memory. In contrast, neither intra-BLA nor intra-mPFC propranolol affected delayed extinction learning. Overall, these data contribute to a growing literature suggesting dissociable roles for key nodes in the fear extinction circuit depending on the timing of extinction relative to conditioning. These data also suggest that heightened noradrenergic activity in the BLA underlies stress-induced extinction deficits. Propranolol may be a useful adjunct to behavioral therapeutic interventions in recently traumatized individuals who are at risk for developing trauma-related disorders.

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.

Prenatal choline supplementation attenuates MK-801-induced deficits in memory, motor function, and hippocampal plasticity in adult male rats.

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Nickerson, Chelsea A; Brown, Alexandra L; Yu, Waylin; Chun, Yoona; Glenn, Melissa J

2017-10-11

Choline is essential to the development and function of the central nervous system and supplemental choline during development is neuroprotective against a variety of insults, including neurotoxins like dizocilpine (MK-801). MK-801 is an NMDA receptor antagonist that is frequently used in rodent models of psychological disorders, particularly schizophrenia. At low doses, it causes cognitive impairments, and at higher doses it induces motor deficits, anhedonia, and neuronal degeneration. The primary goals of the present study were to investigate whether prenatal choline supplementation protects against the cognitive impairments, motor deficits, and neuropathologies that are precipitated by MK-801 administration in adulthood. Adult male Sprague-Dawley rats were fed a standard or supplemented choline diet prenatally. Using the novelty preference test of object recognition, we found that only prenatal standard-fed rats displayed memory consolidation deficits induced by low-dose MK-801 administered immediately following study of sample objects; all other groups, including prenatal choline supplemented rats given MK-801, showed intact memory. Following high-dose MK-801, prenatal choline supplementation significantly alleviated rats' motor response to MK-801, particularly ataxia. Using doublecortin and Ki67 to mark neurogenesis and cell division, respectively, in the hippocampus, we found that prenatal choline supplementation, in the face of MK-801 toxicity, protected against reduced hippocampal plasticity. Taken together, the current findings suggest that prenatal choline supplementation protects against a variety of behavioral and neural pathologies induced by the neurotoxin, MK-801. This research contributes to the growing body of evidence supporting the robust neuroprotective capacity of choline. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Acetylcholinesterase inhibition ameliorates deficits in motivational drive

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Martinowich Keri

2012-03-01

Full Text Available Abstract Background Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes. Methods We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes. Results CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens. Conclusions Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.

Glucocorticoid receptors and extinction retention deficits in the single prolonged stress model.

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Knox, D; Nault, T; Henderson, C; Liberzon, I

2012-10-25

Single prolonged stress (SPS) is a rodent model of post traumatic stress disorder that is comprised of serial application of restraint (r), forced swim (fs), and ether (eth) followed by a 7-day quiescent period. SPS induces extinction retention deficits and it is believed that these deficits are caused by the combined stressful effect of serial exposure to r, fs, and eth. However, this hypothesis remains untested. Neurobiological mechanisms by which SPS induces extinction retention deficits are unknown, but SPS enhances glucocorticoid receptor (GR) expression in the hippocampus, which is critical for contextual modulation of extinction retrieval. Upregulation of GRs in extinction circuits may be a mechanism by which SPS induces extinction retention deficits, but this hypothesis has not been examined. In this study, we systematically altered the stressors that constitute SPS (i.e. r, fs, eth), generating a number of partial SPS (p-SPS) groups, and observed the effects SPS and p-SPSs had on extinction retention and GR levels in the hippocampus and prefrontal cortex (PFC). PFC GRs were assayed, because regions of the PFC are critical for maintaining extinction. We predicted that only exposure to full SPS would result in extinction retention deficits and enhance hippocampal and PFC GR levels. Only exposure to full SPS induced extinction retention deficits. Hippocampal and PFC GR expression was enhanced by SPS and most p-SPSs, however hippocampal GR expression was significantly larger following the full SPS exposure than all other conditions. Our findings suggest that the combined stressful effect of serial exposure to r, fs, and eth results in extinction retention deficits. The results also suggest that simple enhancements in GR expression in the hippocampus and PFC are insufficient to result in extinction retention deficits, but raise the possibility that a threshold-enhancement in hippocampal GR expression contributes to SPS-induced extinction retention deficits

Psilocybin-induced deficits in automatic and controlled inhibition are attenuated by ketanserin in healthy human volunteers.

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Quednow, Boris B; Kometer, Michael; Geyer, Mark A; Vollenweider, Franz X

2012-02-01

The serotonin-2A receptor (5-HT(2A)R) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT(2A)R or 5-HT(1A)R agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT(2A/2C)R antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT(2A)R stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT(2A)R system.

Theory of Planned Behavior Predicts Graduation Intentions of Canadian and Israeli Postsecondary Students with and without Learning Disabilities/Attention Deficit Hyperactivity Disorder

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Fichten, Catherine S.; Heiman, Tali; Jorgensen, Mary; Nguyen, Mai Nhu; Havel, Alice; King, Laura; Budd, Jillian; Amsel, Rhonda

2016-01-01

We tested the ability of Ajzen's Theory of Planned Behavior (TPB) model to predict intention to graduate among Canadian and Israeli students with and without a learning disability/attention deficit hyperactivity disorder (LD/ADHD). Results based on 1486 postsecondary students show that the model's predictors (i.e., attitude, subjective norms,…

α-Asarone Attenuates Cognitive Deficit in a Pilocarpine-Induced Status Epilepticus Rat Model via a Decrease in the Nuclear Factor-κB Activation and Reduction in Microglia Neuroinflammation

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Hui-juan Liu

2017-12-01

Full Text Available BackgroundTemporal lobe epilepsy (TLE is one of the most drug-resistant types of epilepsy with about 80% of TLE patients falling into this category. Increasing evidence suggests that neuroinflammation, which has a critical role in the epileptogenesis of TLE, is associated with microglial activation. Therefore, agents that act toward the alleviation in microglial activation and the attenuation of neuroinflammation are promising candidates to treat TLE. α-Asarone is a major active ingredient of the Acori Graminei Rhizoma used in Traditional Chinese Medicine, which has been used to improve various disease conditions including stroke and convulsions. In addition, an increasing number of studies suggested that α-asarone can attenuate microglia-mediated neuroinflammation. Thus, we hypothesized that α-asarone is a promising neuroprotective agent for the treatment of the TLE.MethodsThe present study evaluated the therapeutic effects of α-asarone on microglia-mediated neuroinflammation and neuroprotection in vitro and in vivo, using an untreated control group, a status epilepticus (SE-induced group, and an SE-induced α-asarone pretreated group. A pilocarpine-induced rat model of TLE was established to investigate the neuroprotective effects of α-asarone in vivo. For the in vitro study, lipopolysaccharide (LPS-stimulated primary cultured microglial cells were used.ResultsThe results indicated that the brain microglial activation in the rats of the SE rat model led to important learning and memory deficit. Preventive treatment with α-asarone restrained microglial activation and reduced learning and memory deficit. In the in vitro studies, α-asarone significantly suppressed proinflammatory cytokine production in primary cultured microglial cells and attenuated the LPS-stimulated neuroinflammatory responses. Our mechanistic study revealed that α-asarone inhibited inflammatory processes by regulation the transcription levels of kappa-B, by blocking

Chronic epigallocatechin-3-gallate ameliorates learning and memory deficits in diabetic rats via modulation of nitric oxide and oxidative stress.

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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.

Routine post-weaning handling of rats prevents isolation rearing-induced deficit in prepulse inhibition

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M.L.N.M. Rosa

2005-11-01

Full Text Available Rats reared under isolation conditions from weaning present a number of behavioral changes compared to animals reared under social conditions (group housing. These changes include deficits in prepulse inhibition (PPI of the startle reflex to a loud sound. PPI refers to the reduction of the magnitude of the startle reflex when a relatively weak stimulus (the prepulse precedes by an appropriate time interval the intense startle-elicing stimulus (the pulse. PPI is useful for studying sensorimotor integration. The present study evaluated the effect of handling on the impairment of PPI induced by isolation-rearing. Male Wistar rats (N = 11-15/group were housed in groups (5 per cage and handled three times a week or isolated (housed individually since weaning (21 days for 10 weeks when they reach approximately 150 g. The isolated rats were divided into "minimally handled" animals (handled once a week for cleaning purposes only or "handled" animals (handled three times a week. This handling consisted of grasping the rat by the tail and moving it to a clean cage (approximately 5 s. A statistically significant reduction (52% in the PPI test was found only in the isolated group with minimal handling while no difference was seen between grouped animals and isolated handled animals. These results indicate that isolation rearing causes disruption in the PPI at adult age, which serves as an index of attention deficit. This change in the sensory processing of information induced by post-weaning isolation can be prevented by handling during the development of the animal.

Routine post-weaning handling of rats prevents isolation rearing-induced deficit in prepulse inhibition.

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Rosa, M L N M; Silva, R C B; Moura-de-Carvalho, F T; Brandão, M L; Guimarães, F S; Del Bel, E A

2005-11-01

Rats reared under isolation conditions from weaning present a number of behavioral changes compared to animals reared under social conditions (group housing). These changes include deficits in prepulse inhibition (PPI) of the startle reflex to a loud sound. PPI refers to the reduction of the magnitude of the startle reflex when a relatively weak stimulus (the prepulse) precedes by an appropriate time interval the intense startle-elicing stimulus (the pulse). PPI is useful for studying sensorimotor integration. The present study evaluated the effect of handling on the impairment of PPI induced by isolation-rearing. Male Wistar rats (N = 11-15/group) were housed in groups (5 per cage and handled three times a week) or isolated (housed individually) since weaning (21 days) for 10 weeks when they reach approximately 150 g. The isolated rats were divided into "minimally handled" animals (handled once a week for cleaning purposes only) or "handled" animals (handled three times a week). This handling consisted of grasping the rat by the tail and moving it to a clean cage (approximately 5 s). A statistically significant reduction (52%) in the PPI test was found only in the isolated group with minimal handling while no difference was seen between grouped animals and isolated handled animals. These results indicate that isolation rearing causes disruption in the PPI at adult age, which serves as an index of attention deficit. This change in the sensory processing of information induced by post-weaning isolation can be prevented by handling during the development of the animal.

Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone beta1 receptor gene.

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McDonald, M P; Wong, R; Goldstein, G; Weintraub, B; Cheng, S Y; Crawley, J N

1998-01-01

Resistance to thyroid hormone (RTH) is a human syndrome mapped to the thyroid receptor beta (TRbeta) gene on chromosome 3, representing a mutation of the ligand-binding domain of the TRbeta gene. The syndrome is characterized by reduced tissue responsiveness to thyroid hormone and elevated serum levels of thyroid hormones. A common behavioral phenotype associated with RTH is attention deficit hyperactivity disorder (ADHD). To test the hypothesis that RTH produces attention deficits and/or hyperactivity, transgenic mice expressing a mutant TRbeta gene were generated. The present experiment tested RTH transgenic mice from the PV kindred on behavioral tasks relevant to the primary features of ADHD: hyperactivity, sustained attention (vigilance), learning, and impulsivity. Male transgenic mice showed elevated locomotor activity in an open field compared to male wild-type littermate controls. Both male and female transgenic mice exhibited impaired learning of an autoshaping task, compared to wild-type controls. On a vigilance task in an operant chamber, there were no differences between transgenics and controls on the proportion of hits, response latency, or duration of stimulus tolerated. On an operant go/no-go task measuring sustained attention and impulsivity, there were no differences between controls and transgenics. These results indicate that transgenic mice bearing a mutant human TRbeta gene demonstrate several behavioral characteristics of ADHD and may serve a valuable heuristic role in elucidating possible candidate genes in converging pathways for other causes of ADHD.

Hyperactivity and Learning Deficits in Transgenic Mice Bearing a Human Mutant Thyroid Hormone β1 Receptor Gene

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McDonald, Michael P.; Wong, Rosemary; Goldstein, Gregory; Weintraub, Bruce; Cheng, Sheue-yann; Crawley, Jacqueline N.

1998-01-01

Resistance to thyroid hormone (RTH) is a human syndrome mapped to the thyroid receptor β (TRβ) gene on chromosome 3, representing a mutation of the ligandbinding domain of the TRβ gene. The syndrome is characterized by reduced tissue responsiveness to thyroid hormone and elevated serum levels of thyroid hormones. A common behavioral phenotype associated with RTH is attention deficit hyperactivity disorder (ADHD). To test the hypothesis that RTH produces attention deficits and/or hyperactivity, transgenic mice expressing a mutant TRβ gene were generated. The present experiment tested RTH transgenic mice from the PV kindred on behavioral tasks relevant to the primary features of ADHD: hyperactivity, sustained attention (vigilance), learning, and impulsivity. Male transgenic mice showed elevated locomotor activity in an open field compared to male wild-type littermate controls. Both male and female transgenic mice exhibited impaired learning of an autoshaping task, compared to wild-type controls. On a vigilance task in an operant chamber, there were no differences between transgenics and controls on the proportion of hits, response latency, or duration of stimulus tolerated. On an operant go/no-go task measuring sustained attention and impulsivity, there were no differences between controls and transgenics. These results indicate that transgenic mice bearing a mutant human TRβ gene demonstrate several behavioral characteristics of ADHD and may serve a valuable heuristic role in elucidating possible candidate genes in converging pathways for other causes of ADHD. PMID:10454355

Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory

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Zhao Li

2018-01-01

Full Text Available The chemotherapeutic agent paclitaxel is widely used for cancer treatment. Paclitaxel treatment impairs learning and memory function, a side effect that reduces the quality of life of cancer survivors. However, the neural mechanisms underlying paclitaxel-induced impairment of learning and memory remain unclear. Paclitaxel treatment leads to proinflammatory factor release and neuronal apoptosis. Thus, we hypothesized that paclitaxel impairs learning and memory function through proinflammatory factor-induced neuronal apoptosis. Neuronal apoptosis was assessed by TUNEL assay in the hippocampus. Protein expression levels of tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β in the hippocampus tissue were analyzed by Western blot assay. Spatial learning and memory function were determined by using the Morris water maze (MWM test. Paclitaxel treatment significantly increased the escape latencies and decreased the number of crossing in the MWM test. Furthermore, paclitaxel significantly increased the number of TUNEL-positive neurons in the hippocampus. Also, paclitaxel treatment increased the expression levels of TNF-α and IL-1β in the hippocampus tissue. In addition, the TNF-α synthesis inhibitor thalidomide significantly attenuated the number of paclitaxel-induced TUNEL-positive neurons in the hippocampus and restored the impaired spatial learning and memory function in paclitaxel-treated rats. These data suggest that TNF-α is critically involved in the paclitaxel-induced impairment of learning and memory function.

S61. THE ASSOCIATION OF VERBAL LEARNING DEFICITS WITH AGE AND SYMPTOMS IN SCHIZOPHRENIA

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Kontis, Dimitrios; Giannakopoulou, Alexandra; Theochari, Eirini; Andreopoulou, Angeliki; Vassilouli, Spyridoula; Giannakopoulou, Dimitra; Siettou, Eleni; Tsaltas, Eleftheria

2018-01-01

delayed recall. Discussion Age and symptoms are associated with immediate verbal learning and memory impairments but not with deficits in verbal delayed recall in schizophrenia. The effects of medication remain to be explored in future analyses. Cognitive remediation programmes against verbal learning deficits in individuals with schizophrenia should take into account their age as well as their symptomatology.

CHILDREN’S GIFTEDNESS AND ASSOCIATED PROBLEMS. THE TWICE EXCEPTIONALITY PHENOMENON. GIFTEDNESS AND LEARNING PROBLEMS. GIFTEDNESS AND ATTENTION DEFICIT/ HYPERACTIVITY DISORDER (А REVIEW OF LITERATURE

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O. A. Pylaeva

2015-01-01

Full Text Available In accordance with current views, giftedness are considered as the systemic psychic property developing throughout a lifetime, which determines the human possibility of achieving higher (unusual, outstanding results in one or several kinds of activities as compared to other people. People who are endowed with extraordinary abilities may be infrequently called absolutely somatically and mentally healthy. There are data that giftedness in childhood are frequently concurrent with both somatic diseases and different neurological disorders. Many gifted children are diagnosed as having left-handedness, speech disorders, and autoimmune diseases. There are scientific works on the association of giftedness with neurological and psychiatric disorders, including attention deficit/hyperactivity disorder (ADHD, learning problems (dyslexia in particular, autism (including Asperger’s syndrome, bipolar disorder, and migraine. According to the available data, approximately 3–5 % of children fall into a category of intellectually gifted ones; some children (2–5 to 20 % or more of all gifted children according to different findings may have learning problems. The terms “twice-gifted” or “twice-exceptional” are proposed to characterize children with giftedness concurrent with learning problems, attention deficit (including ADHD, or other impairments of cognitive functions and behavior (including oppositional disorder and obsessive-compulsive disorder. These children need the more attention of teachers and other correction approaches and adaptation methods to be elaborated as compared to the procedures used for gifted children, on the one hand, and for those with learning problems, behavioral and attention disorders, on the other hand. There is a need for the development and further strengthening of strong suits (gift and correction, adaptation of deficits in children with “twice exceptionality”. The review presents the history of studying the �

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

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Nielsen, Trine Damgaard; Larsen, Dorrit Bjerg; Hansen, Suzanne Lisbet

2010-01-01

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...

Delayed growth, motor function and learning in preterm pigs during early postnatal life

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Andersen, Anders D.; Sangild, Per T.; Munch, Sara L.

2016-01-01

Preterm birth interrupts normal fetal growth with consequences for postnatal growth and organ development. In preterm infants, many physiological deficits adapt and disappear with advancing postnatal age, but some may persist into childhood. We hypothesized that preterm birth would induce impaired......, and learning, relative to term pigs (all P

Activation of the canonical nuclear factor-κB pathway is involved in isoflurane-induced hippocampal interleukin-1β elevation and the resultant cognitive deficits in aged rats

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Li, Zheng-Qian; Rong, Xiao-Ying; Liu, Ya-Jie; Ni, Cheng; Tian, Xiao-Sheng; Mo, Na; Chui, De-Hua; Guo, Xiang-Yang

2013-01-01

Highlights: •Isoflurane induces hippocampal IL-1β elevation and cognitive deficits in aged rats. •Isoflurane transiently activates the canonical NF-κB pathway in aged rat hippocampus. •NF-κB inhibitor mitigates isoflurane-induced IL-1β elevation and cognitive deficits. •We report a linkage between NF-κB signaling, IL-1β expression, and cognitive changes. -- Abstract: Although much recent evidence has demonstrated that neuroinflammation contributes to volatile anesthetic-induced cognitive deficits, there are few existing mechanistic explanations for this inflammatory process. This study was conducted to investigate the effects of the volatile anesthetic isoflurane on canonical nuclear factor (NF)-κB signaling, and to explore its association with hippocampal interleukin (IL)-1β levels and anesthetic-related cognitive changes in aged rats. After a 4-h exposure to 1.5% isoflurane in 20-month-old rats, increases in IκB kinase and IκB phosphorylation, as well as a reduction in the NF-κB inhibitory protein (IκBα), were observed in the hippocampi of isoflurane-exposed rats compared with control rats. These events were accompanied by an increase in NF-κB p65 nuclear translocation at 6 h after isoflurane exposure and hippocampal IL-1β elevation from 1 to 6 h after isoflurane exposure. Nevertheless, no significant neuroglia activation was observed. Pharmacological inhibition of NF-κB activation by pyrrolidine dithiocarbamate markedly suppressed the IL-1β increase and NF-κB signaling, and also mitigated the severity of cognitive deficits in the Morris water maze task. Overall, our results demonstrate that isoflurane-induced cognitive deficits may stem from upregulation of hippocampal IL-1β, partially via activation of the canonical NF-κB pathway, in aged rats

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

Therapeutic Effects of Extinction Learning as a Model of Exposure Therapy in Rats

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Fucich, Elizabeth A; Paredes, Denisse; Morilak, David A

2016-01-01

Current treatments for stress-related psychiatric disorders, such as depression and posttraumatic stress disorder (PTSD), are inadequate. Cognitive behavioral psychotherapies, including exposure therapy, are an alternative to pharmacotherapy, but the neurobiological mechanisms are unknown. Preclinical models demonstrating therapeutic effects of behavioral interventions are required to investigate such mechanisms. Exposure therapy bears similarity to extinction learning. Thus, we investigated the therapeutic effects of extinction learning as a behavioral intervention to model exposure therapy in rats, testing its effectiveness in reversing chronic stress-induced deficits in cognitive flexibility and coping behavior that resemble dimensions of depression and PTSD. Rats were fear-conditioned by pairing a tone with footshock, and then exposed to chronic unpredictable stress (CUS) that induces deficits in cognitive set-shifting and active coping behavior. They then received an extinction learning session as a therapeutic intervention by repeated exposure to the tone with no shock. Effects on cognitive flexibility and coping behavior were assessed 24 h later on the attentional set-shifting test or shock-probe defensive burying test, respectively. Extinction reversed the CUS-induced deficits in cognitive flexibility and coping behavior, and increased phosphorylation of ribosomal protein S6 in the medial prefrontal cortex (mPFC) of stress-compromised rats, suggesting a role for activity-dependent protein synthesis in the therapeutic effect. Inhibiting protein synthesis by microinjecting anisomycin into mPFC blocked the therapeutic effect of extinction on cognitive flexibility. These results demonstrate the utility of extinction as a model by which to study mechanisms underlying exposure therapy, and suggest these mechanisms involve protein synthesis in the mPFC, the further study of which may identify novel therapeutic targets. PMID:27417516

ATTENTION DEFICIT/HYPERACTIVITY DISORDER (ADHD)

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Enrique

People who suffer from ADHD are far more likely than normal to drop out of school (32 ... secondary to learning disabilities, partial sensory deficits or even low cognitive ... bad days (Fig. 3), which can lead to frustration for teachers, parents and the child, as there is always the feeling that ... boys who often present very young.

Dietary Intake of Sulforaphane-Rich Broccoli Sprout Extracts during Juvenile and Adolescence Can Prevent Phencyclidine-Induced Cognitive Deficits at Adulthood.

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Yumi Shirai

Full Text Available Oxidative stress and inflammation play a role in cognitive impairment, which is a core symptom of schizophrenia. Furthermore, a hallmark of the pathophysiology of this disease is the dysfunction of cortical inhibitory γ-aminobutyric acid (GABA neurons expressing parvalbumin (PV, which is also involved in cognitive impairment. Sulforaphane (SFN, an isothiocyanate derived from broccoli, is a potent activator of the transcription factor Nrf2, which plays a central role in the inducible expressions of many cytoprotective genes in response to oxidative stress. Keap1 is a cytoplasmic protein that is essential for the regulation of Nrf2 activity. Here, we found that pretreatment with SFN attenuated cognitive deficits, the increase in 8-oxo-dG-positive cells, and the decrease in PV-positive cells in the medial prefrontal cortex and hippocampus after repeated administration of phencyclidine (PCP. Furthermore, PCP-induced cognitive deficits were improved by the subsequent subchronic administration of SFN. Interestingly, the dietary intake of glucoraphanin (a glucosinolate precursor of SFN during the juvenile and adolescence prevented the onset of PCP-induced cognitive deficits as well as the increase in 8-oxo-dG-positive cells and the decrease in PV-positive cells in the brain at adulthood. Moreover, the NRF2 gene and the KEAP1 gene had an epistatic effect on cognitive impairment (e.g., working memory and processing speed in patients with schizophrenia. These findings suggest that SFN may have prophylactic and therapeutic effects on cognitive impairment in schizophrenia. Therefore, the dietary intake of SFN-rich broccoli sprouts during the juvenile and adolescence may prevent the onset of psychosis at adulthood.

Environmental enrichment and exercise are better than social enrichment to reduce memory deficits in amyloid beta neurotoxicity.

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Prado Lima, Mariza G; Schimidt, Helen L; Garcia, Alexandre; Daré, Letícia R; Carpes, Felipe P; Izquierdo, Ivan; Mello-Carpes, Pâmela B

2018-03-06

Recently, nongenetic animal models to study the onset and development of Alzheimer's disease (AD) have appeared, such as the intrahippocampal infusion of peptides present in Alzheimer amyloid plaques [i.e., amyloid-β (Aβ)]. Nonpharmacological approaches to AD treatment also have been advanced recently, which involve combinations of behavioral interventions whose specific effects are often difficult to determine. Here we isolate the neuroprotective effects of three of these interventions-environmental enrichment (EE), anaerobic physical exercise (AnPE), and social enrichment (SE)-on Aβ-induced oxidative stress and on impairments in learning and memory induced by Aβ. Wistar rats were submitted to 8 wk of EE, AnPE, or SE, followed by Aβ infusion in the dorsal hippocampus. Short-term memory (STM) and long-term memory (LTM) of object recognition (OR) and social recognition (SR) were evaluated. Biochemical assays determined hippocampal oxidative status: reactive oxygen species, lipid peroxidation by thiobarbituric acid reactive substance (TBARS) test, and total antioxidant capacity by ferric reducing/antioxidant power (FRAP), as well as acetylcholinesterase activity. Aβ infusion resulted in memory deficits and hippocampal oxidative damage. EE and AnPE prevented all memory deficits (STM and LTM of OR and SR) and lipid peroxidation (i.e., TBARS). SE prevented only the SR memory deficits and the decrease of total antioxidant capacity decrease (i.e., FRAP). Traditionally, findings obtained with EE protocols do not allow discrimination of the roles of the three individual factors involved. Here we demonstrate that EE and physical exercise have better neuroprotective effects than SE in memory deficits related to Aβ neurotoxicity in the AD model tested.

Social modulation of stress reactivity and learning in young worker honey bees.

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Elodie Urlacher

Full Text Available Alarm pheromone and its major component isopentylacetate induce stress-like responses in forager honey bees, impairing their ability to associate odors with a food reward. We investigated whether isopentylacetate exposure decreases appetitive learning also in young worker bees. While isopentylacetate-induced learning deficits were observed in guards and foragers collected from a queen-right colony, learning impairments resulting from exposure to this pheromone could not be detected in bees cleaning cells. As cell cleaners are generally among the youngest workers in the colony, effects of isopentylacetate on learning behavior were examined further using bees of known age. Adult workers were maintained under laboratory conditions from the time of adult emergence. Fifty percent of the bees were exposed to queen mandibular pheromone during this period, whereas control bees were not exposed to this pheromone. Isopentylacetate-induced learning impairments were apparent in young (less than one week old controls, but not in bees of the same age exposed to queen mandibular pheromone. This study reveals young worker bees can exhibit a stress-like response to alarm pheromone, but isopentylacetate-induced learning impairments in young bees are suppressed by queen mandibular pheromone. While isopentylacetate exposure reduced responses during associative learning (acquisition, it did not affect one-hour memory retrieval.

Social Modulation of Stress Reactivity and Learning in Young Worker Honey Bees

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Mercer, Alison R.

2014-01-01

Alarm pheromone and its major component isopentylacetate induce stress-like responses in forager honey bees, impairing their ability to associate odors with a food reward. We investigated whether isopentylacetate exposure decreases appetitive learning also in young worker bees. While isopentylacetate-induced learning deficits were observed in guards and foragers collected from a queen-right colony, learning impairments resulting from exposure to this pheromone could not be detected in bees cleaning cells. As cell cleaners are generally among the youngest workers in the colony, effects of isopentylacetate on learning behavior were examined further using bees of known age. Adult workers were maintained under laboratory conditions from the time of adult emergence. Fifty percent of the bees were exposed to queen mandibular pheromone during this period, whereas control bees were not exposed to this pheromone. Isopentylacetate-induced learning impairments were apparent in young (less than one week old) controls, but not in bees of the same age exposed to queen mandibular pheromone. This study reveals young worker bees can exhibit a stress-like response to alarm pheromone, but isopentylacetate-induced learning impairments in young bees are suppressed by queen mandibular pheromone. While isopentylacetate exposure reduced responses during associative learning (acquisition), it did not affect one-hour memory retrieval. PMID:25470128

Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine.

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Ahn, Kyung-Heup; Sewell, Andrew; Elander, Jacqueline; Pittman, Brian; Ranganathan, Mohini; Gunduz-Bruce, Handan; Krystal, John; D'Souza, Deepak Cyril

2015-11-01

Some schizophrenia patients are more sensitive to amphetamine (AMPH)-induced exacerbations in psychosis-an effect that correlates with higher striatal dopamine release. This enhanced vulnerability may be related to gamma-aminobutyric acid (GABA) deficits observed in schizophrenia. We hypothesized that a pharmacologically induced GABA deficit would create vulnerability to the psychotomimetic effects to the 'subthreshold' dose of AMPH in healthy subjects, which by itself would not induce clinically significant increase in positive symptoms. To test this hypothesis, a GABA deficit was induced by intravenous infusion of iomazenil (IOM; 3.7 μg/kg), an antagonist and partial inverse agonist of benzodiazepine receptor. A subthreshold dose of AMPH (0.1 mg/kg) was administered by intravenous infusion. Healthy subjects received placebo IOM followed by placebo AMPH, active IOM followed by placebo AMPH, placebo IOM followed by active AMPH, and active IOM followed by active AMPH in a randomized, double-blind crossover design over 4 test days. Twelve healthy subjects who had a subclinical response to active AMPH alone were included in the analysis. Psychotomimetic effects (Positive and Negative Syndrome Scale (PANSS)), perceptual alterations (Clinician Administered Dissociative Symptoms Scale (CADSS)), and subjective effects (visual analog scale) were captured before and after the administration of drugs. IOM significantly augmented AMPH-induced peak changes in PANSS positive symptom subscale and both subjective and objective CADSS scores. There were no pharmacokinetic interactions. In conclusion, GABA deficits increased vulnerability to amphetamine-induced psychosis-relevant effects in healthy subjects, suggesting that pre-existing GABA deficits may explain why a subgroup of schizophrenia patients are vulnerable to AMPH.

Decision-making deficits in patients with chronic schizophrenia: Iowa Gambling Task and Prospect Valence Learning model.

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Kim, Myung-Sun; Kang, Bit-Na; Lim, Jae Young

2016-01-01

Decision-making is the process of forming preferences for possible options, selecting and executing actions, and evaluating the outcome. This study used the Iowa Gambling Task (IGT) and the Prospect Valence Learning (PVL) model to investigate deficits in risk-reward related decision-making in patients with chronic schizophrenia, and to identify decision-making processes that contribute to poor IGT performance in these patients. Thirty-nine patients with schizophrenia and 31 healthy controls participated. Decision-making was measured by total net score, block net scores, and the total number of cards selected from each deck of the IGT. PVL parameters were estimated with the Markov chain Monte Carlo sampling scheme in OpenBugs and BRugs, its interface to R, and the estimated parameters were analyzed with the Mann-Whitney U-test. The schizophrenia group received significantly lower total net scores compared to the control group. In terms of block net scores, an interaction effect of group × block was observed. The block net scores of the schizophrenia group did not differ across the five blocks, whereas those of the control group increased as the blocks progressed. The schizophrenia group obtained significantly lower block net scores in the fourth and fifth blocks of the IGT and selected cards from deck D (advantageous) less frequently than the control group. Additionally, the schizophrenia group had significantly lower values on the utility-shape, loss-aversion, recency, and consistency parameters of the PVL model. These results indicate that patients with schizophrenia experience deficits in decision-making, possibly due to failure in learning the expected value of each deck, and incorporating outcome experiences of previous trials into expectancies about options in the present trial.

Inhibition of 5a-reductase in the nucleus accumbens counters sensorimotor gating deficits induced by dopaminergic activation

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Devoto, Paola; Frau, Roberto; Bini, Valentina; Pillolla, Giuliano; Saba, Pierluigi; Flore, Giovanna; Corona, Marta; Marrosu, Francesco; Bortolato, Marco

2012-01-01

Summary Cogent evidence highlights a key role of neurosteroids and androgens in schizophrenia. We recently reported that inhibition of steroid 5α-reductase (5αR), the rate-limiting enzyme in neurosteroid synthesis and androgen metabolism, elicits antipsychotic-like effects in humans and animal models, without inducing extrapyramidal side effects. To elucidate the anatomical substrates mediating these effects, we investigated the contribution of peripheral and neural structures to the behavioral effects of the 5αR inhibitor finasteride (FIN) on the prepulse inhibition (PPI) of the acoustic startle reflex (ASR), a rat paradigm that dependably simulates the sensorimotor gating impairments observed in schizophrenia and other neuropsychiatric disorders. The potential effect of drug-induced ASR modifications on PPI was excluded by measuring this index both as percent (%PPI) and absolute values (ΔPPI). In both orchidectomized and sham-operated rats, FIN prevented the %PPI deficits induced by the dopamine (DA) receptor agonists apomorphine (APO, 0.25 mg/kg, SC) and d-amphetamine (AMPH, 2.5 mg/kg, SC), although the latter effect was not corroborated by ΔPPI analysis. Conversely, APO-induced PPI deficits were countered by FIN infusions in the brain ventricles (10 μg/1 μl) and in the nucleus accumbens (NAc) shell and core (0.5 μg/0.5 μl/side). No significant PPI-ameliorating effect was observed following FIN injections in other brain regions, including dorsal caudate, basolateral amygdala, ventral hippocampus and medial prefrontal cortex, although a statistical trend was observed for the latter region. The efflux of DA in NAc was increased by systemic, but not intracerebral FIN administration. Taken together, these findings suggest that the role of 5αR in gating regulation is based on post-synaptic mechanisms in the NAc, and is not directly related to alterations in DA efflux in this region. PMID:22029952

Amyloid β-mediated Zn2+ influx into dentate granule cells transiently induces a short-term cognitive deficit.

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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.

Amyloid β-mediated Zn2+ influx into dentate granule cells transiently induces a short-term cognitive deficit.

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Takeda, Atsushi; Nakamura, Masatoshi; Fujii, Hiroaki; Uematsu, Chihiro; Minamino, Tatsuya; Adlard, Paul A; Bush, Ashley I; Tamano, Haruna

2014-01-01

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.

How Do Students with Attention-Deficit/Hyperactivity Disorders and Writing Learning Disabilities Differ from Their Nonlabeled Peers in the Ability to Compose Texts?

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Rodríguez, Celestino; Grünke, Matthias; González-Castro, Paloma; García, Trinidad; Álvarez-García, David

2015-01-01

This comparative study investigated the productivity and the process of written composition in students with and without disabilities between 8 and 16 years of age. Participants were assigned to four groups as follows: (a) 59 with both attention-deficit/hyperactivity disorders (ADHD) and writing learning disabilities (WLD), (b) 40 with ADHD, (c)…

Learning Disabilities and ADHD

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... of illnesses and disabilities Learning disabilities and ADHD Learning disabilities and ADHD Learning disabilities affect how you ... ADHD. Learning disabilities Attention deficit hyperactivity disorder (ADHD) Learning disabilities top Having a learning disability does not ...

Aloe vera gel improves behavioral deficits and oxidative status in streptozotocin-induced diabetic rats.

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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.

An Early Postnatal Oxytocin Treatment Prevents Social and Learning Deficits in Adult Mice Deficient for Magel2, a Gene Involved in Prader-Willi Syndrome and Autism.

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Meziane, Hamid; Schaller, Fabienne; Bauer, Sylvian; Villard, Claude; Matarazzo, Valery; Riet, Fabrice; Guillon, Gilles; Lafitte, Daniel; Desarmenien, Michel G; Tauber, Maithé; Muscatelli, Françoise

2015-07-15

Mutations of MAGEL2 have been reported in patients presenting with autism, and loss of MAGEL2 is also associated with Prader-Willi syndrome, a neurodevelopmental genetic disorder. This study aimed to determine the behavioral phenotype of Magel2-deficient adult mice, to characterize the central oxytocin (OT) system of these mutant mice, and to test the curative effect of a peripheral OT treatment just after birth. We assessed the social and cognitive behavior of Magel2-deficient mice, analyzed the OT system of mutant mice treated or not by a postnatal administration of OT, and determined the effect of this treatment on the brain. Magel2 inactivation induces a deficit in social recognition and social interaction and a reduced learning ability in adult male mice. In these mice, we reveal anatomical and functional modifications of the OT system and show that these defects change from birth to adulthood. Daily administration of OT in the first postnatal week was sufficient to prevent deficits in social behavior and learning abilities in adult mutant male mice. We show that this OT treatment partly restores a normal OT system. Thus, we report that an alteration of the OT system around birth has long-term consequences on behavior and on cognition. Importantly, an acute OT treatment of Magel2-deficient pups has a curative effect. Our study reveals that OT plays a crucial role in setting social behaviors during a period just after birth. An early OT treatment in this critical period could be a novel therapeutic approach for the treatment of neurodevelopmental disorders such as Prader-Willi syndrome and autism. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles.

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Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

2016-01-01

Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8-9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits.

Impairments in action-outcome learning in schizophrenia.

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Morris, Richard W; Cyrzon, Chad; Green, Melissa J; Le Pelley, Mike E; Balleine, Bernard W

2018-03-03

Learning the causal relation between actions and their outcomes (AO learning) is critical for goal-directed behavior when actions are guided by desire for the outcome. This can be contrasted with habits that are acquired by reinforcement and primed by prevailing stimuli, in which causal learning plays no part. Recently, we demonstrated that goal-directed actions are impaired in schizophrenia; however, whether this deficit exists alongside impairments in habit or reinforcement learning is unknown. The present study distinguished deficits in causal learning from reinforcement learning in schizophrenia. We tested people with schizophrenia (SZ, n = 25) and healthy adults (HA, n = 25) in a vending machine task. Participants learned two action-outcome contingencies (e.g., push left to get a chocolate M&M, push right to get a cracker), and they also learned one contingency was degraded by delivery of noncontingent outcomes (e.g., free M&Ms), as well as changes in value by outcome devaluation. Both groups learned the best action to obtain rewards; however, SZ did not distinguish the more causal action when one AO contingency was degraded. Moreover, action selection in SZ was insensitive to changes in outcome value unless feedback was provided, and this was related to the deficit in AO learning. The failure to encode the causal relation between action and outcome in schizophrenia occurred without any apparent deficit in reinforcement learning. This implies that poor goal-directed behavior in schizophrenia cannot be explained by a more primary deficit in reward learning such as insensitivity to reward value or reward prediction errors.

Crocin Improved Learning and Memory Impairments in Streptozotocin-Induced Diabetic Rats

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Esmaeal Tamaddonfard

2013-01-01

Full Text Available Objective(s: Crocin influences many biological functions including memory and learning. The present study was aimed to investigate the effects of crocin on learning and memory impairments in streptozotocine-induced diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (IP injection of streptozotocin (STZ, 45 mg/kg. Transfer latency (TL paradigm in elevated plus-maze (EPM was used as an index of learning and memory. Plasma levels of total antioxidant capacity (TAC and malondialdehyde (MDA, blood levels of glucose, and serum concentrations of insulin were measured. The number of hippocampal neurons was also counted. Results: STZ increased acquisition transfer latency (TL1 and retention transfer latency (TL2, and MDA, decreased transfer latency shortening (TLs and TCA, produced hyperglycemia and hypoinsulinemia, and reduced the number of neurons in the hippocampus. Learning and memory impairments and blood TCA, MDA, glucose, and insulin changes induced by streptozotocin were improved with long-term IP injection of crocin at doses of 15 and 30 mg/kg. Crocin prevented hippocampal neurons number loss in diabetic rats. Conclusion: The results indicate that oxidative stress, hyperglycemia, hypoinsulinemia, and reduction of hippocampal neurons may be involved in learning and memory impairments in STZ-induced diabetic rats. Antioxidant, antihyperglycemic, antihypoinsulinemic, and neuroprotective activities of crocin might be involved in improving learning and memory impairments.

Appetite and Energy Intake Responses to Acute Energy Deficits in Females versus Males

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ALAJMI, NAWAL; DEIGHTON, KEVIN; KING, JAMES A.; REISCHAK-OLIVEIRA, ALVARO; WASSE, LUCY K.; JONES, JENNY; BATTERHAM, RACHEL L.; STENSEL, DAVID J.

2016-01-01

ABSTRACT Purpose To explore whether compensatory responses to acute energy deficits induced by exercise or diet differ by sex. Methods In experiment one, 12 healthy women completed three 9-h trials (control, exercise-induced (Ex-Def) and food restriction–induced energy deficit (Food-Def)) with identical energy deficits being imposed in the Ex-Def (90-min run, ∼70% of V˙O2max) and Food-Def trials. In experiment two, 10 men and 10 women completed two 7-h trials (control and exercise). Sixty minutes of running (∼70% of V˙O2max) was performed at the beginning of the exercise trial. The participants rested throughout the remainder of the exercise trial and during the control trial. Appetite ratings, plasma concentrations of gut hormones, and ad libitum energy intake were assessed during main trials. Results In experiment one, an energy deficit of approximately 3500 kJ induced via food restriction increased appetite and food intake. These changes corresponded with heightened concentrations of plasma acylated ghrelin and lower peptide YY3–36. None of these compensatory responses were apparent when an equivalent energy deficit was induced by exercise. In experiment two, appetite ratings and plasma acylated ghrelin concentrations were lower in exercise than in control, but energy intake did not differ between trials. The appetite, acylated ghrelin, and energy intake response to exercise did not differ between men and women. Conclusions Women exhibit compensatory appetite, gut hormone, and food intake responses to acute energy restriction but not in response to an acute bout of exercise. Additionally, men and women seem to exhibit similar acylated ghrelin and PYY3–36 responses to exercise-induced energy deficits. These findings advance understanding regarding the interaction between exercise and energy homeostasis in women. PMID:26465216

A neurocomputational account of reward and novelty processing and effects of psychostimulants in attention deficit hyperactivity disorder.

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Sethi, Arjun; Voon, Valerie; Critchley, Hugo D; Cercignani, Mara; Harrison, Neil A

2018-05-01

Computational models of reinforcement learning have helped dissect discrete components of reward-related function and characterize neurocognitive deficits in psychiatric illnesses. Stimulus novelty biases decision-making, even when unrelated to choice outcome, acting as if possessing intrinsic reward value to guide decisions toward uncertain options. Heightened novelty seeking is characteristic of attention deficit hyperactivity disorder, yet how this influences reward-related decision-making is computationally encoded, or is altered by stimulant medication, is currently uncertain. Here we used an established reinforcement-learning task to model effects of novelty on reward-related behaviour during functional MRI in 30 adults with attention deficit hyperactivity disorder and 30 age-, sex- and IQ-matched control subjects. Each participant was tested on two separate occasions, once ON and once OFF stimulant medication. OFF medication, patients with attention deficit hyperactivity disorder showed significantly impaired task performance (P = 0.027), and greater selection of novel options (P = 0.004). Moreover, persistence in selecting novel options predicted impaired task performance (P = 0.025). These behavioural deficits were accompanied by a significantly lower learning rate (P = 0.011) and heightened novelty signalling within the substantia nigra/ventral tegmental area (family-wise error corrected P attention deficit hyperactivity disorder participants' overall task performance (P = 0.011), increased reward-learning rates (P = 0.046) and enhanced their ability to differentiate optimal from non-optimal novel choices (P = 0.032). It also reduced substantia nigra/ventral tegmental area responses to novelty. Preliminary cross-sectional evidence additionally suggested an association between long-term stimulant treatment and a reduction in the rewarding value of novelty. These data suggest that aberrant substantia nigra/ventral tegmental area novelty processing plays an

Word Learning Deficits in Children with Dyslexia

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Alt, Mary; Hogan, Tiffany; Green, Samuel; Gray, Shelley; Cabbage, Kathryn; Cowan, Nelson

2017-01-01

Purpose: The purpose of this study is to investigate word learning in children with dyslexia to ascertain their strengths and weaknesses during the configuration stage of word learning. Method: Children with typical development (N = 116) and dyslexia (N = 68) participated in computer-based word learning games that assessed word learning in 4 sets…

Effects of maternal hyperhomocysteinemia induced by high methionine diet on the learning and memory performance in offspring.

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Baydas, Giyasettin; Koz, Sema T; Tuzcu, Mehmet; Nedzvetsky, Victor S; Etem, Ebru

2007-05-01

In this study, we suggest that chronic maternal hyperhomocysteinemia results in learning deficits in the offspring due to delayed brain maturation and altered expression pattern of neural cell adhesion molecule. Although the deleterious effects of hyperhomocysteinemia were extensively investigated in the adults, there is no clear evidence suggesting its action on the developing fetal rat brain and cognitive functions of the offspring. Therefore, in the present work we aimed to investigate effects of maternal hyperhomocysteinemia on the fetal brain development and on the behavior of the offspring. A group of pregnant rats received daily methionine (1 g/kg body weight) dissolved in drinking water to induce maternal hyperhomocysteinemia, starting in the beginning of gestational day 0. The levels of glial fibrillary acidic protein, S100B protein, and neural cell adhesion molecule were determined in the tissue samples from the pups. Learning and memory performances of the young-adult offsprings were tested using Morris water maze test. There were significant reductions in the expressions of glial fibrillary acidic protein and S100B protein in the brains of maternally hyperhomocysteinemic pups on postnatal day 1, suggesting that hyperhomocysteinemia delays brain maturation. In conclusion, maternal hyperhomocysteinemia changes the expression pattern of neural cell adhesion molecule and therefore leads to an impairment in the learning performance of the offspring.

Edaravone injection reverses learning and memory deficits in a rat model of vascular dementia.

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Li, Xu; Lu, Fen; Li, Wei; Qin, Lingzhi; Yao, Yong; Ge, Xuerong; Yu, Qingkai; Liang, Xinliang; Zhao, Dongmei; Li, Xiaohong; Zhang, Jiewen

2017-01-01

Edaravone is a novel free radical scavenger that exerts neuroprotective effects by inhibiting endothelial injury and by ameliorating neuronal damage in brain ischemia. Recently, it was reported that edaravone could alleviate the pathology and cognitive deficits of Alzheimer's disease patients. However, its relevance to vascular dementia (VaD) is not clear. In this study, we partially occluded the bilateral carotid arteries of rats surgically to induce chronic cerebral hypoperfusion (CCH), a well-known rat model of VaD. Water maze and step-down inhibitory test were used to evaluate the memory deficit. The activities of superoxide dismutase (SOD) and lactate dehydrogenase (LDH), the content of malondialdehyde (MDA) and total reactive oxygen species were measured to evaluate the oxidative stress level. Western blot analysis was used to evaluate the synaptic protein expression. It was found that treatment with edaravone for a 5-week period was able to reverse both spatial and fear-memory deficits in rats with CCH. Edaravone significantly reduced the level of oxidative stress in the brains of rats with CCH by increasing SOD activity and decreasing the content of MDA, LDH, and total reactive oxygen species. Furthermore, edaravone treatment also restored the levels of multiple synaptic proteins in the hippocampi of rats with CCH. Our data provide direct evidence supporting the neuroprotective effects of edaravone in VaD. We propose that the alleviation of oxidative stress and restoration of synaptic proteins play important roles in neuroprotection. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

CHILDREN’S GIFTEDNESS AND ASSOCIATED PROBLEMS. THE TWICE EXCEPTIONALITY PHENOMENON. GIFTEDNESS AND LEARNING PROBLEMS. GIFTEDNESS AND ATTENTION DEFICIT/ HYPERACTIVITY DISORDER (А REVIEW OF LITERATURE. PART I

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O. A. Pylaeva

2015-01-01

Full Text Available In accordance with current views, giftedness are considered as the systemic psychic property developing throughout a lifetime, which determines the human possibility of achieving higher (unusual, outstanding results in one or several kinds of activities as compared to other people. People who are endowed with extraordinary abilities may be infrequently called absolutely somatically and mentally healthy. There are data that giftedness in childhood are frequently concurrent with both somatic diseases and different neurological disorders. Many gifted children are diagnosed as having left-handedness, speech disorders, and autoimmune diseases. There are scientific works on the association of giftedness with neurological and psychiatric disorders, including attention deficit/hyperactivity disorder (ADHD, learning problems (dyslexia in particular, autism (including Asperger’s syndrome, bipolar disorder, and migraine. According to the available data, approximately 3–5 % of children fall into a category of intellectually gifted ones; some children (2–5 to 20 % or more of all gifted children according to different findings may have learning problems. The terms “twice-gifted” or “twice-exceptional” are proposed to characterize children with giftedness concurrent with learning problems, attention deficit (including ADHD, or other impairments of cognitive functions and behavior (including oppositional disorder and obsessive-compulsive disorder. These children need the more attention of teachers and other correction approaches and adaptation methods to be elaborated as compared to the procedures used for gifted children, on the one hand, and for those with learning problems, behavioral and attention disorders, on the other hand. There is a need for the development and further strengthening of strong suits (gift and correction, adaptation of deficits in children with “twice exceptionality”. The review presents the history of studying the �

Neuroprotective effects of phytosterol esters against high cholesterol-induced cognitive deficits in aged rat.

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Rui, Xu; Wenfang, Li; Jing, Cheng; Meng, Chen; Chengcheng, Ding; Jiqu, Xu; Shuang, Rong

2017-03-22

Accumulating epidemiological and experimental studies have confirmed that a high-cholesterol diet is detrimental to cognitive performance in animal models. Phytosterols, a class of naturally occurring structural components in plant foods, have been demonstrated to possess cholesterol-lowering and antioxidant effects. Phytosterol esters (PSE) are esters of phytosterol. The aim of this study was to evaluate the neuroprotective effects of PSE on cognitive deficit induced by a cholesterol-enriched diet in aged rats, and to explore their underlying mechanisms for these effects. Based on their Morris water maze performance, the latencies differed by <1.5 standard deviations (SDs) on days 3-5 of testing, 60 rats were chosen from 12-month-old female Sprague Dawley aged rats and were randomized into three groups, which were fed either a control diet, a high cholesterol diet (HCD) or a high-cholesterol diet supplemented with 2% PSE (HCD + PSE) for 6 months. In our study, we found that PSE treatment maintained the body weight balance, reduced the serum lipid levels, and improved the cognitive performance of aged rats in the Morris water maze test, as evaluated by shortened escape latencies. Importantly, histological and immunohistochemical results in the brain showed that PSE supplementation may have a neuroprotective effect that alleviates neuroinflammation in aged rats. This neuroprotective effect significantly inhibited degeneration, resulting in a significant increase in the number of pyramidal cells and an apparent decrease in the number of astrocytes compared to rats that were fed only a HCD. Furthermore, PSE improved cholinergic activities by restoring the acetylcholine (ACh) content and decreasing acetylcholinesterase (AChE) activity in the cerebral cortex, as well as by elevating choline acetyl transferase (ChAT) activity in the hippocampus and the cerebral cortex. These results suggest that PSE can play a useful role in alleviating cognitive deficit induced by a

Taurine Administration Recovers Motor and Learning Deficits in an Angelman Syndrome Mouse Model

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Sara Guzzetti

2018-04-01

Full Text Available Angelman syndrome (AS, MIM 105830 is a rare neurodevelopmental disorder affecting 1:10–20,000 children. Patients show moderate to severe intellectual disability, ataxia and absence of speech. Studies on both post-mortem AS human brains and mouse models revealed dysfunctions in the extra synaptic gamma-aminobutyric acid (GABA receptors implicated in the pathogenesis. Taurine is a free intracellular sulfur-containing amino acid, abundant in brain, considered an inhibiting neurotransmitter with neuroprotective properties. As taurine acts as an agonist of GABA-A receptors, we aimed at investigating whether it might ameliorate AS symptoms. Since mice weaning, we orally administered 1 g/kg/day taurine in water to Ube3a-deficient mice. To test the improvement of motor and cognitive skills, Rotarod, Novel Object Recognition and Open Field tests were assayed at 7, 14, 21 and 30 weeks, while biochemical tests and amino acid dosages were carried out, respectively, by Western-blot and high-performance liquid chromatography (HPLC on frozen whole brains. Treatment of Ube3am−/p+ mice with taurine significantly improved motor and learning skills and restored the levels of the post-synaptic PSD-95 and pERK1/2-ERK1/2 ratio to wild type values. No side effects of taurine were observed. Our study indicates taurine administration as a potential therapy to ameliorate motor deficits and learning difficulties in AS.

Piracetam improves cognitive deficits caused by chronic cerebral hypoperfusion in rats.

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He, Zhi; Liao, Yun; Zheng, Min; Zeng, Fan-Dian; Guo, Lian-Jun

2008-06-01

Piracetam is the derivate of gamma-aminobutyric acid, which improves the cognition,memory,consciousness, and is widely applied in the clinical treatment of brain dysfunction. In the present experiments, we study the effects of piracetam on chronic cerebral hypoperfused rats and observe its influence on amino acids, synaptic plasticity in the Perforant path-CA3 pathway and apoptosis in vivo. Cerebral hypoperfusion for 30 days by occlusion of bilateral common carotid arteries induced marked amnesic effects along with neuron damage, including: (1) spatial learning and memory deficits shown by longer escape latency and shorter time spent in the target quadrant; (2) significant neuronal loss and nuclei condensation in the cortex and hippocampus especially in CA1 region; (3) lower induction rate of long term potentiation, overexpression of BAX and P53 protein, and lower content of excitatory and inhibitory amino acids in hippocampus. Oral administration of piracetam (600 mg/kg, once per day for 30 days) markedly improved the memory impairment, increased the amino acid content in hippocampus, and attenuated neuronal damage. The ability of piracetam to attenuate memory deficits and neuronal damage after hypoperfusion may be beneficial in cerebrovascular type dementia.

Involvement of nitrergic system of CA1in harmane induced learning and memory deficits.

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Nasehi, Mohammad; Piri, Morteza; Abdollahian, Mojgan; Zarrindast, Mohammad Reza

2013-01-17

Harmane (HA) is a β-carboline alkaloid derived from the Peganum harmala plant which induces memory impairment. On the other hand some of the investigations showed that β-carboline alkaloids inhibit NO production. Thus, the aim of the present study was to investigate the role of nitrergic system of the dorsal hippocampus (CA1) in HA-induced amnesia in male adult mice. One-trial step-down passive avoidance and hole-board apparatuses were used for the assessment of memory retrieval and exploratory behaviors respectively. The data indicated that pre-training intraperitoneal (i.p.) administration of HA (12 and 16 mg/kg) decreased memory acquisition. Sole pre-training or pre-testing administration of L-NAME, a nitric oxide synthesis inhibitor (5, 10 and 15 μg/mice, intra-CA1) did not alter memory retrieval. On the other hand, pre-training (10 and 15 μg/mice, intra-CA1) and pre-testing (5, 10 μg/mice, intra-CA1) injections of L-NAME restored HA-induced amnesia (16 mg/kg, i.p.). Furthermore, neither sole pre-training nor pre-testing administration of l-arginine, a NO precursor (3, 6 and 9 μg/mice, intra-CA1), altered memory retrieval. In addition, pre-testing (6 and 9 μg/mice, intra-CA1), but not pre-training, injection of l-arginine increased HA-induced amnesia (16 mg/kg, i.p.). These results suggest that the nitrergic system of CA1 is involved in HA-induced amnesia. Copyright © 2012 Elsevier Inc. All rights reserved.

The nitric oxide donor sodium nitroprusside attenuates recognition memory deficits and social withdrawal produced by the NMDA receptor antagonist ketamine and induces anxiolytic-like behaviour in rats.

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Trevlopoulou, Aikaterini; Touzlatzi, Ntilara; Pitsikas, Nikolaos

2016-03-01

Experimental evidence indicates that the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine impairs cognition and can mimic certain aspects of positive and negative symptoms of schizophrenia in rodents. Nitric oxide (NO) is considered as an intracellular messenger in the brain, and its abnormalities have been linked to schizophrenia. The present study was designed to investigate the ability of the NO donor sodium nitroprusside (SNP) to counteract schizophrenia-like behavioural deficits produced by ketamine in rats. The ability of SNP to reverse ketamine-induced memory deficits and social withdrawal were assessed using the novel object recognition task (NORT) and the social interaction test, respectively. Furthermore, since anxiety disorders are noted to occur commonly in schizophrenics, the effects of SNP on anxiety-like behaviour were examined using the light/dark test. Locomotor activity was also assessed as an independent measure of the potential motoric effects of this NO donor. SNP (0.3 and 1 mg/kg) reversed ketamine (3 mg/kg)-induced short-term recognition memory deficits. SNP (1 mg/kg) counteracted the ketamine (8 mg/kg)-induced social isolation in the social interaction test. The anxiolytic-like effects in the light/dark test of SNP (1 mg/kg) cannot be attributed to changes in locomotor activity. Our findings illustrate a functional interaction between the nitrergic and glutamatergic system that may be of relevance for schizophrenia-like behavioural deficits. The data also suggest a role of NO in anxiety.

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.

Attention-deficit hyperactivity disorder.

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Meek, D C

1990-09-01

The attention-deficit hyperactivity disorder is a common chronic disorder of childhood. No precise definition or approach to treatment is universally accepted; however, an extensive literature exists on which to base a rational approach to management. Symptomatic treatment with stimulant medication in selected patients is effective and safe, but not curative. Successful outcome depends on multimodality therapy, involving parents, teachers, and other professionals. Associated conditions, including learning disorders and emotional disturbance, must be identified and dealt with.

Musical, visual and cognitive deficits after middle cerebral artery infarction

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Stephanie Rosemann

2017-03-01

Full Text Available The perception of music can be impaired after a stroke. This dysfunction is called amusia and amusia patients often also show deficits in visual abilities, language, memory, learning, and attention. The current study investigated whether deficits in music perception are selective for musical input or generalize to other perceptual abilities. Additionally, we tested the hypothesis that deficits in working memory or attention account for impairments in music perception. Twenty stroke patients with small infarctions in the supply area of the middle cerebral artery were investigated with tests for music and visual perception, categorization, neglect, working memory and attention. Two amusia patients with selective deficits in music perception and pronounced lesions were identified. Working memory and attention deficits were highly correlated across the patient group but no correlation with musical abilities was obtained. Lesion analysis revealed that lesions in small areas of the putamen and globus pallidus were connected to a rhythm perception deficit. We conclude that neither a general perceptual deficit nor a minor domain general deficit can account for impairments in the music perception task. But we find support for the modular organization of the music perception network with brain areas specialized for musical functions as musical deficits were not correlated to any other impairment.

Musical, visual and cognitive deficits after middle cerebral artery infarction.

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Rosemann, Stephanie; Brunner, Freimuth; Kastrup, Andreas; Fahle, Manfred

2017-03-01

The perception of music can be impaired after a stroke. This dysfunction is called amusia and amusia patients often also show deficits in visual abilities, language, memory, learning, and attention. The current study investigated whether deficits in music perception are selective for musical input or generalize to other perceptual abilities. Additionally, we tested the hypothesis that deficits in working memory or attention account for impairments in music perception. Twenty stroke patients with small infarctions in the supply area of the middle cerebral artery were investigated with tests for music and visual perception, categorization, neglect, working memory and attention. Two amusia patients with selective deficits in music perception and pronounced lesions were identified. Working memory and attention deficits were highly correlated across the patient group but no correlation with musical abilities was obtained. Lesion analysis revealed that lesions in small areas of the putamen and globus pallidus were connected to a rhythm perception deficit. We conclude that neither a general perceptual deficit nor a minor domain general deficit can account for impairments in the music perception task. But we find support for the modular organization of the music perception network with brain areas specialized for musical functions as musical deficits were not correlated to any other impairment.

High concentration of vitamin E decreases thermosensation and thermotaxis learning and the underlying mechanisms in the nematode Caenorhabditis elegans.

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Li, Yiping; Li, Yinxia; Wu, Qiuli; Ye, Huayue; Sun, Lingmei; Ye, Boping; Wang, Dayong

2013-01-01

α-tocopherol is a powerful liposoluble antioxidant and the most abundant isoform of vitamin E in the body. Under normal physiological conditions, adverse effects of relatively high concentration of vitamin E on organisms and the underlying mechanisms are still largely unclear. In the present study, we used the nematode Caenorhabditis elegans as an in vivo assay system to investigate the possible adverse effects of high concentration of vitamin E on thermosensation and thermotaxis learning and the underlying mechanisms. Our data show that treatment with 100-200 µg/mL of vitamin E did not noticeably influence both thermosensation and thermotaxis learning; however, treatment with 400 µg/mL of vitamin E altered both thermosensation and thermotaxis learning. The observed decrease in thermotaxis learning in 400 µg/mL of vitamin E treated nematodes might be partially due to the moderate but significant deficits in thermosensation, but not due to deficits in locomotion behavior or perception to food and starvation. Treatment with 400 µg/mL of vitamin E did not noticeably influence the morphology of GABAergic neurons, but significantly decreased fluorescent intensities of the cell bodies in AFD sensory neurons and AIY interneurons, required for thermosensation and thermotaxis learning control. Treatment with 400 µg/mL of vitamin E affected presynaptic function of neurons, but had no remarkable effects on postsynaptic function. Moreover, promotion of synaptic transmission by activating PKC-1 effectively retrieved deficits in both thermosensation and thermotaxis learning induced by 400 µg/mL of vitamin E. Therefore, relatively high concentrations of vitamin E administration may cause adverse effects on thermosensation and thermotaxis learning by inducing damage on the development of specific neurons and presynaptic function under normal physiological conditions in C. elegans.

Exposure to 56Fe irradiation accelerates normal brain aging and produces deficits in spatial learning and memory

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Shukitt-Hale, Barbara; Casadesus, Gemma; Carey, Amanda N.; Rabin, Bernard M.; Joseph, James A.

Previous studies have shown that radiation exposure, particularly to particles of high energy and charge (HZE particles) such as 56Fe, 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. For example, an increased release of reactive oxygen species, and the subsequent oxidative stress and inflammatory damage caused to the central nervous system, is likely responsible for the deficits seen in aging and following irradiation. Therefore, dietary antioxidants, such as those found in fruits and vegetables, could be used as countermeasures to prevent the behavioral changes seen in these conditions. 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 56Fe high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts, particularly middle-aged ones, to perform critical tasks during long-term space travel beyond the magnetosphere.

Neuroprotective influence of taurine on fluoride-induced biochemical and behavioral deficits in rats.

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Adedara, Isaac A; Abolaji, Amos O; Idris, Umar F; Olabiyi, Bolanle F; Onibiyo, Esther M; Ojuade, TeminiJesu D; Farombi, Ebenezer O

2017-01-05

Epidemiological and experimental studies have demonstrated that excessive exposure to fluoride induced neurodevelopmental toxicity both in humans and animals. Taurine is a free intracellular β-amino acid with antioxidant and neuroprotective properties. The present study investigated the neuroprotective mechanism of taurine by evaluating the biochemical and behavioral characteristics in rats exposed to sodium fluoride (NaF) singly in drinking water at 15 mg/L alone or orally co-administered by gavage with taurine at 100 and 200 mg/kg body weight for 45 consecutive days. Locomotor behavior was assessed using video-tracking software during a 10-min trial in a novel environment while the brain structures namely the hypothalamus, cerebrum and cerebellum of the rats were processed for biochemical determinations. Results showed that taurine administration prevented NaF-induced locomotor and motor deficits namely decrease in total distance travelled, total body rotation, maximum speed, absolute turn angle along with weak forelimb grip, increased incidence of fecal pellets and time of grooming, immobility and negative geotaxis. The taurine mediated enhancement of the exploratory profiles of NaF-exposed rats was supported by track and occupancy plot analyses. Moreover, taurine prevented NaF-induced increase in hydrogen peroxide and lipid peroxidation levels but increased acetylcholinesterase and the antioxidant enzymes activities in the hypothalamus, cerebrum and cerebellum of the rats. Collectively, taurine protected against NaF-induced neurotoxicity via mechanisms involving the restoration of acetylcholinesterase activity and antioxidant status with concomitant inhibition of lipid peroxidation in the brain of rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of novel tacrine-related cholinesterase inhibitors in the reversal of 3-quinuclidinyl benzilate-induced cognitive deficit in rats--Is there a potential for Alzheimer's disease treatment?

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Misik, Jan; Korabecny, Jan; Nepovimova, Eugenie; Kracmarova, Alzbeta; Kassa, Jiri

2016-01-26

Inhibitors of cholinesterase are important drugs for therapy of Alzheimer's disease and the search for new modifications is extensive, including dual inhibitors or multi-target hybrid compounds. The aim of the present study was a preliminary evaluation of pro-cognitive effects of newly-developed 7-MEOTA-donepezil like hybrids (compounds no. 1 and 2) and N-alkylated tacrine derivatives (compounds no. 3 and 4) using an animal model of pharmacologically-induced cognitive deficit. Male Wistar rats were subjected to tests of learning and memory in a water maze and step-through passive avoidance task. Cognitive impairment was induced by 3-quinuclidinyl benzilate (QNB, 2mgkg(-1)), administered intraperitoneally 1h before training sessions. Cholinesterase inhibitors were administered as a single therapeutic dose following the QNB at 30min at the following dose rates; 1 (25.6mgkg(-1)), 2 (12.3mgkg(-1)), 3 (5.7mgkg(-1)), 4 (5.2mgkg(-1)). The decrease in total path within the 10-swim session (water maze), the preference for target quadrant (water maze) and the entrance latency (passive avoidance) were taken as indicators of learning ability in rats. The effects of novel compounds were compared to that of standards tacrine (5.2mgkg(-1)) and donepezil (2.65mgkg(-1)). QNB significantly impaired spatial navigation as well as fear learning. Generally, the performance of rats was improved when treated with novel inhibitors and this effect reached efficiency of standard donepezil at selected doses. There was a significant improvement in the groups treated with compounds 2 and 3 in all behavioral tasks. The rest of the novel compounds succeed in the passive avoidance test. In summary, the potential of novel inhibitors (especially compounds 2 and 3) was proved and further detailed evaluation of these compounds as potential drugs for Alzheimer's disease treatment is proposed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cognitive deficits are a matter of emotional context: inflexible strategy use mediates context-specific learning impairments in OCD.

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Zetsche, Ulrike; Rief, Winfried; Westermann, Stefan; Exner, Cornelia

2015-01-01

The present study examines the interplay between cognitive deficits and emotional context in obsessive-compulsive disorder (OCD) and social phobia (SP). Specifically, this study examines whether the inflexible use of efficient learning strategies in an emotional context underlies impairments in probabilistic classification learning (PCL) in OCD, and whether PCL impairments are specific to OCD. Twenty-three participants with OCD, 30 participants with SP and 30 healthy controls completed a neutral and an OCD-specific PCL task. OCD participants failed to adopt efficient learning strategies and showed fewer beneficial strategy switches than controls only in an OCD-specific context, but not in a neutral context. Additionally, OCD participants did not show any explicit memory impairments. Number of beneficial strategy switches in the OCD-specific task mediated the difference in PCL performance between OCD and control participants. Individuals with SP were impaired in both PCL tasks. In contrast to neuropsychological models postulating general cognitive impairments in OCD, the present findings suggest that it is the interaction between cognition and emotion that is impaired in OCD. Specifically, activated disorder-specific fears may impair the flexible adoption of efficient learning strategies and compromise otherwise unimpaired PCL. Impairments in PCL are not specific to OCD.

Toward A Dual-Learning Systems Model of Speech Category Learning

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Bharath eChandrasekaran

2014-07-01

Full Text Available More than two decades of work in vision posits the existence of dual-learning systems of category learning. The reflective system uses working memory to develop and test rules for classifying in an explicit fashion, while the reflexive system operates by implicitly associating perception with actions that lead to reinforcement. Dual-learning systems models hypothesize that in learning natural categories, learners initially use the reflective system and, with practice, transfer control to the reflexive system. The role of reflective and reflexive systems in auditory category learning and more specifically in speech category learning has not been systematically examined. In this article we describe a neurobiologically-constrained dual-learning systems theoretical framework that is currently being developed in speech category learning and review recent applications of this framework. Using behavioral and computational modeling approaches, we provide evidence that speech category learning is predominantly mediated by the reflexive learning system. In one application, we explore the effects of normal aging on non-speech and speech category learning. We find an age related deficit in reflective-optimal but not reflexive-optimal auditory category learning. Prominently, we find a large age-related deficit in speech learning. The computational modeling suggests that older adults are less likely to transition from simple, reflective, uni-dimensional rules to more complex, reflexive, multi-dimensional rules. In a second application we summarize a recent study examining auditory category learning in individuals with elevated depressive symptoms. We find a deficit in reflective-optimal and an enhancement in reflexive-optimal auditory category learning. Interestingly, individuals with elevated depressive symptoms also show an advantage in learning speech categories. We end with a brief summary and description of a number of future directions.

CREB Selectively Controls Learning-Induced Structural Remodeling of Neurons

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Middei, Silvia; Spalloni, Alida; Longone, Patrizia; Pittenger, Christopher; O'Mara, Shane M.; Marie, Helene; Ammassari-Teule, Martine

2012-01-01

The modulation of synaptic strength associated with learning is post-synaptically regulated by changes in density and shape of dendritic spines. The transcription factor CREB (cAMP response element binding protein) is required for memory formation and in vitro dendritic spine rearrangements, but its role in learning-induced remodeling of neurons…

Working memory deficits in children with specific learning disorders.

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Schuchardt, Kirsten; Maehler, Claudia; Hasselhorn, Marcus

2008-01-01

This article examines working memory functioning in children with specific developmental disorders of scholastic skills as defined by ICD-10. Ninety-seven second to fourth graders with a minimum IQ of 80 are compared using a 2 x 2 factorial (dyscalculia vs. no dyscalculia; dyslexia vs. no dyslexia) design. An extensive test battery assesses the three subcomponents of working memory described by Baddeley (1986): phonological loop, visual-spatial sketchpad, and central executive. Children with dyscalculia show deficits in visual-spatial memory; children with dyslexia show deficits in phonological and central executive functioning. When controlling for the influence of the phonological loop on the performance of the central executive, however, the effect is no longer significant. Although children with both reading and arithmetic disorders are consistently outperformed by all other groups, there is no significant interaction between the factors dyscalculia and dyslexia.

Effect of pregabalin on contextual memory deficits and inflammatory state-related protein expression in streptozotocin-induced diabetic mice.

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Sałat, Kinga; Gdula-Argasińska, Joanna; Malikowska, Natalia; Podkowa, Adrian; Lipkowska, Anna; Librowski, Tadeusz

2016-06-01

Diabetes mellitus is a metabolic disease characterized by hyperglycemia due to defects in insulin secretion or its action. Complications from long-term diabetes consist of numerous biochemical, molecular, and functional tissue alterations, including inflammation, oxidative stress, and neuropathic pain. There is also a link between diabetes mellitus and vascular dementia or Alzheimer's disease. Hence, it is important to treat diabetic complications using drugs which do not aggravate symptoms induced by the disease itself. Pregabalin is widely used for the treatment of diabetic neuropathic pain, but little is known about its impact on cognition or inflammation-related proteins in diabetic patients. Thus, this study aimed to evaluate the effect of intraperitoneal (ip) pregabalin on contextual memory and the expression of inflammatory state-related proteins in the brains of diabetic, streptozotocin (STZ)-treated mice. STZ (200 mg/kg, ip) was used to induce diabetes mellitus. To assess the impact of pregabalin (10 mg/kg) on contextual memory, a passive avoidance task was applied. Locomotor and exploratory activities in pregabalin-treated diabetic mice were assessed by using activity cages. Using Western blot analysis, the expression of cyclooxygenase-2 (COX-2), cytosolic prostaglandin E synthase (cPGES), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), nuclear factor-ĸB (NF-ĸB) p50 and p65, aryl hydrocarbon receptor (AhR), as well as glucose transporter type-4 (GLUT4) was assessed in mouse brains after pregabalin treatment. Pregabalin did not aggravate STZ-induced learning deficits in vivo or influence animals' locomotor activity. We observed significantly lower expression of COX-2, cPGES, and NF-κB p50 subunit, and higher expression of AhR and Nrf2 in the brains of pregabalin-treated mice in comparison to STZ-treated controls, which suggested immunomodulatory and anti-inflammatory effects of pregabalin. Antioxidant properties of pregabalin in the brains of

The effect of chronic phenytoin administration on single prolonged stress induced extinction retention deficits and glucocorticoid upregulation in the rat medial prefrontal cortex.

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George, Sophie A; Rodriguez-Santiago, Mariana; Riley, John; Rodriguez, Elizabeth; Liberzon, Israel

2015-01-01

Post-traumatic stress disorder (PTSD) is a chronic, debilitating disorder. Only two pharmacological agents are approved for PTSD treatment, and they often do not address the full range of symptoms nor are they equally effective in all cases. Animal models of PTSD are critical for understanding the neurobiology involved and for identification of novel therapeutic targets. Using the rodent PTSD model, single prolonged stress (SPS), we have implicated aberrant excitatory neural transmission and glucocorticoid receptor (GR) upregulation in the medial prefrontal cortex (mPFC) and hippocampus (HPC) in fear memory abnormalities associated with PTSD. The objective of this study is to examine the potential protective effect of antiepileptic phenytoin (PHE) administration on SPS-induced extinction retention deficits and GR expression. Forty-eight SPS-treated male Sprague Dawley rats or controls were administered PHE (40, 20 mg/kg, vehicle) for 7 days following SPS stressors; then, fear conditioning, extinction, and extinction retention were tested. Fear conditioning and extinction were unaffected by SPS or PHE, but SPS impaired extinction retention, and both doses of PHE rescued this impairment. Similarly, SPS increased GR expression in the mPFC and dorsal HPC, and PHE prevented SPS-induced GR upregulation in the mPFC. These data demonstrate that PHE administration can prevent the development of extinction retention deficits and upregulation of GR. PHE exerts inhibitory effects on voltage-gated sodium channels and decreases excitatory neural transmission via glutamate antagonism. If glutamate hyperactivity in the days following SPS contributes to SPS-induced deficits, then these data may suggest that the glutamatergic system constitutes a target for secondary prevention.

Brain signaling and behavioral responses induced by exposure to (56)Fe-particle radiation

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Denisova, N. A.; Shukitt-Hale, B.; Rabin, B. M.; Joseph, J. A.

2002-01-01

Previous experiments have demonstrated that exposure to 56Fe-particle irradiation (1.5 Gy, 1 GeV) produced aging-like accelerations in neuronal and behavioral deficits. Astronauts on long-term space flights will be exposed to similar heavy-particle radiations that might have similar deleterious effects on neuronal signaling and cognitive behavior. Therefore, the present study evaluated whether radiation-induced spatial learning and memory behavioral deficits are associated with region-specific brain signaling deficits by measuring signaling molecules previously found to be essential for behavior [pre-synaptic vesicle proteins, synaptobrevin and synaptophysin, and protein kinases, calcium-dependent PRKCs (also known as PKCs) and PRKA (PRKA RIIbeta)]. The results demonstrated a significant radiation-induced increase in reference memory errors. The increases in reference memory errors were significantly negatively correlated with striatal synaptobrevin and frontal cortical synaptophysin expression. Both synaptophysin and synaptobrevin are synaptic vesicle proteins that are important in cognition. Striatal PRKA, a memory signaling molecule, was also significantly negatively correlated with reference memory errors. Overall, our findings suggest that radiation-induced pre-synaptic facilitation may contribute to some previously reported radiation-induced decrease in striatal dopamine release and for the disruption of the central dopaminergic system integrity and dopamine-mediated behavior.

Plasma membrane ordering agent pluronic F-68 (PF-68) reduces neurotransmitter uptake and release and produces learning and memory deficits in rats

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Clarke, M. S.; Prendergast, M. A.; Terry, A. V. Jr

1999-01-01

performance, or in tests of general locomotor activity. Furthermore, latencies to select a lever in the DSDT were not affected. These results suggest that PF-68 induced deficits in learning and memory without confounding peripheral motor, sensory, or motivational effects at the tested doses. Furthermore, none of the doses induced a conditioned taste aversion to a novel 0.1% saccharin solution indicating a lack of nausea or gastrointestinal malaise induced by the compound. The data indicate that increases in neuronal plasma membrane order may have significant effects on neurotransmitter function as well as learning and memory processes. Furthermore, compounds such as PF-68 may also offer novel tools for studying the role of neuronal PMO in mnemonic processes and changes in PMO resulting from age-related disorders such as AD.

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.

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

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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…

Comparing dictionary-induced vocabulary learning and inferencing ...

African Journals Online (AJOL)

This research examines dictionary-induced vocabulary learning and inferencing in the context of reading. One hundred and four intermediate English learners completed one of two word-focused tasks: reading comprehension and dictionary consultation, and reading comprehen-sion and inferencing. In addition to ...

Comorbidity of Learning Disorders and Attention Deficit Hyperactivity Disorder in a Sample of Omani Schoolchildren

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Watfa S. Al-Mamari

2015-11-01

Full Text Available Objectives: The estimated worldwide prevalence of learning disorders (LDs is approximately 2‒10% among school-aged children. LDs have variable clinical features and are often associated with other disorders. This study aimed to examine the comorbidity of LDs and attention deficit hyperactivity disorder (ADHD among a sample of schoolchildren in Oman. Methods: This study was conducted between January 2014 and January 2015 at the Sultan Qaboos University, Muscat, Oman. The Learning Disabilities Diagnostic Inventory (LDDI and the 28- item version of the Conners’ Teacher Rating Scale was completed by classroom teachers to determine the existence of LD and ADHD symptoms in 321 children in grades 1‒4 who had been referred to a learning support unit for LDs from elementary schools in Muscat. Results: The mean age of the students was 8.5 years. Among the cohort, 30% were reported to have symptoms of ADHD, including conduct problems (24%, hyperactivity (24% and inattentivepassive behaviours (41%. Male students reportedly exhibited greater conduct problems and hyperactivity than females. However, there were no gender differences noted between LDDI scores. Conclusion: This study suggests that Omani schoolchildren with LDs are likely to exhibit signs of ADHD. The early identification of this disorder is essential considering the chronic nature of ADHD. For interventional purposes, multidisciplinary teams are recommended, including general and special educators, clinical psychologists, school counsellors, developmental or experienced general paediatricians and child psychiatrists.

A aprendizagem simbólica em crianças com deficit atencional Simbolic learnig in children with attention deficit

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Gladys Mabel Duarte

2006-12-01

Full Text Available Foram participantes deste estudo seis crianças da escola regular, das quais três apresentavam distúrbios atencionais associados a dificuldades de aprendizagem escolar. Todas as crianças foram submetidas a sete experimentos visando avaliar a formação de classes de equivalência. O procedimento incluiu a manipulação de diferentes variáveis tais como estrutura de treino, aspectos dimensionais dos estímulos e contingências de reforçamento, com o objetivo de analisar o impacto destes fatores na formação de classes. Os dados mostram que as mudanças na natureza dos reforçamentos parece m ser altamente críticas para induzir respostas de observação e o incremento na precisão das respostas de emparelhamento de acordo com o modelo. O treino multinodal (experimento 6 e o tamanho das classes (experimento 1 e 2 mostraram uma diminuição dos efeitos negativos dos distúrbios atencionais nas três crianças do grupo experimental. Os resultados do estudo foram discutidos em termos das possíveis tecnologias de ensino que poderiam reduzir as conseqüências dos deficits atencionais e os comportamentos impulsivos no desempenho acadêmico.Six children from regular schools, three of them with ADHD (attention deficit/hiperactivity disorder and learning disabilities, were submitted to seven experiments in order to evaluate equivalence class formation. The procedure included the manipulation of different variables, such as training structure, dimensional features of stimuli and reinforcing contingencies, in order to asses the impact of these factors on class formation. The obtained data showed that the changes in reinforcing nature seem to be quite critical in inducing observation responses, and heightening accuracy in matching according to the model. Multinodal training (in experiment 6 and size class (in experiment 1 and 2 diminished the "negative effects" of attention deficits in the three participants with ADHD. The results were discussed in

TNF-α protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation

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Belarbi Karim

2012-01-01

Full Text Available Abstract Background Chronic neuroinflammation is a hallmark of several neurological disorders associated with cognitive loss. Activated microglia and secreted factors such as tumor necrosis factor (TNF-α are key mediators of neuroinflammation and may contribute to neuronal dysfunction. Our study was aimed to evaluate the therapeutic potential of a novel analog of thalidomide, 3,6'-dithiothalidomide (DT, an agent with anti-TNF-α activity, in a model of chronic neuroinflammation. Methods Lipopolysaccharide or artificial cerebrospinal fluid was infused into the fourth ventricle of three-month-old rats for 28 days. Starting on day 29, animals received daily intraperitoneal injections of DT (56 mg/kg/day or vehicle for 14 days. Thereafter, cognitive function was assessed by novel object recognition, novel place recognition and Morris water maze, and animals were euthanized 25 min following water maze probe test evaluation. Results Chronic LPS-infusion was characterized by increased gene expression of the proinflammatory cytokines TNF-α and IL-1β in the hippocampus. Treatment with DT normalized TNF-α levels back to control levels but not IL-1β. Treatment with DT attenuated the expression of TLR2, TLR4, IRAK1 and Hmgb1, all genes involved in the TLR-mediated signaling pathway associated with classical microglia activation. However DT did not impact the numbers of MHC Class II immunoreactive cells. Chronic neuroinflammation impaired novel place recognition, spatial learning and memory function; but it did not impact novel object recognition. Importantly, treatment with DT restored cognitive function in LPS-infused animals and normalized the fraction of hippocampal neurons expressing the plasticity-related immediate-early gene Arc. Conclusion Our data demonstrate that the TNF-α synthesis inhibitor DT can significantly reverse hippocampus-dependent cognitive deficits induced by chronic neuroinflammation. These results suggest that TNF-α is a

Reduced brain-derived neurotrophic factor expression in cortex and hippocampus involved in the learning and memory deficit in molarless SAMP8 mice

Institute of Scientific and Technical Information of China (English)

JIANG Qing-song; LIANG Zi-liang; WU Min-Jie; FENG Lin; LIU Li-li; ZHANG Jian-jun

2011-01-01

Background The molarless condition has been reported to compromise learning and memory functions. However, it remains unclear how the molarless condition directly affects the central nervous system, and the functional consequences on the brain cortex and hippocampus have not been described in detail. The aim of this study was to find the molecular mechanism related with learning and memory deficit after a bilateral molarless condition having been surgically induced in senescence-accelerated mice/prone8 (SAMP8) mice, which may ultimately provide an experimental basis for clinical prevention of senile dementia.Methods Mice were either sham-operated or subjected to complete molar removal. The animals' body weights were monitored every day. Learning ability and memory were measured in a water maze test at the end of the 1 st, 2nd, and 3rd months after surgery. As soon as significantly prolonged escape latency in the molarless group was detected, the locomotor activity was examined in an open field test. Subsequently, the animals were decapitated and the cortex and hippocampus were dissected for Western blotting to measure the expression levels of brain-derived neurotrophic factor (BDNF) and the tropomyosin related kinase B (TrkB), the high affinity receptor of BDNF.Results Slightly lower weights were consistently observed in the molarless group, but there was no significant difference in weights between the two groups (P＞0.05). Compared with the sham group, the molarless group exhibited lengthened escape latency in the water maze test three months after surgery, whereas no difference in locomotor activity was observed. Meanwhile, in the cortex and hippocampus, BDNF levels were significantly decreased in the molarless group (P＜0.05); but the expression of its receptor, TrkB, was not significantly affected.Conclusion These results suggested that the molarless condition impaired learning and memory abilities in SAMP8mice three months after teeth extraction, and this

N-methyl-d-aspartate receptors, learning and memory: chronic intraventricular infusion of the NMDA receptor antagonist d-AP5 interacts directly with the neural mechanisms of spatial learning.

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Morris, R G M; Steele, R J; Bell, J E; Martin, S J

2013-03-01

Three experiments were conducted to contrast the hypothesis that hippocampal N-methyl-d-aspartate (NMDA) receptors participate directly in the mechanisms of hippocampus-dependent learning with an alternative view that apparent impairments of learning induced by NMDA receptor antagonists arise because of drug-induced neuropathological and/or sensorimotor disturbances. In experiment 1, rats given a chronic i.c.v. infusion of d-AP5 (30 mm) at 0.5 μL/h were selectively impaired, relative to aCSF-infused animals, in place but not cued navigation learning when they were trained during the 14-day drug infusion period, but were unimpaired on both tasks if trained 11 days after the minipumps were exhausted. d-AP5 caused sensorimotor disturbances in the spatial task, but these gradually worsened as the animals failed to learn. Histological assessment of potential neuropathological changes revealed no abnormalities in d-AP5-treated rats whether killed during or after chronic drug infusion. In experiment 2, a deficit in spatial learning was also apparent in d-AP5-treated rats trained on a spatial reference memory task involving two identical but visible platforms, a task chosen and shown to minimise sensorimotor disturbances. HPLC was used to identify the presence of d-AP5 in selected brain areas. In Experiment 3, rats treated with d-AP5 showed a delay-dependent deficit in spatial memory in the delayed matching-to-place protocol for the water maze. These data are discussed with respect to the learning mechanism and sensorimotor accounts of the impact of NMDA receptor antagonists on brain function. We argue that NMDA receptor mechanisms participate directly in spatial learning. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Offsetting deficit conceptualisations: methodological considerations for higher education research

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Lynn Coleman

2016-06-01

Full Text Available This paper contributes to the current introspection in the academic development community that critiques the persistent conceptualisations of students as deficient. Deficit discourses are also implicated in many of the student support, curriculum and pedagogic initiatives employed across the higher education sector. The argument developed here, unlike most of the existing debates which focus on pedagogic or institutional initiatives, explores how the research interests and methodological choices of academic developers and researchers could incorporate sensitivity against deficit conceptions and foster more contextualised accounts of students and their learning. This article uses an ethnographic study into the assignment practices of vocational higher education students to show how certain methodological and theoretical choices engender anti-deficit conceptualisations. The study’s analytic framework uses the concepts of literacy practices and knowledge recontextualisation to place analytic attention on both the students’ assignment practices and the influence of curriculum decision making on such practices. The significance of this dual focus is its ability to capture the complexity of students’ meaning-making during assignment production, without remaining silent about the structuring influence of the curriculum. I argue in this paper that the focus on both students and curriculum is able to offer contextualised accounts of students’ interpretations and enacted experiences of their assessment and curriculum environment. Exploring the multidimensional nature of student learning experiences in ways that accommodate the influence of various contextual realities brings researchers and their research agendas closer to offsetting deficit conceptualisation.

Effects of the hydroalcoholic extract of Rosa damascena on learning and memory in male rats consuming a high-fat diet.

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Rezvani-Kamran, Arezoo; Salehi, Iraj; Shahidi, Siamak; Zarei, Mohammad; Moradkhani, Shirin; Komaki, Alireza

2017-12-01

High-fat diet (HFD) can cause deficits in learning and memory through oxidative stress and increase Alzheimer disease risk. Rosa damascena Mill. (Rosaceae) extract possesses potent antioxidant properties. This study investigated the effects of the hydroalcoholic extracts of petals of R. damascena on learning and memory in male rats consuming an HFD. Forty male Wistar rats (200-250 g) were randomly assigned to four groups: control, R. damascena extract, HFD and HFD + extract. The extract (1 g/kg bw daily) was administered by oral gavage for 1 month. Animals were allowed free access to high-fat chow for 3 months. The Morris water maze and the passive avoidance learning tests were used to assess learning and memory. In the passive avoidance learning test, the step-through latencies in the retention test (STLr) of the extract (147.4 ± 23.3) and HFD (150.3 ± 25.2) groups were significantly lower than those of the control group (270.4 ± 10.5) (respectively, p memory deficits, R. damascena extract exerted a positive effect on HFD-induced memory deficits. We hypothesize that the observed effects of R. damascena extract are likely due to its strong antioxidant properties.

Forebrain-specific knockout of B-raf kinase leads to deficits in hippocampal long-term potentiation, learning, and memory.

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Chen, Adele P; Ohno, Masuo; Giese, K Peter; Kühn, Ralf; Chen, Rachel L; Silva, Alcino J

2006-01-01

Raf kinases are downstream effectors of Ras and upstream activators of the MEK-ERK cascade. Ras and MEK-ERK signaling play roles in learning and memory (L&M) and neural plasticity, but the roles of Raf kinases in L&M and plasticity are unclear. Among Raf isoforms, B-raf is preferentially expressed in the brain. To determine whether B-raf has a role in synaptic plasticity and L&M, we used the Cre-LoxP gene targeting system to derive forebrain excitatory neuron B-raf knockout mice. This conditional knockout resulted in deficits in ERK activation and hippocampal long-term potentiation (LTP) and impairments in hippocampus-dependent L&M, including spatial learning and contextual discrimination. Despite the widespread expression of B-raf, this mutation did not disrupt other forms of L&M, such as cued fear conditioning and conditioned taste aversion. Our findings demonstrate that B-raf plays a role in hippocampal ERK activation, synaptic plasticity, and L&M.

Estradiol-induced neurogenesis in the female accessory olfactory bulb is required for the learning of the male odor.

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Brus, Maïna; Trouillet, Anne-Charlotte; Hellier, Vincent; Bakker, Julie

2016-08-01

Odors processed by the main and accessory olfactory bulbs (MOB, AOB) are important for sexual behavior. Interestingly, both structures continue to receive new neurons during adulthood. A role for olfactory neurogenesis in sexual behavior in female mice has recently been shown and gonadal hormones such as estradiol can modulate adult neurogenesis. Therefore, we wanted to determine the role of estradiol in learning the odors of sexual partners and in the adult neurogenesis of female aromatase knockout mice (ArKO), unable to produce estradiol. Female wild-type (WT) and ArKO mice were exposed to male odors during 7 days, and olfactory preferences, cell proliferation, cell survival and functional involvement of newborn neurons were analyzed, using BrdU injections, in combination with a marker of cell activation (Zif268) and neuronal fate (doublecortin, NeuN). Behavioral tasks indicated that both WT and ArKO females were able to discriminate between the odors of two different males, but ArKO mice failed to learn the familiar male odor. Proliferation of newborn cells was reduced in ArKO mice only in the dentate gyrus of the hippocampus. Olfactory exposure decreased cell survival in the AOB in WT females, suggesting a role for estradiol in a structure involved in sexual behavior. Finally, newborn neurons do not seem to be functionally involved in the AOB of ArKO mice compared with WT, when females were exposed to the odor of a familiar male, suggesting that estradiol-induced neurogenesis in the AOB is required for the learning of the male odor in female mice. Aromatase knockout mice (ArKO) presented deficits in olfactory preferences without affecting their olfactory discrimination abilities, and showed no functional involvement of newborn neurons in the accessory olfactory bulb (AOB) in response to the odor of a familiar male. These results suggest that estradiol-induced neurogenesis in the female AOB is required for the learning of the male odor. © 2016 International

The Effect of an NCAM Mimetic on Learning and Memory Impairment in an Animal Model of Schizophrenia

DEFF Research Database (Denmark)

Secher, Thomas

2009-01-01

by immunohistochemical investigation of neurodegeneration and NMDA receptor activation in relevant brain regions. The results show that neonatal PCP treatment induces long-term impairment in spatial learning and memory. The higher PCP dose produced more robust deficits in all three tasks of the water maze, whereas...... for schizophrenia. Neonatal treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (PCP) on postnatal days 7, 9, and 11 has been shown to induce acute neurodegeneration and long-term cognitive deficits and other behavioral abnormalities relevant to schizophrenia. To evaluate the effect...... results indicated that FGL treatment was able to reduce apoptotic cell death in the frontal cortex in pups and to increase NMDA receptor activation in the hippocampus in adults In the present project, further evidence was obtained that neonatal PCP treatment induces long-term impairment in spatial...

Pacific Ciguatoxin Induces Excitotoxicity and Neurodegeneration in the Motor Cortex Via Caspase 3 Activation: Implication for Irreversible Motor Deficit.

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Asthana, Pallavi; Zhang, Ni; Kumar, Gajendra; Chine, Virendra Bhagawan; Singh, Kunal Kumar; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

2018-01-18

Consumption of fish containing ciguatera toxins or ciguatoxins (CTXs) causes ciguatera fish poisoning (CFP). In some patients, CFP recurrence occurs even years after exposure related to CTXs accumulation. Pacific CTX-1 (P-CTX-1) is one of the most potent natural substances known that causes predominantly neurological symptoms in patients; however, the underlying pathogenies of CFP remain unknown. Using clinically relevant neurobehavioral tests and electromyography (EMG) to assess effects of P-CTX-1 during the 4 months after exposure, recurrent motor strength deficit occurred in mice exposed to P-CTX-1. We detected irreversible motor strength deficits accompanied by reduced EMG activity, demyelination, and slowing of motor nerve conduction, whereas control unexposed mice fully recovered in 1 month after peripheral nerve injury. Finally, to uncover the mechanism underlying CFP, we detected reduction of spontaneous firing rate of motor cortical neurons even 6 months after exposure and increased number of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes. Increased numbers of motor cortical neuron apoptosis were detected by dUTP-digoxigenin nick end labeling assay along with activation of caspase 3. Taken together, our study demonstrates that persistence of P-CTX-1 in the nervous system induces irreversible motor deficit that correlates well with excitotoxicity and neurodegeneration detected in the motor cortical neurons.

Reduction of the Misinformation Effect by Arousal Induced after Learning

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English, Shaun M.; Nielson, Kristy A.

2010-01-01

Misinformation introduced after events have already occurred causes errors in later retrieval. Based on literature showing that arousal induced after learning enhances delayed retrieval, we investigated whether post-learning arousal can reduce the misinformation effect. 251 participants viewed four short film clips, each followed by a retention…

Chronic Treatment with Squid Phosphatidylserine Activates Glucose Uptake and Ameliorates TMT-Induced Cognitive Deficit in Rats via Activation of Cholinergic Systems

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Hyun-Jung Park

2012-01-01

Full Text Available The present study examined the effects of squid phosphatidylserine (Squid-PS on the learning and memory function and the neural activity in rats with TMT-induced memory deficits. The rats were administered saline or squid derived Squid-PS (Squid-PS 50 mg kg−1, p.o. daily for 21 days. The cognitive improving efficacy of Squid-PS on the amnesic rats, which was induced by TMT, was investigated by assessing the passive avoidance task and by performing choline acetyltransferase (ChAT and acetylcholinesterase (AchE immunohistochemistry. 18F-Fluorodeoxyglucose and performed a positron emission tomography (PET scan was also performed. In the passive avoidance test, the control group which were injected with TMT showed a markedly lower latency time than the non-treated normal group (P<0.05. However, treatment of Squid-PS significantly recovered the impairment of memory compared to the control group (P<0.05. Consistent with the behavioral data, Squid-PS significantly alleviated the loss of ChAT immunoreactive neurons in the hippocampal CA3 compared to that of the control group (P<0.01. Also, Squid-PS significantly increased the AchE positive neurons in the hippocampal CA1 and CA3. In the PET analysis, Squid-PS treatment increased the glucose uptake more than twofold in the frontal lobe and the hippocampus (P<0.05, resp.. These results suggest that Squid-PS may be useful for improving the cognitive function via regulation of cholinergic enzyme activity and neural activity.

The effect of combined treatment with risperidone and antidepressants on the MK-801-induced deficits in the social interaction test in rats.

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Kamińska, Katarzyna; Rogóż, Zofia

2015-12-01

Several clinical reports have suggested that augmentation of atypical antipsychotics' activity by antidepressants may efficiently improve the treatment of negative and some cognitive symptoms of schizophrenia. The aim of the present study was to investigate the effect of antidepressant mirtazapine or escitalopram and risperidone (an atypical antipsychotic), given separately or jointly, on the MK-801-induced deficits in the social interaction test in rats. Antidepressants and risperidone were given 60 and 30 min before the test, respectively. The social interaction of male Wistar rats was measured for 10 min, starting 4 h after MK-801 (0.1 mg/kg) administration. In the social interaction test, MK-801-induced deficits in the parameters studied, i.e. the number of episodes and the time of interactions. Risperidone at a higher dose (0.1 mg/kg) reversed that effect. Co-treatment with an ineffective dose of risperidone (0.01 mg/kg) and mirtazapine (2.5 or 5 mg/kg) or escitalopram only at a dose of 5 mg/kg (but not 2.5 and 10 mg/kg) abolished the deficits evoked by MK-801. The obtained results suggest that especially mirtazapine, and to a smaller degree escitalopram may enhance the antipsychotic-like effect of risperidone in the animal test modeling some negative symptoms of schizophrenia. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Allopregnanolone suppresses diabetes-induced neuropathic pain and motor deficit through inhibition of GABAA receptor down-regulation in the spinal cord of diabetic rats

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Samira Afrazi

2014-05-01

Full Text Available Objective(s:Painful diabetic neuropathy is associated with hyperexcitability and hyperactivity of spinal cord neurons. However, its underlying pathophysiological mechanisms have not been fully clarified. Induction of excitatory/inhibitory neurotransmission imbalance at the spinal cord seems to account for the abnormal neuronal activity in diabetes. Protective properties of neurosteroids have been demonstrated in numerous cellular and animal models of neurodegeneration. Materials and Methods: Here, the protective effects of allopregnanolone, a neurosteroid were investigated in an in vivo model of diabetic neuropathy. The tail-flick test was used to assess the nociceptive threshold. Diabetes was induced by injection of 50 mg/kg (IP streptozotocin. Seven weeks after the induction of diabetes, the dorsal half of the lumbar spinal cord was assayed for the expression of γ2 subunit of GABAA receptor using semiquantitative RT-PCR. Results: The data shows that allopregnanolone (5 and 20 mg/kg markedly ameliorated diabetes-induced thermal hyperalgesia and motor deficit. The weights of diabetic rats that received 5 and 20 mg/kg allopregnanolone did not significantly reduce during the time course of study. Furthermore, this neurosteroid could inhibit GABAA receptor down-regulation induced by diabetes in the rat spinal cord. Conclusion: The data revealed that allopregnanolone has preventive effects against hyperglycemic-induced neuropathic pain and motor deficit which are related to the inhibition of GABAA receptor down-regulation.

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.

Technology as a Vehicle for Inclusion of Learners with Attention Deficits in Mainstream Schools

DEFF Research Database (Denmark)

Voldborg, Hanne; Sorensen, Elsebeth Korsgaard

2016-01-01

The potential of technology for supporting educational processes of participation, collaboration and creation is widely accepted. Likewise have digital tools proved to enhance learning processes for disabled learners (e.g. supporting dyslexia students with digital tools such as text-to-speakprogr......The potential of technology for supporting educational processes of participation, collaboration and creation is widely accepted. Likewise have digital tools proved to enhance learning processes for disabled learners (e.g. supporting dyslexia students with digital tools such as text......-to-speakprograms or writing-support programs). A currently topical group, politically and educationally, in the discourse of inclusion is learners with extensive developmental and attention deficit disorders (e.g. Attention Deficit Hyperactivity Disorder (ADHD), Attention Deficit Disorder (ADD), Autism Spectrum Disorder (ASD......), Autism etc.). This paper investigates the potential of technology for supporting the inclusion of this group in the general school system, i.e. into mainstream classes, using technology as a tool to join, participate and contribute – and as a vehicle for general human growth in their learning community...

Adolescent changes in dopamine D1 receptor expression in orbitofrontal cortex and piriform cortex accompany an associative learning deficit.

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Anna K Garske

Full Text Available The orbitofrontal cortex (OFC and piriform cortex are involved in encoding the predictive value of olfactory stimuli in rats, and neural responses to olfactory stimuli in these areas change as associations are learned. This experience-dependent plasticity mirrors task-related changes previously observed in mesocortical dopamine neurons, which have been implicated in learning the predictive value of cues. Although forms of associative learning can be found at all ages, cortical dopamine projections do not mature until after postnatal day 35 in the rat. We hypothesized that these changes in dopamine circuitry during the juvenile and adolescent periods would result in age-dependent differences in learning the predictive value of environmental cues. Using an odor-guided associative learning task, we found that adolescent rats learn the association between an odor and a palatable reward significantly more slowly than either juvenile or adult rats. Further, adolescent rats displayed greater distractibility during the task than either juvenile or adult rats. Using real-time quantitative PCR and immunohistochemical methods, we observed that the behavioral deficit in adolescence coincides with a significant increase in D1 dopamine receptor expression compared to juvenile rats in both the OFC and piriform cortex. Further, we found that both the slower learning and increased distractibility exhibited in adolescence could be alleviated by experience with the association task as a juvenile, or by an acute administration of a low dose of either the dopamine D1 receptor agonist SKF-38393 or the D2 receptor antagonist eticlopride. These results suggest that dopaminergic modulation of cortical function may be important for learning the predictive value of environmental stimuli, and that developmental changes in cortical dopaminergic circuitry may underlie age-related differences in associative learning.

Contextual Learning Induces Dendritic Spine Clustering in Retrosplenial Cortex

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Adam C Frank

2014-03-01

Full Text Available Molecular and electrophysiological studies find convergent evidence suggesting that plasticity within a dendritic tree is not randomly dispersed, but rather clustered into functional groups. Further, results from in silico neuronal modeling show that clustered plasticity is able to increase storage capacity 45 times compared to dispersed plasticity. Recent in vivo work utilizing chronic 2-photon microscopy tested the clustering hypothesis and showed that repetitive motor learning is able to induce clustered addition of new dendritic spines on apical dendrites of L5 neurons in primary motor cortex; moreover, clustered spines were found to be more stable than non-clustered spines, suggesting a physiological role for spine clustering. To further test this hypothesis we used in vivo 2-photon imaging in Thy1-YFP-H mice to chronically examine dendritic spine dynamics in retrosplenial cortex (RSC during spatial learning. RSC is a key component of an extended spatial learning and memory circuit that includes hippocampus and entorhinal cortex. Importantly, RSC is known from both lesion and immediate early gene studies to be critically involved in spatial learning and more specifically in contextual fear conditioning. We utilized a modified contextual fear conditioning protocol wherein animals received a mild foot shock each day for five days; this protocol induces gradual increases in context freezing over several days before the animals reach a behavioral plateau. We coupled behavioral training with four separate in vivo imaging sessions, two before training begins, one early in training, and a final session after training is complete. This allowed us to image spine dynamics before training as well as early in learning and after animals had reached behavioral asymptote. We find that this contextual learning protocol induces a statistically significant increase in the formation of clusters of new dendritic spines in trained animals when compared to home

Effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits in the hippocampus of streptozotocin-induced type 1 diabetes mellitus rats.

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Zhang, Songyun; Li, Hongyan; Zhang, Lihui; Li, Jie; Wang, Ruiying; Wang, Mian

2017-02-15

Increasing evidence demonstrates an association between diabetes and hippocampal neuron damage. This study aimed to determine the effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits (GCLM and GCLC) in the hippocampus of streptozotocin-induced type 1 diabetes mellitus (T1DM) rats. At 12weeks after streptozotocin injection, T1DM rats were randomly divided into 4 groups (n=15 each group) to receive no treatment (T1DM), saline (T1DM+saline), alpha-lipoic acid (T1DM+alpha-lipoic acid), and troxerutin (T1DM+troxerutin), respectively, for 6weeks. Meanwhile, 10 control animals (NC group) were assessed in parallel. Learning performance was evaluated by the Morris water maze. After treatment, hippocampi were collected for pathological examination by hematoxylin and eosin (H&E) staining. Next, hippocampal superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and glutathione (GSH) levels were assessed. Finally, glutamate cysteine ligase catalytic (GCLC) and glutamate cysteine ligase modifier (GCLM) subunit mRNA and protein levels were quantified by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. Compared with T1DM and T1DM+saline groups, escape latency was overtly reduced in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. Significantly increased GCLM and GCLC mRNA levels, GCLC protein amounts, SOD activity, and GSH levels, and reduced MDA amounts were observed in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. In T1DM and T1DM+saline groups, H&E staining showed less pyramidal cells in the hippocampus, with disorganized layers, karyopyknosis, decreased endochylema, and cavitation, effects relieved in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. Troxerutin alleviates oxidative stress and promotes learning in streptozotocin-induced T1DM rats, a process involving GCLC expression. Copyright © 2016 Elsevier B.V. All rights reserved.

Decision-making deficits in patients with chronic schizophrenia: Iowa Gambling Task and Prospect Valence Learning model

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Kim MS

2016-04-01

Full Text Available Myung-Sun Kim,1 Bit-Na Kang,1 Jae Young Lim2 1Department of Psychology, Sungshin Women’s University, Seoul, Republic of Korea; 2Department of Psychiatry, Keyo Medical Foundation, Keyo Hospital, Uiwang, Republic of Korea Purpose: Decision-making is the process of forming preferences for possible options, selecting and executing actions, and evaluating the outcome. This study used the Iowa Gambling Task (IGT and the Prospect Valence Learning (PVL model to investigate deficits in risk-reward related decision-making in patients with chronic schizophrenia, and to identify decision-making processes that contribute to poor IGT performance in these patients. Materials and methods: Thirty-nine patients with schizophrenia and 31 healthy controls participated. Decision-making was measured by total net score, block net scores, and the total number of cards selected from each deck of the IGT. PVL parameters were estimated with the Markov chain Monte Carlo sampling scheme in OpenBugs and BRugs, its interface to R, and the estimated parameters were analyzed with the Mann–Whitney U-test.Results: The schizophrenia group received significantly lower total net scores compared to the control group. In terms of block net scores, an interaction effect of group × block was observed. The block net scores of the schizophrenia group did not differ across the five blocks, whereas those of the control group increased as the blocks progressed. The schizophrenia group obtained significantly lower block net scores in the fourth and fifth blocks of the IGT and selected cards from deck D (advantageous less frequently than the control group. Additionally, the schizophrenia group had significantly lower values on the utility-shape, loss-aversion, recency, and consistency parameters of the PVL model. Conclusion: These results indicate that patients with schizophrenia experience deficits in decision-making, possibly due to failure in learning the expected value of each deck

PMC-12, a Prescription of Traditional Korean Medicine, Improves Amyloid β-Induced Cognitive Deficits through Modulation of Neuroinflammation

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Min Young Park

2015-01-01

Full Text Available PMC-12 is a prescription used in traditional Korean medicine that consists of a mixture of four herbal medicines, Polygonum multiflorum, Rehmannia glutinosa, Polygala tenuifolia, and Acorus gramineus, which have been reported to have various pharmacological effects on age-related neurological diseases. In the present study, we investigated whether PMC-12 improves cognitive deficits associated with decreased neuroinflammation in an amyloid-β-(Aβ- induced mouse model and exerts the antineuroinflammatory effects in lipopolysaccharide-(LPS- stimulated murine BV2 microglia. Intracerebroventricular injection of Aβ25-35 in mice resulted in impairment in learning and spatial memory, whereas this was reversed by oral administration of PMC-12 (100 and 500 mg/kg/day in dose-dependent manners. Moreover, PMC-12 reduced the increase of Aβ expression and activation of microglia and astrocytes in the Aβ25-35-injected brain. Furthermore, quantitative PCR data showed that inflammatory mediators were significantly decreased by administration of PMC-12 in Aβ-injected brains. Consistent with the in vivo data, PMC-12 significantly reduced the inflammatory mediators in LPS-stimulated BV2 cells without cell toxicity. Moreover, PMC-12 exhibited anti-inflammatory properties via downregulation of ERK, JNK, and p38 MAPK pathways. These findings suggest that the protective effects of PMC-12 may be mediated by its antineuroinflammatory activities, resulting in the attenuation of memory impairment; accordingly, PMC-12 may be useful in the prevention and treatment of AD.

Neurocognitive impairment in deficit and non-deficit schizophrenia: a meta-analysis.

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Bora, E; Binnur Akdede, B; Alptekin, K

2017-10-01

Most studies suggested that patients with deficit schizophrenia have more severe impairment compared with patients with non-deficit schizophrenia. However, it is not clear whether deficit and non-deficit schizophrenia are associated with differential neurocognitive profiles. The aim of this meta-analytic review was to compare cognitive performances of deficit and non-deficit patients with each other and with healthy controls. In the current meta-analysis, differences in cognitive abilities between 897 deficit and 1636 non-deficit patients with schizophrenia were examined. Cognitive performances of 899 healthy controls were also compared with 350 patients with deficit and 592 non-deficit schizophrenia. Both deficit (d = 1.04-1.53) and non-deficit (d = 0.68-1.19) schizophrenia were associated with significant deficits in all cognitive domains. Deficit patients underperformed non-deficit patients in all cognitive domains (d = 0.24-0.84) and individual tasks (d = 0.39-0.93). The relationship between deficit syndrome and impairment in olfaction, social cognition, verbal fluency, and speed-based cognitive tasks were relatively stronger. Our findings suggest that there is consistent evidence for a significant relationship between deficit syndrome and more severe cognitive impairment in schizophrenia.

Organophosphate-Induced Changes in the PKA Regulatory Function of Swiss Cheese/NTE Lead to Behavioral Deficits and Neurodegeneration

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Kretzschmar, Doris

2014-01-01

Organophosphate-induced delayed neuropathy (OPIDN) is a Wallerian-type axonopathy that occurs weeks after exposure to certain organophosphates (OPs). OPs have been shown to bind to Neuropathy Target Esterase (NTE), thereby inhibiting its enzymatic activity. However, only OPs that also induce the so-called aging reaction cause OPIDN. This reaction results in the release and possible transfer of a side group from the bound OP to NTE and it has been suggested that this induces an unknown toxic function of NTE. To further investigate the mechanisms of aging OPs, we used Drosophila, which expresses a functionally conserved orthologue of NTE named Swiss Cheese (SWS). Treating flies with the organophosporous compound tri-ortho-cresyl phosphate (TOCP) resulted in behavioral deficits and neurodegeneration two weeks after exposure, symptoms similar to the delayed effects observed in other models. In addition, we found that primary neurons showed signs of axonal degeneration within an hour after treatment. Surprisingly, increasing the levels of SWS, and thereby its enzymatic activity after exposure, did not ameliorate these phenotypes. In contrast, reducing SWS levels protected from TOCP-induced degeneration and behavioral deficits but did not affect the axonopathy observed in cell culture. Besides its enzymatic activity as a phospholipase, SWS also acts as regulatory PKA subunit, binding and inhibiting the C3 catalytic subunit. Measuring PKA activity in TOCP treated flies revealed a significant decrease that was also confirmed in treated rat hippocampal neurons. Flies expressing additional PKA-C3 were protected from the behavioral and degenerative phenotypes caused by TOCP exposure whereas primary neurons were not. In addition, knocking-down PKA-C3 caused similar behavioral and degenerative phenotypes as TOCP treatment. We therefore propose a model in which OP-modified SWS cannot release PKA-C3 and that the resulting loss of PKA-C3 activity plays a crucial role in developing

Impact of executive function deficits and attention-deficit/hyperactivity disorder (ADHD) on academic outcomes in children.

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Biederman, Joseph; Monuteaux, Michael C; Doyle, Alysa E; Seidman, Larry J; Wilens, Timothy E; Ferrero, Frances; Morgan, Christie L; Faraone, Stephen V

2004-10-01

The association between executive function deficits (EFDs) and functional outcomes were examined among children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Participants were children and adolescents with (n = 259) and without (n = 222) ADHD, as ascertained from pediatric and psychiatric clinics. The authors defined EFD as at least 2 executive function measures impaired. Significantly more children and adolescents with ADHD had EFDs than did control participants. ADHD with EFDs was associated with an increased risk for grade retention and a decrease in academic achievement relative to (a) ADHD alone, (b) controlled socioeconomic status, (c) learning disabilities, and (d) IQ. No differences were noted in social functioning or psychiatric comorbidity. Children and adolescents with ADHD and EFDs were found to be at high risk for significant impairments in academic functioning. These results support screening children with ADHD for EFDs to prevent academic failure.

Potential Association of Lead Exposure During Early Development of Mice With Alteration of Hippocampus Nitric Oxide Levels and Learning Memory

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LI SUN; ZHENG-YAN ZHAO; JIAN HU; XIE-LAI ZHOU

2005-01-01

Objective Chronic lead (Pb) exposure during development is known to produce learning deficits. Nitric oxide participates in the synaptic mechanisms involved in certain forms of learning and memory. This study was designed to clarify whether Pb-induced impairment in learning and memory was associated with the changes of nitric oxide levels in mice brains.Methods Sixty Balb/c mice aged 10 days were chosen. A model of lead exposure was established by drinking 0.025%, 0.05%,0.075% lead acetate, respectively for 8 weeks. The controls were orally given distilled water. The ability to learn and memorize was examined by open field test, T-water maze test. In parallel with the behavioral data, NO level of hippocampus tissue was detected by biochemical assay. Results Compared with control groups, (1) the weight of 0.075% group was significantly reduced (P＜0.05); (2) The number of times in mice attaining the required standards in T-water maze test was lower in 0.075%group (P＜0.01). No significant difference was found between experimental and control groups in open field test (P＞0.05); (3)NO level of mouse hippocampus tissue was decreased in 0.075% group (P＜0.01). Conclusions The findings suggest that decreased hippocampus NO level may contribute to the Pb-induced deficits in learning and memory processes.

Deficits in memory and visuospatial learning correlate with regional hippocampal atrophy in MS.

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Longoni, Giulia; Rocca, Maria A; Pagani, Elisabetta; Riccitelli, Gianna C; Colombo, Bruno; Rodegher, Mariaemma; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

2015-01-01

The hippocampus has a critical role in episodic memory and visuospatial learning and consolidation. We assessed the patterns of whole and regional hippocampal atrophy in a large group of multiple sclerosis (MS) patients, and their correlations with neuropsychological impairment. From 103 MS patients and 28 healthy controls (HC), brain dual-echo and high-resolution 3D T1-weighted images were acquired using a 3.0-Tesla scanner. All patients underwent a neuropsychological assessment of hippocampal-related cognitive functions, including Paired Associate Word Learning, Short Story, delayed recall of Rey-Osterrieth Complex Figure and Paced Auditory Serial Attention tests. The hippocampi were manually segmented and volumes derived. Regional atrophy distribution was assessed using a radial mapping analysis. Correlations between hippocampal atrophy and clinical, neuropsychological and MRI metrics were also evaluated. Hippocampal volume was reduced in MS patients vs HC (p right and hippocampus). In MS patients, radial atrophy affected CA1 subfield and subiculum of posterior hippocampus, bilaterally. The dentate hilus (DG:H) of the right hippocampal head was also affected. Regional hippocampal atrophy correlated with brain T2 and T1 lesion volumes, while no correlation was found with disability. Damage to the CA1 and subiculum was significantly correlated to the performances at hippocampal-targeted neuropsychological tests. These results show that hippocampal subregions have a different vulnerability to MS-related damage, with a relative sparing of the head of the left hippocampus. The assessment of regional hippocampal atrophy may help explain deficits of specific cognitive functions in MS patients, including memory and visuospatial abilities.

Embryological exposure to valproic acid induces social interaction deficits in zebrafish (Danio rerio): A developmental behavior analysis.

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Zimmermann, Fernanda Francine; Gaspary, Karina Vidarte; Leite, Carlos Eduardo; De Paula Cognato, Giana; Bonan, Carla Denise

2015-01-01

Changes in social behavior are associated with brain disorders, including mood disorders, stress, schizophrenia, Alzheimer's disease, and autism spectrum disorders (ASD). Autism is a complex neurodevelopmental disorder characterized by deficits in social interaction, impaired communication, anxiety, hyperactivity, and the presence of restricted interests. Zebrafish is one of the most social vertebrates used as a model in biomedical research, contributing to an understanding of the mechanisms that underlie social behavior. Valproic acid (VPA) is used as an anti-epileptic drug and mood stabilizer; however, prenatal VPA exposure in humans has been associated with an increased incidence of autism and it can also affect fetal brain development. Therefore, we conducted a behavioral screening at different periods of zebrafish development at 6, 30, 70, and 120dpf (days postfertilization) after VPA exposure in the early development stage to investigate social behavior, locomotion, aggression, and anxiety. VPA (48μM) exposure during the first 48hpf (hours postfertilization) did not promote changes on survival, morphology, and hatching rate at 24hpf, 48hpf, and 72hpf. The behavioral patterns suggest that VPA exposure induces changes in locomotor activity and anxiety at different developmental periods in zebrafish. Furthermore, a social interaction deficit is present at 70dpf and 120dpf. VPA exposure did not affect aggression in the adult stage at 70dpf and 120dpf. This is the first study that demonstrated zebrafish exposed to VPA during the first 48h of development exhibit deficits in social interaction, anxiety, and hyperactivity at different developmental periods. Copyright © 2015 Elsevier Inc. All rights reserved.

Addressing Nature Deficit Disorder through Primitive Camping Experiences

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Allen, Kevin; Varner, Keegan; Sallee, Jeff

2011-01-01

Today's youth suffer from Nature Deficit Disorder, a condition that has been connected to ADHD, shortage of creativity, and general lack of knowledge about the outdoors. A team of educators and specialists are addressing this issue with primitive camping. County educators were trained using experiential learning and train-the-trainer techniques.…

Impairment of the spatial learning and memory induced by learned helplessness and chronic mild stress.

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Song, Li; Che, Wang; Min-Wei, Wang; Murakami, Yukihisa; Matsumoto, Kinzo

2006-02-01

Increasing evidences indicate the concurrence and interrelationship of depression and cognitive impairments. The present study was undertaken to investigate the effects of two depressive animal models, learned helplessness (LH) and chronic mild stress (CMS), on the cognitive functions of mice in the Morris water maze task. Our results demonstrated that both LH and CMS significantly decreased the cognitive performance of stressed mice in the water maze task. The escaping latency to the platform was prolonged and the probe test percentage in the platform quadrant was reduced. These two models also increased the plasma corticosterone concentration and decreased the brain derived neurotrophic factor (BDNF) and cAMP-response element-biding protein (CREB) messenger ribonucleic acid (mRNA) levels in hippocampus, which might cause the spatial cognition deficits. Repeated treatment with antidepressant drugs, imipramine (Imi) and fluoxetine (Flu), significantly reduced the plasma corticosterone concentration and enhanced the BDNF and CREB levels. Furthermore, antidepressant treated animals showed an ameliorated cognitive performance compared with the vehicle treated stressed animals. These data suggest that both LH and CMS impair the spatial cognitive function and repeated treatment with antidepressant drugs decreases the prevalence of cognitive impairments induced by these two animal models. Those might in part be attributed to the reduced plasma corticosterone and enhanced hippocampal BDNF and CREB expressions. This study provided a better understanding of molecular mechanisms underlying interactions of depression and cognitive impairments, although animal models used in this study can mimic only some aspects of depression or cognition of human.

Red sorrel (Hibiscus Sabdariffa) prevents the ethanol-induced deficits of Purkinje cells in the cerebellum.

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Suryanti, S; Partadiredja, G; Atthobari, J

2015-01-01

The present study is aimed at investigating the possible protective effects of H. sabdariffa on ethanol-elicited deficits of motor coordination and estimated total number of the Purkinje cells of the cerebellums of adolescent male Wistar rats. Forty male Wistar rats aged 21 days were divided into five groups. Na/wtr group was given water orally and injected with normal saline intra peritoneally (ip). Eth/wtr group was given water orally and ethanol (ip). Another three experimental groups (Eth/Hsab) were given different dosages of H. sabdariffa and ethanol (ip). All groups were treated intermittently for the total period of treatment of two weeks. The motor coordination of rats was tested prior and subsequent to the treatments. The rats were euthanized, and their cerebellums were examined. The total number of Purkinje cells was estimated using physical fractionator method. Upon revolving drum test, the number of falls of rats increased following ethanol treatment. There was no significant difference between the total number of falls prior and subsequent to treatment in all Eth/Hsab groups. The estimated total number of Purkinje cells in Eth/Hsab groups was higher than in Eth/wtr group. H. sabdariffa may prevent the ethanol-induced deficits of motor coordination and estimated total number of Purkinje cells of the cerebellums in adolescent rats (Tab. 3, Fig. 1, Ref. 42).

The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts delay-dependent and scopolamine-induced recognition memory deficits in rats.

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Pitsikas, Nikolaos; Gravanis, Achille

2017-04-01

Experimental evidence indicates that the neurosteroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) are involved in cognition. BNN27 is a novel 17C spiroepoxy-DHEA derivative, which devoid of steroidogenic activity. The neuroprotective effects of BNN27 have been recently reported. The present study was designed to investigate the effects of BNN27 on recognition memory in rats. For this purpose, the novel object task (NOT), a procedure assessing non-spatial recognition memory and the novel location task (NLT), a procedure evaluating spatial recognition memory were used. Intraperitoneal (i.p.) administration of BNN27 (3 and 10mg/kg) antagonized delay-dependent deficits in the NOT in the normal rat, suggesting that this DHEA derivative affected acquisition, storage and retrieval of information. In addition, BNN27 (3 and 10mg/kg, i.p.) counteracted the scopolamine [0.2mg/kg, subcutaneously (s.c.)]-induced non-spatial and spatial recognition memory deficits. These findings suggest that BNN27 may modulate different aspects of recognition memory, potentially interacting with the cholinergic system, relevant to cognition. Copyright © 2017 Elsevier Inc. All rights reserved.

Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism.

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Hara, Yuta; Ago, Yukio; Higuchi, Momoko; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

2017-11-01

Recent studies have reported that oxytocin ameliorates behavioral abnormalities in both animal models and individuals with autism spectrum disorders (ASD). However, the mechanisms underlying the ameliorating effects of oxytocin remain unclear. In this study, we examined the effects of intranasal oxytocin on impairments in social interaction and recognition memory in an ASD mouse model in which animals are prenatally exposed to valproic acid (VPA). We found that a single intranasal administration of oxytocin restored social interaction deficits for up to 2h in mice prenatally exposed to VPA, but there was no effect on recognition memory impairments. Additionally, administration of oxytocin across 2weeks improved prenatal VPA-induced social interaction deficits for at least 24h. In contrast, there were no effects on the time spent sniffing in control mice. Immunohistochemical analysis revealed that intranasal administration of oxytocin increased c-Fos expression in the paraventricular nuclei (PVN), prefrontal cortex, and somatosensory cortex, but not the hippocampal CA1 and CA3 regions of VPA-exposed mice, suggesting the former regions may underlie the effects of oxytocin. These findings suggest that oxytocin attenuates social interaction deficits through the activation of higher cortical areas and the PVN in an ASD mouse model. Copyright © 2017 Elsevier Inc. All rights reserved.

Vascular Risk Factors and Diseases Modulate Deficits of Reward-Based Reversal Learning in Acute Basal Ganglia Stroke.

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Ulla K Seidel

Full Text Available Besides motor function, the basal ganglia have been implicated in feedback learning. In patients with chronic basal ganglia infarcts, deficits in reward-based reversal learning have previously been described.We re-examined the acquisition and reversal of stimulus-stimulus-reward associations and acquired equivalence in eleven patients with acute basal ganglia stroke (8 men, 3 women; 57.8±13.3 years, whose performance was compared eleven healthy subjects of comparable age, sex distribution and education, who were recruited outside the hospital. Eleven hospitalized patients with a similar vascular risk profile as the stroke patients but without stroke history served as clinical control group.In a neuropsychological assessment 7±3 days post-stroke, verbal and spatial short-term and working memory and inhibition control did not differ between groups. Compared with healthy subjects, control patients with vascular risk factors exhibited significantly reduced performance in the reversal phase (F[2,30] = 3.47; p = 0.044; post-hoc comparison between risk factor controls and healthy controls: p = 0.030, but not the acquisition phase (F[2,30] = 1.01; p = 0.376 and the acquired equivalence (F[2,30] = 1.04; p = 0.367 tasks. In all tasks, the performance of vascular risk factor patients closely resembled that of basal ganglia stroke patients. Correlation studies revealed a significant association of the number of vascular risk factors with reversal learning (r = -0.33, p = 0.012, but not acquisition learning (r = -0.20, p = 0.121 or acquired equivalence (r = -0.22, p = 0.096.The previously reported impairment of reward-based learning may be attributed to vascular risk factors and associated diseases, which are enriched in stroke patients. This study emphasizes the necessity of appropriate control subjects in cognition studies.

HIV-infected persons with bipolar disorder are less aware of memory deficits than HIV-infected persons without bipolar disorder

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Blackstone, K; Tobin, A; Posada, C; Gouaux, B; Grant, I; Moore, DJ

2012-01-01

Episodic memory deficits are common in HIV infection and bipolar disorder, but patient insight into such deficits remains unclear. Thirty-four HIV-infected individuals without bipolar disorder (HIV+/BD-) and 47 HIV+ individuals with comorbid bipolar disorder (HIV+/BD+) were administered the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised to examine objective learning/memory functioning. Subjective memory complaints were assessed via the memory s ubscale of ...

Experimental Training of Children with Attention Deficit/Hyperactivity Disorder

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Piscalkiene, Viktorija

2009-01-01

Attention-deficit/hyperactivity disorder (AD/HD) negatively affects the cognitive and psychomotoric spheres of the pupil's social behavior and social adaptation. The review of many studies states that pupils with AD/HD achieve worse learning results because of insufficiently functioning cognitive processes, such as attention, (work) memory,…

Effects of cariprazine, a novel antipsychotic, on cognitive deficit and negative symptoms in a rodent model of schizophrenia symptomatology.

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Neill, Jo C; Grayson, Ben; Kiss, Béla; Gyertyán, István; Ferguson, Paul; Adham, Nika

2016-01-01

Negative symptoms and cognitive impairment associated with schizophrenia are strongly associated with poor functional outcome and reduced quality of life and remain an unmet clinical need. Cariprazine is a dopamine D3/D2 receptor partial agonist with preferential binding to D3 receptors, recently approved by the FDA for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder. The aim of this study is to evaluate effects of cariprazine in an animal model of cognitive deficit and negative symptoms of schizophrenia. Following sub-chronic PCP administration (2mg/kg, IP for 7 days followed by 7 days drug-free), female Lister Hooded rats were administered cariprazine (0.05, 0.1, or 0.25mg/kg, PO) or risperidone (0.16 or 0.1mg/kg, IP) before testing in novel object recognition (NOR), reversal learning (RL), and social interaction (SI) paradigms. As we have consistently demonstrated, sub-chronic PCP significantly impaired behavior in these tests. Deficits were significantly improved by cariprazine, in a dose dependent manner in the operant RL test with efficacy at lower doses in the NOR and SI tests. Locomotor activity was reduced at the highest doses of 0.1mg/kg and 0.25mg/kg in NOR and SI. Risperidone also reversed the PCP-induced deficit in all tests. In conclusion, cariprazine was effective to overcome PCP-induced deficits in cognition and social behavior in a thoroughly validated rat model in tests representing specific symptom domains in schizophrenia patients. These findings support very recent results showing efficacy of cariprazine in the treatment of negative symptoms in schizophrenia patients. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Quantitative EEG neurofeedback for the treatment of pediatric attention-deficit/hyperactivity disorder, autism spectrum disorders, learning disorders, and epilepsy.

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Hurt, Elizabeth; Arnold, L Eugene; Lofthouse, Nicholas

2014-07-01

Neurofeedback (NF) using surface electroencephalographic signals has been used to treat various child psychiatric disorders by providing patients with video/audio information about their brain's electrical activity in real-time. Research data are reviewed and clinical recommendations are made regarding NF treatment of youth with attention deficit/hyperactivity disorder, autism, learning disorders, and epilepsy. Most NF studies are limited by methodological issues, such as failure to use or test the validity of a full-blind or sham NF. The safety of NF treatment has not been thoroughly investigated in youth or adults, although clinical experience suggests reasonable safety. Copyright © 2014 Elsevier Inc. All rights reserved.

Cognitive deficits and educational loss in children with schistosome infection-A systematic review and meta-analysis.

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Ezeamama, Amara E; Bustinduy, Amaya L; Nkwata, Allan K; Martinez, Leonardo; Pabalan, Noel; Boivin, Michael J; King, Charles H

2018-01-01

By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains-learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5-19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in

Cognitive deficits and educational loss in children with schistosome infection-A systematic review and meta-analysis.

Directory of Open Access Journals (Sweden)

Amara E Ezeamama

2018-01-01

Full Text Available By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC is associated with educational loss and cognitive deficits.This review was prospectively registered in the PROSPERO database (CRD42016040052. Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains-learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD and 95% confidence intervals (CI were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5-19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12, scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20, learning (SMD = -0.39, 95%CI: -0.70, -0.09 and memory (SMD = -0.28, 95%CI: -0.52, -0.04 tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30 and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06. Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits

Cognitive deficits and educational loss in children with schistosome infection—A systematic review and meta-analysis

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Bustinduy, Amaya L.; Nkwata, Allan K.; Martinez, Leonardo; Pabalan, Noel; Boivin, Michael J.; King, Charles H.

2018-01-01

Background By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. Methodology/Principal findings This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains—learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5–19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The

Neurofeedback as an Intervention to Improve Reading Achievement in Students with Attention- Deficit/Hyperactivity Disorder, Inattentive Subtype

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La Marca, Jeffry P.; O'Connor, Rollanda E.

2016-01-01

Research consistently demonstrates that attention deficits have a deleterious effect on academic achievement. Impairments in attention, and not hyperactivity/impulsivity, are associated with learning difficulties and academic problems in students with attention-deficit/hyperactivity disorder (ADHD). To date, most studies have focused on symptoms…

Role of the medial prefrontal cortex in impaired decision making in juvenile attention-deficit/hyperactivity disorder.

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Hauser, Tobias U; Iannaccone, Reto; Ball, Juliane; Mathys, Christoph; Brandeis, Daniel; Walitza, Susanne; Brem, Silvia

2014-10-01

Attention-deficit/hyperactivity disorder (ADHD) has been associated with deficient decision making and learning. Models of ADHD have suggested that these deficits could be caused by impaired reward prediction errors (RPEs). Reward prediction errors are signals that indicate violations of expectations and are known to be encoded by the dopaminergic system. However, the precise learning and decision-making deficits and their neurobiological correlates in ADHD are not well known. To determine the impaired decision-making and learning mechanisms in juvenile ADHD using advanced computational models, as well as the related neural RPE processes using multimodal neuroimaging. Twenty adolescents with ADHD and 20 healthy adolescents serving as controls (aged 12-16 years) were examined using a probabilistic reversal learning task while simultaneous functional magnetic resonance imaging and electroencephalogram were recorded. Learning and decision making were investigated by contrasting a hierarchical Bayesian model with an advanced reinforcement learning model and by comparing the model parameters. The neural correlates of RPEs were studied in functional magnetic resonance imaging and electroencephalogram. Adolescents with ADHD showed more simplistic learning as reflected by the reinforcement learning model (exceedance probability, Px = .92) and had increased exploratory behavior compared with healthy controls (mean [SD] decision steepness parameter β: ADHD, 4.83 [2.97]; controls, 6.04 [2.53]; P = .02). The functional magnetic resonance imaging analysis revealed impaired RPE processing in the medial prefrontal cortex during cue as well as during outcome presentation (P decision making and learning mechanisms in adolescents with ADHD are driven by impaired RPE processing in the medial prefrontal cortex. This novel, combined approach furthers the understanding of the pathomechanisms in ADHD and may advance treatment strategies.

Learning of Grammar-Like Visual Sequences by Adults with and without Language-Learning Disabilities

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Aguilar, Jessica M.; Plante, Elena

2014-01-01

Purpose: Two studies examined learning of grammar-like visual sequences to determine whether a general deficit in statistical learning characterizes this population. Furthermore, we tested the hypothesis that difficulty in sustaining attention during the learning task might account for differences in statistical learning. Method: In Study 1,…

Memory Deficits in Learning Disabled.

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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…

The effects of the selective 5-HT(2C) receptor antagonist SB 242084 on learned helplessness in male Fischer 344 rats.

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Strong, Paul V; Greenwood, Benjamin N; Fleshner, Monika

2009-05-01

Rats exposed to an uncontrollable stressor demonstrate a constellation of behaviors such as exaggerated freezing and deficits in shuttle box escape learning. These behaviors in rats have been called learned helplessness and have been argued to model human stress-related mood disorders. Learned helplessness is thought to be caused by hyperactivation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) and a subsequent exaggerated release of 5-HT in DRN projection sites. Blocking 5-HT(2C) receptors in the face of an increase in serotonin can alleviate anxiety behaviors in some animal models. However, specific 5-HT receptor subtypes involved in learned helplessness remain unknown. The current experiments tested the hypothesis that 5-HT(2C) receptor activation is necessary and sufficient for the expression of learned helplessness. The selective 5-HT(2C) receptor antagonist SB 242084 (1.0 mg/kg) administered i.p. to adult male Fischer 344 rats prior to shuttle box behavioral testing, but not before stress, blocked stress-induced deficits in escape learning but had no effect on the exaggerated shock-elicited freezing. The selective 5-HT(2C) receptor agonist CP-809101 was sufficient to produce learned helplessness-like behaviors in the absence of prior stress and these effects were blocked by pretreatment with SB 242084. Results implicate the 5-HT(2C) receptor subtype in mediating the shuttle box escape deficits produced by exposure to uncontrollable stress and suggest that different postsynaptic 5-HT receptor subtypes underlie the different learned helplessness behaviors.

Differentiating children with attention-deficit/hyperactivity disorder, conduct disorder, learning disabilities and autistic spectrum disorders by means of their motor behavior characteristics.

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Efstratopoulou, Maria; Janssen, Rianne; Simons, Johan

2012-01-01

The study was designed to investigate the discriminant validity of the Motor Behavior Checklist (MBC) for distinguishing four group of children independently classified with Attention-Deficit/Hyperactivity Disorder, (ADHD; N=22), Conduct Disorder (CD; N=17), Learning Disabilities (LD; N=24) and Autistic Spectrum Disorders (ASD; N=20). Physical education teachers used the MBC for children to rate their pupils based on their motor related behaviors. A multivariate analysis revealed significant differences among the groups on different problem scales. The results indicated that the MBC for children may be effective in discriminating children with similar disruptive behaviors (e.g., ADHD, CD) and autistic disorders, based on their motor behavior characteristics, but not children with Learning Disabilities (LD), when used by physical education teachers in school settings. Copyright © 2011 Elsevier Ltd. All rights reserved.

Basolateral amygdala inactivation impairs learning-induced long-term potentiation in the cerebellar cortex.

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Lan Zhu

Full Text Available Learning to fear dangerous situations requires the participation of basolateral amygdala (BLA. In the present study, we provide evidence that BLA is necessary for the synaptic strengthening occurring during memory formation in the cerebellum in rats. In the cerebellar vermis the parallel fibers (PF to Purkinje cell (PC synapse is potentiated one day following fear learning. Pretraining BLA inactivation impaired such a learning-induced long-term potentiation (LTP. Similarly, cerebellar LTP is affected when BLA is blocked shortly, but not 6 h, after training. The latter result shows that the effects of BLA inactivation on cerebellar plasticity, when present, are specifically related to memory processes and not due to an interference with sensory or motor functions. These data indicate that fear memory induces cerebellar LTP provided that a heterosynaptic input coming from BLA sets the proper local conditions. Therefore, in the cerebellum, learning-induced plasticity is a heterosynaptic phenomenon that requires inputs from other regions. Studies employing the electrically-induced LTP in order to clarify the cellular mechanisms of memory should therefore take into account the inputs arriving from other brain sites, considering them as integrative units. Based on previous and the present findings, we proposed that BLA enables learning-related plasticity to be formed in the cerebellum in order to respond appropriately to new stimuli or situations.

The arcuate fasciculus network and verbal deficits in psychosis

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Kenney Joanne P.M.

2017-11-01

Full Text Available Verbal learning (VL and fluency (VF are prominent cognitive deficits in psychosis, of which the precise neuroanatomical contributions are not fully understood. We investigated the arcuate fasciculus (AF and its associated cortical regions to identify structural abnormalities contributing to these verbal impairments in early stages of psychotic illness.

Long term verbal memory recall deficits in fragile X premutation females.

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Shelton, Annie L; Cornish, Kim; Fielding, Joanne

2017-10-01

Carriers of a FMR1 premutation allele (between 55 and 199 CGG repeats) are at risk of developing a wide range of medical, psychiatric and cognitive disorders, including executive dysfunction. These cognitive deficits are often less severe for female premutation carriers compared to male premutation carriers, albeit similar in nature. However, it remains unclear whether female premutation carriers who exhibit executive dysfunction also report verbal learning and memory deficits like those of their male counterparts. Here we employed the CVLT to assess verbal learning and memory function in 19 female premutation carriers, contrasting performance with 19 age- and IQ-matched controls. Group comparisons revealed similar performance during the learning and short delay recall phases of the CVLT. However, after a long delay period, female premutation carriers remembered fewer words for both free and cued recall trials, but not during recognition trials. These findings are consistent with reports for male premutation carriers, and suggest that aspects of long term memory may be adversely affect in a subgroup of premutation carriers with signs of executive dysfunction. Copyright © 2017. Published by Elsevier Inc.

Diacylglycerol kinase β knockout mice exhibit attention-deficit behavior and an abnormal response on methylphenidate-induced hyperactivity.

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Mitsue Ishisaka

Full Text Available BACKGROUND: Diacylglycerol kinase (DGK is an enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. DGKβ is one of the subtypes of the DGK family and regulates many intracellular signaling pathways in the central nervous system. Previously, we demonstrated that DGKβ knockout (KO mice showed various dysfunctions of higher brain function, such as cognitive impairment (with lower spine density, hyperactivity, reduced anxiety, and careless behavior. In the present study, we conducted further tests on DGKβ KO mice in order to investigate the function of DGKβ in the central nervous system, especially in the pathophysiology of attention deficit hyperactivity disorder (ADHD. METHODOLOGY/PRINCIPAL FINDINGS: DGKβ KO mice showed attention-deficit behavior in the object-based attention test and it was ameliorated by methylphenidate (MPH, 30 mg/kg, i.p.. In the open field test, DGKβ KO mice displayed a decreased response to the locomotor stimulating effects of MPH (30 mg/kg, i.p., but showed a similar response to an N-methyl-d-aspartate (NMDA receptor antagonist, MK-801 (0.3 mg/kg, i.p., when compared to WT mice. Examination of the phosphorylation of extracellular signal-regulated kinase (ERK, which is involved in regulation of locomotor activity, indicated that ERK1/2 activation induced by MPH treatment was defective in the striatum of DGKβ KO mice. CONCLUSIONS/SIGNIFICANCE: These findings suggest that DGKβ KO mice showed attention-deficit and hyperactive phenotype, similar to ADHD. Furthermore, the hyporesponsiveness of DGKβ KO mice to MPH was due to dysregulation of ERK phosphorylation, and that DGKβ has a pivotal involvement in ERK regulation in the striatum.

Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3β decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model.

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Ponce-Lopez, Teresa; Liy-Salmeron, Gustavo; Hong, Enrique; Meneses, Alfredo

2011-12-02

Intracerebroventricular (ICV) streptozotocin (STZ) treated rat has been described as a suitable model for sporadic Alzheimer's disease (AD). Central application of STZ has demonstrated behavioral and neurochemical features that resembled those found in human AD. Chronic treatments with antioxidants, acetylcholinesterase (AChE) inhibitors, or improving glucose utilization drugs have reported a beneficial effect in ICV STZ-treated rats. In the present study the post-training administration of a glycogen synthase kinase (GSK3) inhibitor, lithium; antidementia drugs: phenserine and memantine, and insulin sensitizer, pioglitazone on memory function of ICV STZ-rats was assessed. In these same animals the phosphorylated GSK3β (p-GSK3β) and total GSK3β levels were determined, and importantly GSK3β regulates the tau phosphorylation responsible for neurofibrillary tangle formation in AD. Wistar rats received ICV STZ application (3mg/kg twice) and 2 weeks later short- (STM) and long-term memories (LTM) were assessed in an autoshaping learning task. Animals were sacrificed immediately following the last autoshaping session, their brains removed and dissected. The enzymes were measured in the hippocampus and prefrontal cortex (PFC) by western blot. ICV STZ-treated rats showed a memory deficit and significantly decreased p-GSK3β levels, while total GSK3β did not change, in both the hippocampus and PFC. Memory impairment was reversed by lithium (100mg/kg), phenserine (1mg/kg), memantine (5mg/kg) and pioglitazone (30 mg/kg). The p-GSK3β levels were restored by lithium, phenserine and pioglitazone in the hippocampus, and restored by lithium in the PFC. Memantine produced no changes in p-GSK3β levels in neither the hippocampus nor PFC. Total GSK3β levels did not change with either drug. Altogether these results show the beneficial effects of drugs with different mechanisms of actions on memory impairment induced by ICV STZ, and restored p-GSK3β levels, a kinase key of

Kv4.2 knockout mice display learning and memory deficits in the Lashley maze [version 1; referees: 2 approved

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Gregory D. Smith

2016-10-01

Full Text Available Background: Potassium channels have been shown to be involved in neural plasticity and learning. Kv4.2 is a subunit of the A-type potassium channel. Kv4.2 channels modulate excitability in the dendrites of pyramidal neurons in the cortex and hippocampus. Deletion of Kv4.2 results in spatial learning and conditioned fear deficits; however, previous studies have only examined deletion of Kv4.2 in aversive learning tests. Methods: For the current study, we used the Lashley maze as an appetitive learning test. We examined Kv4.2 wildtype (WT and knockout (KO mice in the Lashley maze over 4 days during adulthood. The first day consisted of habituating the mice to the maze. The mice then received five trials per day for the next 3 days. The number of errors and the time to the goal box was recorded for each trial. The goal box contained a weigh boat with an appetitive reward (gelatin with sugar. There was an intertrial interval of 15 minutes. Results: We found that Kv4.2 KO mice committed more errors across the trials compared to the WT mice p<0.001. There was no difference in the latency to find the goal box over the period. Discussion: Our finding that deletion of Kv4.2 resulted in more errors in the Lashley maze across 15 trials contribute to a growing body of evidence that Kv4.2 channels are significantly involved in learning and memory.

Kv4.2 knockout mice display learning and memory deficits in the Lashley maze [version 2; referees: 2 approved

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Gregory D. Smith

2017-02-01

Full Text Available Background: Potassium channels have been shown to be involved in neural plasticity and learning. Kv4.2 is a subunit of the A-type potassium channel. Kv4.2 channels modulate excitability in the dendrites of pyramidal neurons in the cortex and hippocampus. Deletion of Kv4.2 results in spatial learning and conditioned fear deficits; however, previous studies have only examined deletion of Kv4.2 in aversive learning tests. Methods: For the current study, we used the Lashley maze as an appetitive learning test. We examined Kv4.2 wildtype (WT and knockout (KO mice in the Lashley maze over 4 days during adulthood. The first day consisted of habituating the mice to the maze. The mice then received five trials per day for the next 3 days. The number of errors and the time to the goal box was recorded for each trial. The goal box contained a weigh boat with an appetitive reward (gelatin with sugar. There was an intertrial interval of 15 minutes. Results: We found that Kv4.2 KO mice committed more errors across the trials compared to the WT mice p<0.001. There was no difference in the latency to find the goal box over the period. Discussion: Our finding that deletion of Kv4.2 resulted in more errors in the Lashley maze across 15 trials contribute to a growing body of evidence that Kv4.2 channels are significantly involved in learning and memory.

Physiological and biochemical changes in Matricaria chamomilla induced by Pseudomonas fluorescens and water deficit stress

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Hamid MOHAMMADI

2018-04-01

Full Text Available Environmental stresses and rhizosphere microorganisms affect growth parameters and accumulation of active ingredients especially in plants with medicinal properties. The present study examined the effects of chamomile (Matricaria chamomilla L. seedling inoculation with Pseudomonas fluorescens PF-135 strain on its growth parameters, photosynthetic pigments, proline, malondialdehyde (MDA, and hydrogen peroxide (H2O2 content, and essential oil concentration at both regular watering and water deficit experiments. Based on the obtained results, water deficit stress reduced root dry mass, and flower fresh and dry mass as well. However, amount of H2O2 and MDA in root and shoot tissues were considerably lower in inoculated plants compared to non-inoculated ones under both normal watering and water deficit regimes. It indicates that lipid peroxidation and production of reactive oxygen species has been diminished in inoculated plants. Also, essential oil content in inoculated plants significantly increased compared with that of non-inoculated ones under water deficit stress condition. It can be concluded that P. fluorescens PF-135 strain has an outstanding potential to alleviate adverse effects of water deficit on plant growth, and hence can be used as an excellent PGPR in order to boost chamomile productivity especially under water deficit stress condition.

Children's Use of Self-Paced Slideshows: An Extension of the Video Deficit Effect?

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Sage, Kara D.; Baldwin, Dare

2015-01-01

Past research has established that children typically learn better from live demonstrations than from two-dimensional (2D) media. In the present set of experiments, we investigated the efficacy of a new 2D learning medium-the self-paced slideshow. A primary goal was to determine whether the "video deficit effect" extended to self-paced…

Isoflurane Damages the Developing Brain of Mice and Induces Subsequent Learning and Memory Deficits through FASL-FAS Signaling

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Xiuwen Yi

2015-01-01

Full Text Available Background. Isoflurane disrupts brain development of neonatal mice, but its mechanism is unclear. We explored whether isoflurane damaged developing hippocampi through FASL-FAS signaling pathway, which is a well-known pathway of apoptosis. Method. Wild type and FAS- or FASL-gene-knockout mice aged 7 days were exposed to either isoflurane or pure oxygen. We used western blotting to study expressions of caspase-3, FAS (CD95, and FAS ligand (FASL or CD95L proteins, TUNEL staining to count apoptotic cells in hippocampus, and Morris water maze (MWM to evaluate learning and memory. Result. Isoflurane increased expression of FAS and FASL proteins in wild type mice. Compared to isoflurane-treated FAS- and FASL-knockout mice, isoflurane-treated wild type mice had higher expression of caspase-3 and more TUNEL-positive hippocampal cells. Expression of caspase-3 in wild isoflurane group, wild control group, FAS/FASL-gene-knockout control group, and FAS/FASL-gene-knockout isoflurane group showed FAS or FASL gene knockout might attenuate increase of caspase-3 caused by isoflurane. MWM showed isoflurane treatment of wild type mice significantly prolonged escape latency and reduced platform crossing times compared with gene-knockout isoflurane-treated groups. Conclusion. Isoflurane induces apoptosis in developing hippocampi of wild type mice but not in FAS- and FASL-knockout mice and damages brain development through FASL-FAS signaling.

Memory deficits in abstinent MDMA (ecstasy) users: neuropsychological evidence of frontal dysfunction.

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Quednow, Boris B; Jessen, Frank; Kuhn, Kai-Uwe; Maier, Wolfgang; Daum, Irene; Wagner, Michael

2006-05-01

Chronic administration of the common club drug 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is associated with long-term depletion of serotonin (5-HT) and loss of 5-HT axons in the brains of rodents and non-human primates, and evidence suggests that recreational MDMA consumption may also affect the human serotonergic system. Moreover, it was consistently shown that abstinent MDMA users have memory deficits. Recently, it was supposed that these deficits are an expression of a temporal or rather hippocampal dysfunction caused by the serotonergic neurotoxicity of MDMA. The aim of this study is to examine the memory deficits of MDMA users neuropsychologically in order to evaluate the role of different brain regions. Nineteen male abstinent MDMA users, 19 male abstinent cannabis users and 19 male drug-naive control subjects were examined with a German version of the Rey Auditory Verbal Learning Test (RAVLT). MDMA users showed widespread and marked verbal memory deficits, compared to drug-naive controls as well as compared to cannabis users, whereas cannabis users did not differ from control subjects in their memory performance. MDMA users revealed impairments in learning, consolidation, recall and recognition. In addition, they also showed a worse recall consistency and strong retroactive interference whereby both measures were previously associated with frontal lobe function. There was a significant correlation between memory performance and the amount of MDMA taken. These results suggest that the memory deficits of MDMA users are not only the result of a temporal or hippocampal dysfunction, but also of a dysfunction of regions within the frontal cortex.

Dissociation between sensitization and learning-related neuromodulation in an aplysiid species.

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Erixon, N J; Demartini, L J; Wright, W G

1999-06-14

Previous phylogenetic analyses of learning and memory in an opisthobranch lineage uncovered a correlation between two learning-related neuromodulatory traits and their associated behavioral phenotypes. In particular, serotonin-induced increases in sensory neuron spike duration and excitability, which are thought to underlie several facilitatory forms of learning in Aplysia, appear to have been lost over the course of evolution in a distantly related aplysiid, Dolabrifera dolabrifera. This deficit is paralleled by a behavioral deficit: individuals of Dolabrifera do not express generalized sensitization (reflex enhancement of an unhabituated response after a noxious stimulus is applied outside of the reflex receptive field) or dishabituation (reflex enhancement of a habituated reflex). The goal of the present study was to confirm and extend this correlation by testing for the neuromodulatory traits and generalized sensitization in an additional species, Phyllaplysia taylori, which is closely related to Dolabrifera. Instead, our results indicated a lack of correlation between the neuromodulatory and behavioral phenotypes. In particular, sensory neuron homologues in Phyllaplysia showed the ancestral neuromodulatory phenotype typified by Aplysia. Bath-applied 10 microM serotonin significantly increased homologue spike duration and excitability. However, when trained with the identical apparatus and protocols that produced generalized sensitization in Aplysia, individuals of Phyllaplysia showed no evidence of sensitization. Thus, this species expresses the neuromodulatory phenotype of its ancestors while appearing to express the behavioral phenotype of its near relative. These results suggests that generalized sensitization can be lost during the course of evolution in the absence of a deficit in these two neuromodulatory traits, and raises the possibility that the two traits may support some other form of behavioral plasticity in Phyllaplysia. The results also raise the

Chemogenetic activation of the lateral hypothalamus reverses early life stress-induced deficits in motivational drive.

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Campbell, Erin J; Mitchell, Caitlin S; Adams, Cameron D; Yeoh, Jiann Wei; Hodgson, Deborah M; Graham, Brett A; Dayas, Christopher V

2017-10-01

Altered motivated behaviour is a cardinal feature of several neuropsychiatric conditions including mood disorders. One well-characterized antecedent to the development of mood disorders is exposure to early life stress (ELS). A key brain substrate controlling motivated behaviour is the lateral hypothalamus (LH). Here, we examined the effect of ELS on LH activation and the motivation to self-administer sucrose. We tested whether chemogenetic activation of LH circuits could modify sucrose responding in ELS rats and examined the impact on LH cell populations. Male rat pups were maternally separated for 0 or 3 h on postnatal days 2-14. During adolescence, rats received bilateral injections of hM3D(Gq), the excitatory designer receptor exclusively activated by designer drugs, into LH. In adulthood, rats were trained to self-administer sucrose and tested under a progressive ratio schedule to determine their motivation for reward following injection with either vehicle or 5 mg/kg clozapine-N-oxide. Brains were processed for Fos-protein immunohistochemistry. ELS significantly suppressed lever responding for sucrose, indicating a long-lasting impact of ELS on motivation circuits. hM3D(Gq) activation of LH increased responding, normalizing deficits in ELS rats, and increased Fos-positive orexin and MCH cell numbers within LH. Our findings indicate that despite being susceptible to environmental stressors, LH circuits retain the capacity to overcome ELS-induced deficits in motivated behaviour. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Moderate injury in motor-sensory cortex causes behavioral deficits accompanied by electrophysiological changes in mice adulthood.

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Wei Ouyang

Full Text Available Moderate traumatic brain injury (TBI in children often happen when there's a sudden blow to the frontal bone, end with long unconscious which can last for hours and progressive cognitive deficits. However, with regard to the influences of moderate TBI during children adulthood, injury-induced alterations of locomotive ability, long-term memory performance, and hippocampal electrophysiological firing changes have not yet been fully identified. In this study, lateral fluid percussion (LFP method was used to fabricate moderate TBI in motor and somatosensory cortex of the 6-weeks-old mice. The motor function, learning and memory function, extracellular CA1 neural spikes were assessed during acute and subacute phase. Moreover, histopathology was performed on day post injury (DPI 16 to evaluate the effect of TBI on tissue and cell morphological changes in cortical and hippocampal CA1 subregions. After moderate LFP injury, the 6-weeks-old mice showed severe motor deficits at the early stage in acute phase but gradually recovered later during adulthood. At the time points in acute and subacute phase after TBI, novel object recognition (NOR ability and spatial memory functions were consistently impaired in TBI mice; hippocampal firing frequency and burst probability were hampered. Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop. These electrophysiological impacts were associated with substantially lowered NOR preference as compared to the sham group during adulthood. These results suggest that moderate TBI introduced at motorsenory cortex in 6-weeks-old mice causes obvious motor and cognitive deficits during their adulthood. While the locomotive ability progressively recovers, the cognitive deficits persisted while the mice mature as adult mice. The cognitive deficits may be attributed to the general suppressing of whole neural network, which could be labeled by marked reduction of excitability in hippocampal CA1

Moderate injury in motor-sensory cortex causes behavioral deficits accompanied by electrophysiological changes in mice adulthood.

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Ouyang, Wei; Yan, Qichao; Zhang, Yu; Fan, Zhiheng

2017-01-01

Moderate traumatic brain injury (TBI) in children often happen when there's a sudden blow to the frontal bone, end with long unconscious which can last for hours and progressive cognitive deficits. However, with regard to the influences of moderate TBI during children adulthood, injury-induced alterations of locomotive ability, long-term memory performance, and hippocampal electrophysiological firing changes have not yet been fully identified. In this study, lateral fluid percussion (LFP) method was used to fabricate moderate TBI in motor and somatosensory cortex of the 6-weeks-old mice. The motor function, learning and memory function, extracellular CA1 neural spikes were assessed during acute and subacute phase. Moreover, histopathology was performed on day post injury (DPI) 16 to evaluate the effect of TBI on tissue and cell morphological changes in cortical and hippocampal CA1 subregions. After moderate LFP injury, the 6-weeks-old mice showed severe motor deficits at the early stage in acute phase but gradually recovered later during adulthood. At the time points in acute and subacute phase after TBI, novel object recognition (NOR) ability and spatial memory functions were consistently impaired in TBI mice; hippocampal firing frequency and burst probability were hampered. Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop. These electrophysiological impacts were associated with substantially lowered NOR preference as compared to the sham group during adulthood. These results suggest that moderate TBI introduced at motorsenory cortex in 6-weeks-old mice causes obvious motor and cognitive deficits during their adulthood. While the locomotive ability progressively recovers, the cognitive deficits persisted while the mice mature as adult mice. The cognitive deficits may be attributed to the general suppressing of whole neural network, which could be labeled by marked reduction of excitability in hippocampal CA1 subregion.

The selective positive allosteric M1 muscarinic receptor modulator PQCA attenuates learning and memory deficits in the Tg2576 Alzheimer's disease mouse model.

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Puri, Vanita; Wang, Xiaohai; Vardigan, Joshua D; Kuduk, Scott D; Uslaner, Jason M

2015-01-01

We have recently shown that the M1 muscarinic receptor positive allosteric modulator, PQCA, improves cognitive performance in rodents and non-human primates administered the muscarinic receptor antagonist scopolamine. The purpose of the present experiments was to characterize the effects of PQCA in a model more relevant to the disease pathology of Alzheimer's disease. Tg2576 transgenic mice that have elevated Aβ were tested in the novel object recognition task to characterize recognition memory as a function of age and treatment with the PQCA. The effects of PQCA were compared to the acetylcholinesterase inhibitor donepezil, the standard of care for Alzheimer's disease. In addition, the effect of co-administering PQCA and donepezil was evaluated. Aged Tg2576 mice demonstrated a deficit in recognition memory that was significantly attenuated by PQCA. The positive control donepezil also reversed the deficit. Furthermore, doses of PQCA and donepezil that were inactive on their own were found to improve recognition memory when given together. These studies suggest that M1 muscarinic receptor positive allosteric modulation can ameliorate memory deficits in disease relevant models of Alzheimer's disease. These data, combined with our previous findings demonstrating PQCA improves scopolamine-induced cognitive deficits in both rodents and non-human primates, suggest that M1 positive allosteric modulators have therapeutic potential for the treatment of Alzheimer's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Celecoxib Alleviates Memory Deficits by Downregulation of COX-2 Expression and Upregulation of the BDNF-TrkB Signaling Pathway in a Diabetic Rat Model.

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Yang, Ying; Gao, Ling

2017-06-01

Previous studies conveyed that diabetes causes learning and memory deficits. Data also suggest that celecoxib exerts an anti-hyperalgesic, anti-allodynic, and a plethora of other beneficial effects in diabetic rats. However, whether celecoxib could alleviate memory deficit in diabetic rat is unknown. In the present study, we aimed to examine the potential of celecoxib to counter memory deficits in diabetes. Experimental diabetes was induced by streptozotocin (STZ, 60 mg/kg) in male SD rats. Rats were divided into three groups (n = 16/group): normal control group injected with normal saline, diabetes group injected with STZ, and diabetes + celecoxib group in which diabetic rats were administered with celecoxib by gavage in drinking water (10 mg/kg) for 10 days in terms of which memory performance in animals was measured, hippocampal tissue harvested, and long-term potentiation assessed. Western blotting and immunohistochemical staining were performed to determine cyclooxygenase 2 (COX-2) expression in hippocampus. The results showed that a rat model of STZ-induced diabetes was successfully established and that celecoxib treatment significantly improved the associated nephropathy and inflammation. Moreover, spatial memory and hippocampal long-term potentiation (LTP) were impaired in diabetic model (P memory deficit and hippocampal LTP in the diabetic rats. To understand the underlying mechanisms, the expression of some important pathways involved in memory impairment was determined. We found that brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin-related kinase (p-TrkB) were decreased in diabetic rats but were effectively reversed by celecoxib treatment. As evidenced by western blotting and immunohistochemical staining, the expression of COX-2 in hippocampus was significantly upregulated in diabetic rat (P memory deficits via probable downregulation of hippocampal COX-2 expression and upregulation of the BDNF-TrkB signaling pathway in a

Written Composition Performance of Students with Attention-Deficit/Hyperactivity Disorder

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Casas, Ana Miranda; Ferrer, Manuel Soriano; Fortea, Inmaculada Baixauli

2013-01-01

Attention-deficit/hyperactivity disorder (ADHD) is frequently associated with learning disabilities. The present study examined the written composition of children with ADHD, which depends to a large degree on continuous self-regulation and attentional control skills for organizing information and maintaining the level of effort. Fifty children…

[Adaptive behaviour and learning in children with neurodevelopmental disorders (autism spectrum disorders and attention deficit hyperactivity disorder). Effects of executive functioning].

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Rosello-Miranda, B; Berenguer-Forner, C; Miranda-Casas, A

2018-03-01

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) present difficulties in adaptive functioning and learning, possibly associated with failures in executive functioning characteristic of both disorders. To analyze the impact of executive functioning in the adaptive behaviors of socialization and daily life and in learning behaviors in children with ASD and children with ADHD. The participants were 124 children matched in age and intellectual quotient: 37 children with typical development, 52 children with ASD and 35 children with ADHD. Parents reported on their children's adaptive behaviors, while teachers provided information on learning behaviors and executive functioning in daily life. There are significant differences between the groups with ASD and ADHD with the typical development group in all domains evaluated. In addition, the group with ASD had worse socialization skills while persistence in learning was more affected in children with ADHD. Finally, the metacognitive index of executive functioning predicted the socialization and persistence of children with ASD. On the other hand, the index of behavioral regulation and the educational level of the parents predicted the socialization skills in children with ADHD. The results highlight the need to include differentiated executive strategies in the intervention of children with ASD and children with ADHD.

Fronto-striatal grey matter contributions to discrimination learning in Parkinson's disease

NARCIS (Netherlands)

O'Callaghan, C.; Moustafa, A.A.; de Wit, S.; Shine, J.M.; Robbins, T.W.; Lewis, S.J.G.; Hornberger, M.

2013-01-01

Discrimination learning deficits in Parkinson's disease (PD) have been well-established. Using both behavioral patient studies and computational approaches, these deficits have typically been attributed to dopamine imbalance across the basal ganglia. However, this explanation of impaired learning in

Endothelial ErbB4 deficit induces alterations in exploratory behavior and brain energy metabolism in mice.

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Wu, Gang; Liu, Xiu-Xiu; Lu, Nan-Nan; Liu, Qi-Bing; Tian, Yun; Ye, Wei-Feng; Jiang, Guo-Jun; Tao, Rong-Rong; Han, Feng; Lu, Ying-Mei

2017-06-01

The receptor tyrosine kinase ErbB4 is present throughout the primate brain and has a distinct functional profile. In this study, we investigate the potential role of endothelial ErbB4 receptor signaling in the brain. Here, we show that the endothelial cell-specific deletion of ErbB4 induces decreased exploratory behavior in adult mice. However, the water maze task for spatial memory and the memory reconsolidation test reveal no changes; additionally, we observe no impairment in CaMKII phosphorylation in Cdh5Cre;ErbB4 f/f mice, which indicates that the endothelial ErbB4 deficit leads to decreased exploratory activity rather than direct memory deficits. Furthermore, decreased brain metabolism, which was measured using micro-positron emission tomography, is observed in the Cdh5Cre;ErbB4 f/f mice. Consistently, the immunoblot data demonstrate the downregulation of brain Glut1, phospho-ULK1 (Ser555), and TIGAR in the endothelial ErbB4 conditional knockout mice. Collectively, our findings suggest that endothelial ErbB4 plays a critical role in regulating brain function, at least in part, through maintaining normal brain energy homeostasis. Targeting ErbB4 or the modulation of endothelial ErbB4 signaling may represent a rational pharmacological approach to treat neurological disorders. © 2017 John Wiley & Sons Ltd.

Neural oscillatory deficits in schizophrenia predict behavioral and neurocognitive impairments

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Antigona eMartinez

2015-07-01

Full Text Available Paying attention to visual stimuli is typically accompanied by event-related desynchronizations (ERD of ongoing alpha (7-14 Hz activity in visual cortex. The present study used time-frequency based analyses to investigate the role of impaired alpha ERD in visual processing deficits in schizophrenia (Sz. Subjects viewed sinusoidal gratings of high (HSF and low (LSF spatial frequency designed to test functioning of the parvo- versus magnocellular pathways, respectively. Patients with Sz and healthy controls paid attention selectively to either the LSF or HSF gratings which were presented in random order. Event-related brain potentials (ERPs were recorded to all stimuli. As in our previous study, it was found that Sz patients were selectively impaired at detecting LSF target stimuli and that ERP amplitudes to LSF stimuli were diminished, both for the early sensory-evoked components and for the attend minus unattend difference component (the Selection Negativity, which is generally regarded as a specific index of feature-selective attention. In the time-frequency domain, the differential ERP deficits to LSF stimuli were echoed in a virtually absent theta-band phase locked response to both unattended and attended LSF stimuli (along with relatively intact theta-band activity for HSF stimuli. In contrast to the theta-band evoked responses which were tightly stimulus locked, stimulus-induced desynchronizations of ongoing alpha activity were not tightly stimulus locked and were apparent only in induced power analyses. Sz patients were significantly impaired in the attention-related modulation of ongoing alpha activity for both HSF and LSF stimuli. These deficits correlated with patients’ behavioral deficits in visual information processing as well as with visually based neurocognitive deficits. These findings suggest an additional, pathway-independent, mechanism by which deficits in early visual processing contribute to overall cognitive impairment in

Establishing a pharmacotherapy induced ototoxicity programme within a service-learning approach

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Natalie Schellack

2015-06-01

Full Text Available Pharmacotherapy-induced ototoxicity is growing, especially in developing countries such as South Africa. This highlights the importance of ototoxicity monitoring and management of hearing loss. This article focuses on the establishment of an ototoxicity clinic as a site for the implementation of a service-learning module in the Audiology programme. The clinic offers a unique opportunity of collaboration between pharmacists and an audiologist where pharmacotherapy-induced ototoxicity is uniquely monitored. The Sefako Makgatho Health Sciences University (SMU provides training to both the disciplines audiology and pharmacy. The main aim of this article is to describe how ototoxicity monitoring is implemented in the curriculum within such an academic service-learning approach. Through service learning students develop a deeper understanding of course content, acquire new knowledge and engage in civic activity. It simultaneously provides a unique opportunity for interdisciplinary collaboration between the disciplines of audiology and pharmacy. The objectives for this programme are therefore to facilitate learning and to provide a service to the local community by identifying, preventing and monitoring medicine-induced hearing loss in in-hospital and out-patients; as well as to establish inter-disciplinary collaboration between the disciplines and stakeholders for more effective service delivery. The constant interdisciplinary teamwork between the audiologist, pharmacist, physician and nursing staff in the wards results in best practice and management of patients with ototoxic damage.

Early life stress induces attention-deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model.

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Bock, J; Breuer, S; Poeggel, G; Braun, K

2017-03-01

In a novel animal model Octodon degus we tested the hypothesis that, in addition to genetic predisposition, early life stress (ELS) contributes to the etiology of attention-deficit hyperactivity disorder-like behavioral symptoms and the associated brain functional deficits. Since previous neurochemical observations revealed that early life stress impairs dopaminergic functions, we predicted that these symptoms can be normalized by treatment with methylphenidate. In line with our hypothesis, the behavioral analysis revealed that repeated ELS induced locomotor hyperactivity and reduced attention towards an emotionally relevant acoustic stimulus. Functional imaging using ( 14 C)-2-fluoro-deoxyglucose-autoradiography revealed that the behavioral symptoms are paralleled by metabolic hypoactivity of prefrontal, mesolimbic and subcortical brain areas. Finally, the pharmacological intervention provided further evidence that the behavioral and metabolic dysfunctions are due to impaired dopaminergic neurotransmission. Elevating dopamine in ELS animals by methylphenidate normalized locomotor hyperactivity and attention-deficit and ameliorated brain metabolic hypoactivity in a dose-dependent manner.

Experimentally Induced Learned Helplessness: How Far Does it Generalize?

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Tuffin, Keith; And Others

1985-01-01

Assessed whether experimentally induced learned helplessness on a cognitive training task generalized to a situationally dissimilar social interaction test task. No significant differences were observed between groups on the subsequent test task, showing that helplessness failed to generalize. (Author/ABB)

Remodeling of hippocampal spine synapses in the rat learned helplessness model of depression.

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Hajszan, Tibor; Dow, Antonia; Warner-Schmidt, Jennifer L; Szigeti-Buck, Klara; Sallam, Nermin L; Parducz, Arpad; Leranth, Csaba; Duman, Ronald S

2009-03-01

Although it has been postulated for many years that depression is associated with loss of synapses, primarily in the hippocampus, and that antidepressants facilitate synapse growth, we still lack ultrastructural evidence that changes in depressive behavior are indeed correlated with structural synaptic modifications. We analyzed hippocampal spine synapses of male rats (n=127) with electron microscopic stereology in association with performance in the learned helplessness paradigm. Inescapable footshock (IES) caused an acute and persistent loss of spine synapses in each of CA1, CA3, and dentate gyrus, which was associated with a severe escape deficit in learned helplessness. On the other hand, IES elicited no significant synaptic alterations in motor cortex. A single injection of corticosterone reproduced both the hippocampal synaptic changes and the behavioral responses induced by IES. Treatment of IES-exposed animals for 6 days with desipramine reversed both the hippocampal spine synapse loss and the escape deficit in learned helplessness. We noted, however, that desipramine failed to restore the number of CA1 spine synapses to nonstressed levels, which was associated with a minor escape deficit compared with nonstressed control rats. Shorter, 1-day or 3-day desipramine treatments, however, had neither synaptic nor behavioral effects. These results indicate that changes in depressive behavior are associated with remarkable remodeling of hippocampal spine synapses at the ultrastructural level. Because spine synapse loss contributes to hippocampal dysfunction, this cellular mechanism may be an important component in the neurobiology of stress-related disorders such as depression.

Isoflurane Exposure Rescues Short-term Learning and Memory in Sleep-Disturbed Drosophila melanogaster.

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Zena Chatila

2017-10-01

Full Text Available Sleep is known to play an important role in cognition, learning and memory. As Drosophila melanogaster have stable circadian rhythms and behavioral states similar to those of human sleep, they have been a useful model to investigate the effects of sleep on learning and memory. General anesthesia has been shown to cause cognitive impairments in humans. However, anesthesia also induces a behavioral state similar to sleep and may activate sleep pathways. This study examined learning and memory after an acute exposure of isoflurane in a Drosophila mutant model of restless leg syndrome. There were two possible outcomes: isoflurane (an anesthetic could have impaired cognitive functioning or enhanced learning and memory by activating sleep pathways. Given the acute cognitive impairments often observed postoperatively, we believed the former outcome to be the most likely. Flies with fragmented sleep had impaired performance on an aversive phototaxic suppression learning and memory task compared to wildtype flies. This deficit was rescued with isoflurane exposure, as no differences in learning were observed between mutant and wildtype flies treated with anesthesia. This result suggests that anesthesia exposure can ameliorate impaired learning and memory due to sleep fragmentation. Further investigations are required to determine the type of memory impacted by anesthesia and the mechanisms by which anesthesia induces this effect.

Brain and behavioural correlates of action semantic deficits in autism.

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Rachel Louise Moseley

2013-11-01

Full Text Available Action-perception circuits comprising neurons in the motor system have been proposed as main building blocks of higher cognition; accordingly, motor dysfunction should entail cognitive deficits. Autism spectrum conditions (ASC are marked by motor impairments but the implications of such motor dysfunction for higher cognition remain unclear. We here used word reading and semantic judgement tasks to interrogate action-related motor cognition and its corresponding fMRI brain activation in high-functioning adults with ASC. These participants exhibited hypoactivity of motor cortex in language processing relative to typically developing (TD controls. Crucially, we also found a deficit in semantic processing of action-related words, which, intriguingly, significantly correlated with their underactivation of motor cortex to these items. Furthermore, the word-induced hypoactivity in the motor system also predicted the severity of ASC as expressed by the number of autistic symptoms measured by the Autism-Spectrum Quotient (Baron-Cohen et al, 2001. These significant correlations between word-induced activation of the motor system and a newly discovered semantic deficit in a condition known to be characterised by motor impairments, along with the correlation of such activation with general autistic traits confirm critical predictions of causal theories explaining cognitive and semantic deficits in ASC, in part, to dysfunctional action-perception circuits and resultant reduction of motor system activation.

Long-term cognitive deficits accompanied by reduced neurogenesis after soman poisoning

NARCIS (Netherlands)

Joosen, M.J.A.; Jousma, E.; van den Boom, T.M.; Kuijpers, W.C.; Smit, A.B.; Lucassen, P.J.; van Helden, H.P.M.

2009-01-01

To date, treatment of organophosphate (OP) poisoning shows several shortcomings, and OP-victims might suffer from lasting cognitive deficits and sleep-wake disturbances. In the present study, long-term effects of soman poisoning on learning ability, memory and neurogenesis were investigated in rats,

HIV-infected persons with bipolar disorder are less aware of memory deficits as compared to HIV-infected persons without bipolar disorder

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Blackstone, Kaitlin; Tobin, Alexis; Posada, Carolina; Gouaux, Ben; Grant, Igor; Moore, David J.

2012-01-01

Episodic memory deficits are common in HIV infection and bipolar disorder, but patient insight into such deficits remains unclear. Thirty-four HIV-infected individuals without bipolar disorder l(HIV+/BD−) and 47 HIV+ individuals with comorbid bipolar disorder (HIV+/BD+) were administered the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised to examine objective learning/memory functioning. Subjective memory complaints were assessed via the memory subscale of ...

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

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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.

Learning of grammar-like visual sequences by adults with and without language-learning disabilities.

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Aguilar, Jessica M; Plante, Elena

2014-08-01

Two studies examined learning of grammar-like visual sequences to determine whether a general deficit in statistical learning characterizes this population. Furthermore, we tested the hypothesis that difficulty in sustaining attention during the learning task might account for differences in statistical learning. In Study 1, adults with normal language (NL) or language-learning disability (LLD) were familiarized with the visual artificial grammar and then tested using items that conformed or deviated from the grammar. In Study 2, a 2nd sample of adults with NL and LLD were presented auditory word pairs with weak semantic associations (e.g., groom + clean) along with the visual learning task. Participants were instructed to attend to visual sequences and to ignore the auditory stimuli. Incidental encoding of these words would indicate reduced attention to the primary task. In Studies 1 and 2, both groups demonstrated learning and generalization of the artificial grammar. In Study 2, neither the NL nor the LLD group appeared to encode the words presented during the learning phase. The results argue against a general deficit in statistical learning for individuals with LLD and demonstrate that both NL and LLD learners can ignore extraneous auditory stimuli during visual learning.

The procedural learning deficit hypothesis of language learning disorders: we see some problems.

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West, Gillian; Vadillo, Miguel A; Shanks, David R; Hulme, Charles

2018-03-01

Impaired procedural learning has been suggested as a possible cause of developmental dyslexia (DD) and specific language impairment (SLI). This study examined the relationship between measures of verbal and non-verbal implicit and explicit learning and measures of language, literacy and arithmetic attainment in a large sample of 7 to 8-year-old children. Measures of verbal explicit learning were correlated with measures of attainment. In contrast, no relationships between measures of implicit learning and attainment were found. Critically, the reliability of the implicit learning tasks was poor. Our results show that measures of procedural learning, as currently used, are typically unreliable and insensitive to individual differences. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=YnvV-BvNWSo. 2017 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

Blue-yellow colour vision impairment and cognitive deficits in occasional and dependent stimulant users.

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Hulka, Lea M; Wagner, Michael; Preller, Katrin H; Jenni, Daniela; Quednow, Boris B

2013-04-01

Specific blue-yellow colour vision impairment has been reported in dependent cocaine users and it was postulated that drug-induced changes in retinal dopamine neurotransmission are responsible. However, it is unclear whether these changes are confined to chronic cocaine users, whether they are specific for dopaminergic stimulants such as cocaine and amphetamine and whether they are related to cognitive functions such as working memory, encoding and consolidation. In 47 occasional and 29 dependent cocaine users, 23 MDMA (commonly known as 'ecstasy') users and 47 stimulant-naive controls, colour vision discrimination was measured with the Lanthony Desaturated Panel D-15 Test and memory performance with the Auditory Verbal Learning Test. Both occasional and dependent cocaine users showed higher colour confusion indices than controls. Users of the serotonergic stimulant MDMA (26%), occasional (30%) and dependent cocaine users (34%) exhibited more frequent blue-yellow colour vision disorders compared to controls (9%). Inferior performance of MDMA users was caused by a subgroup with high amphetamine co-use (55%), while MDMA use alone was not associated with decreased blue-yellow discrimination (0%). Cognitive performance was worse in cocaine users with colour vision disorder compared to users and controls with intact colour vision and both colour vision impairment and cognitive deficits were related to cocaine use. Occasional cocaine and amphetamine use might induce blue-yellow colour vision impairment, whereas the serotonergic stimulant MDMA does not impair colour vision. The association between colour vision impairment and cognitive deficits in cocaine users may reflect that retinal and cerebral dopamine alterations are linked to a certain degree.

Rescue of Learning and Memory Deficits in the Human Nonsyndromic Intellectual Disability Cereblon Knock-Out Mouse Model by Targeting the AMP-Activated Protein Kinase-mTORC1 Translational Pathway.

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Bavley, Charlotte C; Rice, Richard C; Fischer, Delaney K; Fakira, Amanda K; Byrne, Maureen; Kosovsky, Maria; Rizzo, Bryant K; Del Prete, Dolores; Alaedini, Armin; Morón, Jose A; Higgins, Joseph J; D'Adamio, Luciano; Rajadhyaksha, Anjali M

2018-03-14

A homozygous nonsense mutation in the cereblon ( CRBN ) gene results in autosomal recessive, nonsyndromic intellectual disability that is devoid of other phenotypic features, suggesting a critical role of CRBN in mediating learning and memory. In this study, we demonstrate that adult male Crbn knock-out ( Crbn KO ) mice exhibit deficits in hippocampal-dependent learning and memory tasks that are recapitulated by focal knock-out of Crbn in the adult dorsal hippocampus, with no changes in social or repetitive behavior. Cellular studies identify deficits in long-term potentiation at Schaffer collateral CA1 synapses. We further show that Crbn is robustly expressed in the mouse hippocampus and Crbn KO mice exhibit hyperphosphorylated levels of AMPKα (Thr172). Examination of processes downstream of AMP-activated protein kinase (AMPK) finds that Crbn KO mice have a selective impairment in mediators of the mTORC1 translation initiation pathway in parallel with lower protein levels of postsynaptic density glutamatergic proteins and higher levels of excitatory presynaptic markers in the hippocampus with no change in markers of the unfolded protein response or autophagy pathways. Acute pharmacological inhibition of AMPK activity in adult Crbn KO mice rescues learning and memory deficits and normalizes hippocampal mTORC1 activity and postsynaptic glutamatergic proteins without altering excitatory presynaptic markers. Thus, this study identifies that loss of Crbn results in learning, memory, and synaptic defects as a consequence of exaggerated AMPK activity, inhibition of mTORC1 signaling, and decreased glutamatergic synaptic proteins. Thus, Crbn KO mice serve as an ideal model of intellectual disability to further explore molecular mechanisms of learning and memory. SIGNIFICANCE STATEMENT Intellectual disability (ID) is one of the most common neurodevelopmental disorders. The cereblon ( CRBN ) gene has been linked to autosomal recessive, nonsyndromic ID, characterized by an

MRI Anatomical Correlates of Reading and Language Deficits

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J Gordon Millichap

2006-12-01

Full Text Available Neuroanatomical correlates of developmental dyslexia (DD, defined by isolated reading deficits, and specific language impairment (SLI, defined by poor receptive and expressive language skills, were examined using MR imaging in a heterogeneous sample of 14 boys and 8 girls (11-16 yers of age with learning disabilities, in a study at University of Florida; Georgetown University, Washington, DC; and other centers.

Minocycline attenuates cognitive impairment induced by isoflurane anesthesia in aged rats.

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Feijuan Kong

Full Text Available Postoperative cognitive dysfunction (POCD is a clinical phenomenon characterized by cognitive deficits in patients after anesthesia and surgery, especially in geriatric surgical patients. Although it has been documented that isoflurane exposure impaired cognitive function in several aged animal models, there are few clinical interventions and treatments available to prevent this disorder. Minocycline has been well established to exert neuroprotective effects in various experimental animal models and neurodegenerative diseases. Therefore, we hypothesized that pretreatment with minocycline attenuates isoflurane-induced cognitive decline in aged rats. In the present study, twenty-month-old rats were administered minocycline or an equal volume of saline by intraperitoneal injection 12 h before exposure to isoflurane. Then the rats were exposed to 1.3% isoflurane for 4 h. Two weeks later, spatial learning and memory of the rats were examined using the Morris Water Maze. We found that pretreatment with minocycline mitigated isoflurane-induced cognitive deficits and suppressed the isoflurane-induced excessive release of IL-1β and caspase-3 in the hippocampal CA1 region at 4 h after isoflurane exposure, as well as the number of TUNEL-positive nuclei. In addition, minocycline treatment also prevented the changes of synaptic ultrastructure in the hippocampal CA1 region induced by isoflurane. In conclusion, pretreatment with minocycline attenuated isoflurane-induced cognitive impairment in aged rats.

Neurocognitive pattern analysis reveals classificatory hierarchy of attention deficits in schizophrenia.

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Shen, Christina; Popescu, Florin C; Hahn, Eric; Ta, Tam T M; Dettling, Michael; Neuhaus, Andres H

2014-07-01

Attention deficits, among other cognitive deficits, are frequently observed in schizophrenia. Although valid and reliable neurocognitive tasks have been established to assess attention deficits in schizophrenia, the hierarchical value of those tests as diagnostic discriminants on a single-subject level remains unclear. Thus, much research is devoted to attention deficits that are unlikely to be translated into clinical practice. On the other hand, a clear hierarchy of attention deficits in schizophrenia could considerably aid diagnostic decisions and may prove beneficial for longitudinal monitoring of therapeutic advances. To propose a diagnostic hierarchy of attention deficits in schizophrenia, we investigated several facets of attention in 86 schizophrenia patients and 86 healthy controls using a set of established attention tests. We applied state-of-the-art machine learning algorithms to determine attentive test variables that enable an automated differentiation between schizophrenia patients and healthy controls. After feature preranking, hypothesis building, and hypothesis validation, the polynomial support vector machine classifier achieved a classification accuracy of 90.70% ± 2.9% using psychomotor speed and 3 different attention parameters derived from sustained and divided attention tasks. Our study proposes, to the best of our knowledge, the first hierarchy of attention deficits in schizophrenia by identifying the most discriminative attention parameters among a variety of attention deficits found in schizophrenia patients. Our results offer a starting point for hierarchy building of schizophrenia-associated attention deficits and contribute to translating these concepts into diagnostic and therapeutic practice on a single-subject level. © The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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

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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…

ACTH Prevents Deficits in Fear Extinction Associated with Early Life Seizures

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Andrew T Massey

2016-05-01

Full Text Available Early life seizures are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of early life seizures (ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action. We found that while rats with a history of ELS were able to acquire a conditioned fear learning paradigm as well as controls, these rats had significant deficits in their ability to extinguish fearful memories. ACTH treatment did not alter any seizure parameters but nevertheless was able to significantly improve this fear extinction, while dexamethasone treatment during the same period did not. This ACTH effect was specific for fear extinction deficits and not for spatial learning deficits in a water maze. Additionally, ACTH did not alter seizure latency or duration suggesting that cognitive and seizure outcomes may be dissociable. Expression levels of melanocortin receptors, which bind ACTH, were found to be significantly lower in animals that had experienced ELS than in control animals, potentially implicating central melanocortin receptor dysregulation in the effects of ELS and suggesting a mechanism of action for ACTH. Taken together, these data suggest that early treatment with ACTH can have significant long-term consequences for cognition in animals with a history of ELS independently of seizure cessation, and may act in part through a CNS melanocortin receptor pathway.

Artificial Grammar Learning in Dyslexic and Nondyslexic Adults: Implications for Orthographic Learning

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Samara, Anna; Caravolas, Markéta

2017-01-01

Potential implicit orthographic learning deficits were investigated in adults with dyslexia. An artificial grammar learning paradigm served to assess dyslexic and typical readers' ability to exploit information about chunk frequency, letter-position patterns, and specific string similarity, all of which have analogous constructs in real…

Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits.

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Orchard, Tonya S; Gaudier-Diaz, Monica M; Weinhold, Kellie R; Courtney DeVries, A

2017-02-01

Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis. Dietary approaches that modify inflammation and neurogenesis are promising strategies for reducing chemotherapy-induced cognitive deficits in breast cancer survivors. In this review, we describe the cognitive and neuronal side effects associated with commonly used chemotherapy treatments for breast cancer, and we focus on the often opposing actions of omega-3 fatty acids and added sugars on cognitive function, neuroinflammation, and adult hippocampal neurogenesis. Omega-3 fatty acids administered concurrently with doxorubicin chemotherapy have been shown to prevent depressive-like behaviors and reduce neuroinflammation, oxidative stress, and neural apoptosis in rodent models. In contrast, diets high in added sugars may interact with n-3 FAs to diminish their anti-inflammatory activity or act independently to increase neuroinflammation, reduce adult hippocampal neurogenesis, and promote cognitive deficits. We propose that a diet rich in long-chain, marine-derived omega-3 fatty acids and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress, thereby protecting neurons from the toxic effects of chemotherapy. Research testing this hypothesis could lead to the identification of modifiable dietary choices to reduce the long-term impact of chemotherapy on the

Caffeine improves attention deficit in neonatal 6-OHDA lesioned rats, an animal model of attention deficit hyperactivity disorder (ADHD).

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Caballero, Miguel; Núñez, Fabiana; Ahern, Siobhán; Cuffí, Maria L; Carbonell, Lourdes; Sánchez, Silvia; Fernández-Dueñas, Víctor; Ciruela, Francisco

2011-04-20

Nowadays the pharmacological treatment of the attention deficit hyperactivity disorder (ADHD) is based on amphetamine derivatives (i.e. methylphenidate). However, these drugs induce a large array of adverse side effects, thus less aggressive psychostimulant drugs (i.e. caffeine) are being proposed in the management of ADHD. Following this tendency, we decided to study the possible therapeutic use of caffeine in an animal model of ADHD, namely the neonatal 6-hydroxy-dopamine (6-OHDA)-lesioned rat. Therefore, at postnatal day 7 rats were lesioned at the left striatum with 6-OHDA or with saline. Thereafter, at postnatal day 25 their activity and attention were measured with the Olton maze before caffeine was administered ad libitum in the drinking water. Next, after 14 days of caffeine treatment, we repeated these measurements to assess the effect of caffeine on motor activity and attention deficit. Interestingly, while no changes in the motor activity measurements were observed before and after caffeine administration, a significant improvement in the attention deficit of the 6-OHDA lesioned rats was achieved after caffeine treatment. Thus, our results led us to hypothesize that caffeine might be useful to manage the attention deficit during the prepubertal period of ADHD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Neural Circuits via Which Single Prolonged Stress Exposure Leads to Fear Extinction Retention Deficits

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Knox, Dayan; Stanfield, Briana R.; Staib, Jennifer M.; David, Nina P.; Keller, Samantha M.; DePietro, Thomas

2016-01-01

Single prolonged stress (SPS) has been used to examine mechanisms via which stress exposure leads to post-traumatic stress disorder symptoms. SPS induces fear extinction retention deficits, but neural circuits critical for mediating these deficits are unknown. To address this gap, we examined the effect of SPS on neural activity in brain regions…

Sensory cortex underpinnings of traumatic brain injury deficits.

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Dasuni S Alwis

Full Text Available Traumatic brain injury (TBI can result in persistent sensorimotor and cognitive deficits including long-term altered sensory processing. The few animal models of sensory cortical processing effects of TBI have been limited to examination of effects immediately after TBI and only in some layers of cortex. We have now used the rat whisker tactile system and the cortex processing whisker-derived input to provide a highly detailed description of TBI-induced long-term changes in neuronal responses across the entire columnar network in primary sensory cortex. Brain injury (n=19 was induced using an impact acceleration method and sham controls received surgery only (n=15. Animals were tested in a range of sensorimotor behaviour tasks prior to and up to 6 weeks post-injury when there were still significant sensorimotor behaviour deficits. At 8-10 weeks post-trauma, in terminal experiments, extracellular recordings were obtained from barrel cortex neurons in response to whisker motion, including motion that mimicked whisker motion observed in awake animals undertaking different tasks. In cortex, there were lamina-specific neuronal response alterations that appeared to reflect local circuit changes. Hyper-excitation was found only in supragranular layers involved in intra-areal processing and long-range integration, and only for stimulation with complex, naturalistic whisker motion patterns and not for stimulation with simple trapezoidal whisker motion. Thus TBI induces long-term directional changes in integrative sensory cortical layers that depend on the complexity of the incoming sensory information. The nature of these changes allow predictions as to what types of sensory processes may be affected in TBI and contribute to post-trauma sensorimotor deficits.

Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats.

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Gehan S Georgy

Full Text Available Cerebrolysin (CBL, a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF, is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect of CBL in modulating the complications of hyperglycaemia experimentally induced by streptozotocin (STZ on the rat brain hippocampus. To this end, male adult Sprague Dawley rats were divided into (i vehicle- (ii CBL- and (iii STZ diabetic-control as well as (iv STZ+CBL groups. Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c%, which were associated by weight loss, elevated tumor necrosis factor (TNF-α and decreased insulin growth factor (IGF-1β in the serum. Uncontrolled hyperglycemia caused learning and memory impairments that corroborated degenerative changes, neuronal loss and expression of caspase (Casp-3 in the hippocampal area of STZ-diabetic rats. Behavioral deficits were associated by decreased hippocampal glutamate (GLU, glycine, serotonin (5-HT and dopamine. Moreover, diabetic rats showed an increase in hippocampal nitric oxide and thiobarbituric acid reactive substances versus decreased non-protein sulfhydryls. Though CBL did not affect STZ-induced hyperglycemia, it partly improved body weight as well as HbA1c%. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas and reduced Casp-3 expression. CBL improved serum TNF-α and IGF-1β, GLU and 5-HT as well as hampering oxidative biomarkers. In conclusion, CBL possesses neuroprotection against diabetes-associated cerebral neurodegeneration and cognitive decline via anti

Cognitive Function of Children and Adolescents with Attention Deficit Hyperactivity Disorder and Learning Difficulties: A Developmental Perspective

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Huang, Fang; Sun, Li; Qian, Ying; Liu, Lu; Ma, Quan-Gang; Yang, Li; Cheng, Jia; Cao, Qing-Jiu; Su, Yi; Gao, Qian; Wu, Zhao-Min; Li, Hai-Mei; Qian, Qiu-Jin; Wang, Yu-Feng

2016-01-01

Background: The cognitive function of children with either attention deficit hyperactivity disorder (ADHD) or learning disabilities (LDs) is known to be impaired. However, little is known about the cognitive function of children with comorbid ADHD and LD. The present study aimed to explore the cognitive function of children and adolescents with ADHD and learning difficulties in comparison with children with ADHD and healthy controls in different age groups in a large Chinese sample. Methods: Totally, 1043 participants with ADHD and learning difficulties (the ADHD + learning difficulties group), 870 with pure ADHD (the pure ADHD group), and 496 healthy controls were recruited. To investigate the difference in cognitive impairment using a developmental approach, all participants were divided into three age groups (6–8, 9–11, and 12–14 years old). Measurements were the Chinese-Wechsler Intelligence Scale for Children, the Stroop Color-Word Test, the Trail-Making Test, and the Behavior Rating Inventory of Executive Function-Parents (BRIEF). Multivariate analysis of variance was used. Results: The results showed that after controlling for the effect of ADHD symptoms, the ADHD + learning difficulties group was still significantly worse than the pure ADHD group, which was, in turn, worse than the control group on full intelligence quotient (98.66 ± 13.87 vs. 105.17 ± 14.36 vs. 112.93 ± 13.87, P ADHD symptoms, intelligence quotient, age, and gender. As for the age groups, the differences among groups became nonsignificant in the 12–14 years old group for inhibition (meaning interference of the Stroop Color-Word Test, 18.00 [13.00, 25.00] s vs. 17.00 [15.00, 26.00] s vs. 17.00 [10.50, 20.00] s, P = 0.704) and shift function (shifting time of the Trail-Making Test, 62.00 [43.00, 97.00] s vs. 53.00 [38.00, 81.00] s vs. 101.00 [88.00, 114.00] s, P = 0.778). Conclusions: Children and adolescents with ADHD and learning difficulties have more severe cognitive

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

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

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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…

Water deficit and salt stress diagnosis through LED induced chlorophyll fluorescence analysis in Jatropha curcas L. oil plants for biodiesel

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Gouveia-Neto, Artur S.; Silva, Elias A., Jr.; Oliveira, Ronaldo A.; Cunha, Patrícia C.; Costa, Ernande B.; Câmara, Terezinha J. R.; Willadino, Lilia G.

2011-02-01

Light-emitting-diode induced chlorophyll fluorescence analysis is employed to investigate the effect of water and salt stress upon the growth process of physicnut(jatropha curcas) grain oil plants for biofuel. Red(Fr) and far-red (FFr) chlorophyll fluorescence emission signals around 685 nm and 735 nm, respectively, were observed and examined as a function of the stress intensity(salt concentration and water deficit) for a period of time of 30 days. The chlorophyll fluorescence(ChlF) ratio Fr/FFr which is a valuable nondestructive and nonintrusive indicator of the chlorophyll content of leaves was exploited to monitor the level of stress experienced by the jatropha plants. The ChlF technique data indicated that salinity plays a minor role in the chlorophyll concentration of leaves tissues for NaCl concentrations in the 25 to 200 mM range, and results agreed quite well with those obtained using conventional destructive spectrophotometric methods. Nevertheless, for higher NaCl concentrations a noticeable decrease in the Chl content was observed. The Chl fluorescence ratio analysis also permitted detection of damage caused by water deficit in the early stages of the plants growing process. A significant variation of the Fr/FFr ratio was observed sample in the first 10 days of the experiment when one compared control and nonwatered samples. The results suggest that the technique may potentially be applied as an early-warning indicator of stress caused by water deficit.

Attention Deficit Disorder Comes of Age: Toward the Twenty-First Century.

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Shaywitz, Sally E., Ed.; Shaywitz, Bennett A., Ed.

This collection of papers focuses on definitions, assessment, assessment instruments, and distinctions between attention deficit disorder (ADD) and general learning disabilities or conduct disorders. Part I covers issues of definition and assessment in the following papers: "Methodological Issues in the Classification of ADD" (Jack Fletcher, et…

Genistein ameliorates learning and memory deficits in amyloid β(1-40) rat model of Alzheimer's disease.

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Bagheri, Maryam; Joghataei, Mohammad-Taghi; Mohseni, Simin; Roghani, Mehrdad

2011-03-01

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by increased β-amyloid (Aβ) deposition and neuronal dysfunction leading to impaired learning and recall. Ageing, heredity, and induced oxidative stress are among proposed risk factors. The increased frequency of the disease in women also suggests a role for estrogen in development of AD. In the present study, effects of the phytoestrogen genistein (10mg/kg) on learning and memory impairments was assessed in intrahippocampal Aβ(1-40)-injected rats. The estrogen receptor antagonist fulvestrant was injected intracerebroventricularly in a group of Aβ-lesioned rats. The Aβ-injected animals exhibited the following: lower spontaneous alternation score in Y-maze tasks, impaired retention and recall capability in the passive avoidance test, and fewer correct choices and more errors in the RAM task. Genistein, but not genistein and fulvestrant, significantly improved most of these parameters. Measurements of oxidative stress markers in hippocampal tissue of Aβ-injected rats showed an elevation of malondialdehyde (MDA) and nitrite content, and a reduction of superoxide dismutase (SOD) activity. Genistein significantly attenuated the increased MDA content but did not affect the nitrite content or SOD activity. These results indicate that genistein pretreatment ameliorates Aβ-induced impairment of short-term spatial memory in rats through an estrogenic pathway and by inducing attenuation of oxidative stress. Copyright © 2010 Elsevier Inc. All rights reserved.

Opposite monosynaptic scaling of BLP-vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory.

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Yang, Ying; Wang, Zhi-Hao; Jin, Sen; Gao, Di; Liu, Nan; Chen, Shan-Ping; Zhang, Sinan; Liu, Qing; Liu, Enjie; Wang, Xin; Liang, Xiao; Wei, Pengfei; Li, Xiaoguang; Li, Yin; Yue, Chenyu; Li, Hong-Lian; Wang, Ya-Li; Wang, Qun; Ke, Dan; Xie, Qingguo; Xu, Fuqiang; Wang, Liping; Wang, Jian-Zhi

2016-07-14

Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP-vCA1 connection. Optogenetic disruption of BLP-vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP-vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP-vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP-vCA1 controls LHF- and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory.

Opposite monosynaptic scaling of BLP–vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory

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Yang, Ying; Wang, Zhi-Hao; Jin, Sen; Gao, Di; Liu, Nan; Chen, Shan-Ping; Zhang, Sinan; Liu, Qing; Liu, Enjie; Wang, Xin; Liang, Xiao; Wei, Pengfei; Li, Xiaoguang; Li, Yin; Yue, Chenyu; Li, Hong-lian; Wang, Ya-Li; Wang, Qun; Ke, Dan; Xie, Qingguo; Xu, Fuqiang; Wang, Liping; Wang, Jian-Zhi

2016-01-01

Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP–vCA1 connection. Optogenetic disruption of BLP–vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP–vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP–vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP–vCA1 controls LHF- and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory. PMID:27411738

The Effects of Different Compatibilities of Qing'e Formula on Scopolamine?induced Learning and Memory Impairment in the Mouse

Institute of Scientific and Technical Information of China (English)

Xiao‑Ping Zheng; Fang‑Di Hu; Li Yang; Yu‑Ling Ma; Bo‑Lu Sun; Chang‑Hong Wang; Zheng‑Tao Wang

2017-01-01

Background: The Qing'e formula (QEF) is a well?known traditional Chinese prescription that has been clinically employed for treatment of bone disease for hundreds of years. Objective: The present study aims to observe the effects of different compatibilities of QEF on the scopolamine?induced learning and memory impairment in the mouse, and further to explore its action mechanisms and compatibility rationality. Materials and Methods: The learning and memory alterations in the mouse were evaluated using the step?down test and Morris water maze (MWM) test; the acetylcholinesterase (AChE) activity and brain?derived neurotrophic factor (BDNF) expression in the hippocampus were measured using colorimetric method or immunohistochemistry. Results: The results showed that different compatibilities of QEF significantly prolonged latency in the step?down test, shortened escape latency in the navigation test, increased the percentage of residence time, and the percentage of swimming distance in the target quadrant in the probe trial session. In addition, our results also found that different compatibilities of QEF remarkably inhibited AChE activity and increased BDNF expression in the hippocampus of mice. What's more, the group after being treated with whole recipe (QF) showed the highest level of improvement. Conclusions: These findings not only suggest that QEF may effectively ameliorate cognitive deficits through inhibiting AChE activity and increasing BDNF expression in the hippocampus but also elucidate the rationality of QEF.

Effect of meaning on apraxic finger imitation deficits.

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Achilles, E I S; Fink, G R; Fischer, M H; Dovern, A; Held, A; Timpert, D C; Schroeter, C; Schuetz, K; Kloetzsch, C; Weiss, P H

2016-02-01

Apraxia typically results from left-hemispheric (LH), but also from right-hemispheric (RH) stroke, and often impairs gesture imitation. Especially in LH stroke, it is important to differentiate apraxia-induced gesture imitation deficits from those due to co-morbid aphasia and associated semantic deficits, possibly influencing the imitation of meaningful (MF) gestures. To explore this issue, we first investigated if the 10 supposedly meaningless (ML) gestures of a widely used finger imitation test really carry no meaning, or if the test also contains MF gestures, by asking healthy subjects (n=45) to classify these gestures as MF or ML. Most healthy subjects (98%) classified three of the 10 gestures as clearly MF. Only two gestures were considered predominantly ML. We next assessed how imitation in stroke patients (255 LH, 113 RH stroke) is influenced by gesture meaning and how aphasia influences imitation of LH stroke patients (n=208). All patients and especially patients with imitation deficits (17% of LH, 27% of RH stroke patients) imitated MF gestures significantly better than ML gestures. Importantly, meaningfulness-scores of all 10 gestures significantly predicted imitation scores of patients with imitation deficits. Furthermore, especially in LH stroke patients with imitation deficits, the severity of aphasia significantly influenced the imitation of MF, but not ML gestures. Our findings in a large patient cohort support current cognitive models of imitation and strongly suggest that ML gestures are particularly sensitive to detect imitation deficits while minimising confounding effects of aphasia which affect the imitation of MF gestures in LH stroke patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human brain lesion-deficit inference remapped.

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Mah, Yee-Haur; Husain, Masud; Rees, Geraint; Nachev, Parashkev

2014-09-01

. Positively, we show that novel machine learning techniques employing high-dimensional inference can nonetheless accurately converge on the true locus. We conclude that current inferences about human brain function and deficits based on lesion mapping must be re-evaluated with methodology that adequately captures the high-dimensional structure of lesion data. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Blind Evaluation of Body Reflexes and Motor Skills in Learning Disability.

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Freides, David; And Others

1980-01-01

Twelve 6 to 10 year old boys with learning disability were blindly compared with paired controls on measures of postural and equilibrium reflexes as well as skills. Learning disabled children as a group showed significant deficits on all measures; a few, however, were totally without deficit. (Author/SBH)

Non-Adjacent Dependency Learning in Infants at Familial Risk of Dyslexia

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Kerkhoff, Annemarie; de Bree, Elise; de Klerk, Maartje; Wijnen, Frank

2013-01-01

This study tests the hypothesis that developmental dyslexia is (partly) caused by a deficit in implicit sequential learning, by investigating whether infants at familial risk of dyslexia can track non-adjacent dependencies in an artificial language. An implicit learning deficit would hinder detection of such dependencies, which mark grammatical…

Cannabidiol prevents motor and cognitive impairments induced by reserpine in rats

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Fernanda Fiel Peres

2016-09-01

Full Text Available Cannabidiol (CBD is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory and neuroprotective effects. In Parkinson’s disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson’s disease. The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats. Male Wistar rats received four injections of CBD (0.5 or 5 mg/kg or vehicle (days 2-5. On days 3 and 5, animals received also one injection of 1 mg/kg reserpine or vehicle. Locomotor activity, vacuous chewing movements and catalepsy were assessed from day 1 to day 7. On days 8 and 9, we evaluated animals’ performance on the plus-maze discriminative avoidance task, for learning/memory assessment. CBD (0.5 and 5 mg/kg attenuated the increase in catalepsy behavior and in oral movements – but not the decrease in locomotion – induced by reserpine. CBD (0.5 mg/kg also ameliorated the reserpine-induced memory deficit in the discriminative avoidance task. Our data show that CBD is able to attenuate motor and cognitive impairments induced by reserpine, suggesting the use of this compound in the pharmacotherapy of Parkinson’s disease and tardive dyskinesia.

Traumatic brain injury and obesity induce persistent central insulin resistance.

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Karelina, Kate; Sarac, Benjamin; Freeman, Lindsey M; Gaier, Kristopher R; Weil, Zachary M

2016-04-01

Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Cognitive Deficits as a Mediator of Poor Occupational Function in Remitted Major Depressive Disorder Patients

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Woo, Young Sup; Rosenblat, Joshua D.; Kakar, Ron; Bahk, Won-Myong; McIntyre, Roger S.

2016-01-01

Cognitive deficits in major depressive disorder (MDD) patients have been described in numerous studies. However, few reports have aimed to describe cognitive deficits in the remitted state of MDD and the mediational effect of cognitive deficits on occupational outcome. The aim of the current review is to synthesize the literature on the mediating and moderating effects of specific domains of cognition on occupational impairment among people with remitted MDD. In addition, predictors of cognitive deficits found to be vocationally important will be examined. Upon examination of the extant literature, attention, executive function and verbal memory are areas of consistent impairment in remitted MDD patients. Cognitive domains shown to have considerable impact on vocational functioning include deficits in memory, attention, learning and executive function. Factors that adversely affect cognitive function related to occupational accommodation include higher age, late age at onset, residual depressive symptoms, history of melancholic/psychotic depression, and physical/psychiatric comorbidity, whereas higher levels of education showed a protective effect against cognitive deficit. Cognitive deficits are a principal mediator of occupational impairment in remitted MDD patients. Therapeutic interventions specifically targeting cognitive deficits in MDD are needed, even in the remitted state, to improve functional recovery, especially in patients who have a higher risk of cognitive deficit. PMID:26792035

Low dopamine D5 receptor density in hippocampus in an animal model of attention-deficit/hyperactivity disorder (ADHD)

DEFF Research Database (Denmark)

Medin, T; Rinholm, J E; Owe, S G

2013-01-01

A state of low dopaminergic activity has been implicated in attention-deficit/hyperactivity disorder (ADHD). The clinical symptoms of ADHD include inattention, impulsivity and hyperactivity, as well as impaired learning; dopaminergic modulation of the functions in the hippocampus is important......, indicating a reduced reservoir for insertion of receptors into the plasma membrane. DRs are important for long-term potentiation and long-term depression, hence the deficit may contribute to the learning difficulties in individuals with the diagnosis of ADHD....... to both learning and memory. To determine dopamine receptor (DR) density in a well-established animal model for ADHD, we quantified the dopamine D5 receptors in the hippocampus in the spontaneously hypertensive rat. We used immunofluorescence microscopy and immunogold electron microscopy to quantify...

Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats

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Yu, Yu-Wen; Hsieh, Tsung-Hsun; Chen, Kai-Yun; Wu, John Chung-Che; Hoffer, Barry J.; Greig, Nigel H.; Li, Yazhou; Lai, Jing-Huei; Chang, Cheng-Fu; Lin, Jia-Wei; Chen, Yu-Hsin

2016-01-01

Abstract Mild traumatic brain injury (mTBI) is a major public health issue, representing 75–90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13–15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment. PMID:26972789

Curcumin exerts neuroprotective effects against homocysteine intracerebroventricular injection-induced cognitive impairment and oxidative stress in rat brain.

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Ataie, Amin; Sabetkasaei, Masoumeh; Haghparast, Abbas; Moghaddam, Akbar Hajizadeh; Ataee, Ramin; Moghaddam, Shiva Nasiraei

2010-08-01

Aging is the major risk factor for neurodegenerative diseases and oxidative stress and is involved in their pathophysiology. Oxidative stress can induce neuronal damage and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. In this study we investigated the neuroprotective properties of the natural polyphenolic antioxidant compound, curcumin, against homocysteine (Hcy) neurotoxicity. Curcumin (5, 15, or 45 mg/kg) was injected intraperitoneally once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 micromol/microl) intracerebroventricular injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests, were evaluated 24 hours after the last injection of curcumin or vehicle. Results indicated that Hcy induces lipid peroxidation and increases malondialdehyde (MDA) and superoxide anion (SOA) levels in whole rat brain. In addition, Hcy impaired memory retention in the passive avoidance learning test. However, curcumin treatment significantly decreased MDA and SOA levels and improved learning and memory in rats. These results suggest that Hcy may induce lipid peroxidation in rat brain and that polyphenol treatment (curcumin) improves learning and memory deficits by protecting the nervous system against oxidative stress.

Activation of dopamine D3 receptors inhibits reward-related learning induced by cocaine.

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Kong, H; Kuang, W; Li, S; Xu, M

2011-03-10

Memories of learned associations between the rewarding properties of drugs and environmental cues contribute to craving and relapse in humans. The mesocorticolimbic dopamine (DA) system is involved in reward-related learning induced by drugs of abuse. DA D3 receptors are preferentially expressed in mesocorticolimbic DA projection areas. Genetic and pharmacological studies have shown that DA D3 receptors suppress locomotor-stimulant effects of cocaine and reinstatement of cocaine-seeking behaviors. Activation of the extracellular signal-regulated kinase (ERK) induced by acute cocaine administration is also inhibited by D3 receptors. How D3 receptors modulate cocaine-induced reward-related learning and associated changes in cell signaling in reward circuits in the brain, however, have not been fully investigated. In the present study, we show that D3 receptor mutant mice exhibit potentiated acquisition of conditioned place preference (CPP) at low doses of cocaine compared to wild-type mice. Activation of ERK and CaMKIIα, but not the c-Jun N-terminal kinase and p38, in the nucleus accumbens, amygdala and prefrontal cortex is also potentiated in D3 receptor mutant mice compared to that in wild-type mice following CPP expression. These results support a model in which D3 receptors modulate reward-related learning induced by low doses of cocaine by inhibiting activation of ERK and CaMKIIα in reward circuits in the brain. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Abnormal emotional learning in a rat model of autism exposed to valproic acid in utero

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Anwesha eBanerjee

2014-11-01

Full Text Available Autism Spectrum Disorders (ASD are complex neurodevelopmental disorders characterized by repetitive behavior and impaired social communication and interactions. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety and some ASD individuals exhibit impaired emotional learning. We therefore sought to further examine anxiety and emotional learning in an environmentally induced animal model of ASD that utilizes the administration of the known teratogen, valproic acid (VPA during gestation. Specifically we exposed dams to one of two different doses of VPA (500 and 600 mg/kg or vehicle on day 12.5 of gestation and examined the resultant progeny. Our data indicate that animals exposed to VPA in utero exhibit enhanced anxiety in the open field test and normal object recognition memory compared to control animals. Animals exposed to 500 mg/kg of VPA displayed normal acquisition of auditory fear conditioning, and exhibited reduced extinction of fear memory and normal litter survival rates as compared to control animals. We observed that animals exposed to 600 mg/kg of VPA exhibited a significant reduction in the acquisition of fear conditioning, a significant reduction in social interaction and a significant reduction in litter survival rates as compared to control animals. VPA (600 mg/kg exposed animals exhibited similar shock sensitivity and hearing as compared to control animals indicating the fear conditioning deficit observed in these animals was not likely due to sensory deficits, but rather due to deficits in learning or memory retrieval. In conclusion, considering that progeny from dams exposed to rather similar doses of VPA exhibit striking differences in emotional learning, the VPA model may serve as a useful tool to explore the molecular and cellular mechanisms that contribute to not only ASD, but also emotional learning.

Role of the area postrema in radiation-induced taste aversion learning and emesis in cats

International Nuclear Information System (INIS)

Rabin, B.M.; Hunt, W.A.; Chedester, A.L.; Lee, J.

1986-01-01

The role of the area postrema in radiation-induced emesis and taste aversion learning and the relationship between these behaviors were studied in cats. The potential involvement of neural factors which might be independent of the area postrema was minimized by using low levels of ionizing radiation (100 rads at a dose rate of 40 rads/min) to elicit a taste aversion, and by using body-only exposures (4500 and 6000 rads at 450 rads/min) to produce emesis. Lesions of the area postrema disrupted both taste aversion learning and emesis following irradiation. These results, which indicate that the area postrema is involved in the mediation of both radiation-induced emesis and taste aversion learning in cats under these experimental conditions, are interpreted as being consistent with the hypotheses that similar mechanisms mediate both responses to exposure to ionizing radiation, and that the taste aversion learning paradigm can therefore serve as a model system for studying radiation-induced emesis

Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

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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

Purple sweet potato color attenuates domoic acid-induced cognitive deficits by promoting estrogen receptor-α-mediated mitochondrial biogenesis signaling in mice.

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Lu, Jun; Wu, Dong-Mei; Zheng, Yuan-Lin; Hu, Bin; Cheng, Wei; Zhang, Zi-Feng

2012-02-01

Recent findings suggest that endoplasmic reticulum stress may be involved in the pathogenesis of domoic acid-induced neurodegeneration. Purple sweet potato color, a class of naturally occurring anthocyanins, has beneficial health and biological effects. Recent studies have also shown that anthocyanins have estrogenic activity and can enhance estrogen receptor-α expression. In this study, we evaluated the effect of purple sweet potato color on cognitive deficits induced by hippocampal mitochondrial dysfunction in domoic acid-treated mice and explored the potential mechanisms underlying this effect. Our results showed that the oral administration of purple sweet potato color to domoic acid-treated mice significantly improved their behavioral performance in a step-through passive avoidance task and a Morris water maze task. These improvements were mediated, at least in part, by a stimulation of estrogen receptor-α-mediated mitochondrial biogenesis signaling and by decreases in the expression of p47phox and gp91phox. Decreases in reactive oxygen species and protein carbonylation were also observed, along with a blockade of the endoplasmic reticulum stress pathway. Furthermore, purple sweet potato color significantly suppressed endoplasmic reticulum stress-induced apoptosis, which prevented neuron loss and restored the expression of memory-related proteins. However, knockdown of estrogen receptor-α using short hairpin RNA only partially blocked the neuroprotective effects of purple sweet potato color in the hippocampus of mice cotreated with purple sweet potato color and domoic acid, indicating that purple sweet potato color acts through multiple pathways. These results suggest that purple sweet potato color could be a possible candidate for the prevention and treatment of cognitive deficits in excitotoxic and other brain disorders. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Reversal of Stress-Induced Social Interaction Deficits by Buprenorphine.

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Browne, Caroline A; Falcon, Edgardo; Robinson, Shivon A; Berton, Olivier; Lucki, Irwin

2018-02-01

Patients with post-traumatic stress disorder frequently report persistent problems with social interactions, emerging after a traumatic experience. Chronic social defeat stress is a widely used rodent model of stress that produces robust and sustained social avoidance behavior. The avoidance of other rodents can be reversed by 28 days of treatment with selective serotonin reuptake inhibitors, the only pharmaceutical class approved by the U.S. Food and Drug Administration for treating post-traumatic stress disorder. In this study, the sensitivity of social interaction deficits evoked by 10 days of chronic social defeat stress to prospective treatments for post-traumatic stress disorder was examined. The effects of acute and repeated treatment with a low dose of buprenorphine (0.25 mg/kg/d) on social interaction deficits in male C57BL/6 mice by chronic social defeat stress were studied. Another cohort of mice was used to determine the effects of the selective serotonin reuptake inhibitor fluoxetine (10 mg/kg/d), the NMDA antagonist ketamine (10 mg/kg/d), and the selective kappa opioid receptor antagonist CERC-501 (1 mg/kg/d). Changes in mRNA expression of Oprm1 and Oprk1 were assessed in a separate cohort. Buprenorphine significantly reversed social interaction deficits produced by chronic social defeat stress following 7 days of administration, but not after acute injection. Treatment with fluoxetine for 7 days, but not 24 hours, also reinstated social interaction behavior in mice that were susceptible to chronic social defeat. In contrast, CERC-501 and ketamine failed to reverse social avoidance. Gene expression analysis found: (1) Oprm1 mRNA expression was reduced in the hippocampus and increased in the frontal cortex of susceptible mice and (2) Oprk1 mRNA expression was reduced in the amygdala and increased in the frontal cortex of susceptible mice compared to non-stressed controls and stress-resilient mice. Short-term treatment with buprenorphine and fluoxetine

Effects of voluntary and treadmill exercise on spontaneous withdrawal signs, cognitive deficits and alterations in apoptosis-associated proteins in morphine-dependent rats.

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Mokhtari-Zaer, Amin; Ghodrati-Jaldbakhan, Shahrbanoo; Vafaei, Abbas Ali; Miladi-Gorji, Hossein; Akhavan, Maziar M; Bandegi, Ahmad Reza; Rashidy-Pour, Ali

2014-09-01

Chronic exposure to morphine results in cognitive deficits and alterations of apoptotic proteins in favor of cell death in the hippocampus, a brain region critically involved in learning and memory. Physical activity has been shown to have beneficial effects on brain health. In the current work, we examined the effects of voluntary and treadmill exercise on spontaneous withdrawal signs, the associated cognitive defects, and changes of apoptotic proteins in morphine-dependent rats. Morphine dependence was induced through bi-daily administrations of morphine (10mg/kg) for 10 days. Then, the rats were trained under two different exercise protocols: mild treadmill exercise or voluntary wheel exercise for 10 days. After exercise training, their spatial learning and memory and aversive memory were examined by a water maze and by an inhibitory avoidance task, respectively. The expression of the pro-apoptotic protein Bax and the anti-apoptotic protein Bcl-2 in the hippocampus were determined by immunoblotting. We found that chronic exposure to morphine impaired spatial and aversive memory and remarkably suppressed the expression of Bcl-2, but Bax expression remained constant. Both voluntary and treadmill exercise alleviated memory impairment, increased the expression of Bcl-2 protein, and only the later suppressed the expression of Bax protein in morphine-dependent animals. Moreover, both exercise protocols diminished the occurrence of spontaneous morphine withdrawal signs. Our findings showed that exercise reduces the spontaneous morphine-withdrawal signs, blocks the associated impairment of cognitive performance, and overcomes morphine-induced alterations in apoptotic proteins in favor of cell death. Thus, exercise may be a useful therapeutic strategy for cognitive and behavioral deficits in addict individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

Cognitive deficits develop 1month after diffuse brain injury and are exaggerated by microglia-associated reactivity to peripheral immune challenge.

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Muccigrosso, Megan M; Ford, Joni; Benner, Brooke; Moussa, Daniel; Burnsides, Christopher; Fenn, Ashley M; Popovich, Phillip G; Lifshitz, Jonathan; Walker, Fredrick Rohan; Eiferman, Daniel S; Godbout, Jonathan P

2016-05-01

Traumatic brain injury (TBI) elicits immediate neuroinflammatory events that contribute to acute cognitive, motor, and affective disturbance. Despite resolution of these acute complications, significant neuropsychiatric and cognitive issues can develop and progress after TBI. We and others have provided novel evidence that these complications are potentiated by repeated injuries, immune challenges and stressors. A key component to this may be increased sensitization or priming of glia after TBI. Therefore, our objectives were to determine the degree to which cognitive deterioration occurred after diffuse TBI (moderate midline fluid percussion injury) and ascertain if glial reactivity induced by an acute immune challenge potentiated cognitive decline 30 days post injury (dpi). In post-recovery assessments, hippocampal-dependent learning and memory recall were normal 7 dpi, but anterograde learning was impaired by 30 dpi. Examination of mRNA and morphological profiles of glia 30 dpi indicated a low but persistent level of inflammation with elevated expression of GFAP and IL-1β in astrocytes and MHCII and IL-1β in microglia. Moreover, an acute immune challenge 30 dpi robustly interrupted memory consolidation specifically in TBI mice. These deficits were associated with exaggerated microglia-mediated inflammation with amplified (IL-1β, CCL2, TNFα) and prolonged (TNFα) cytokine/chemokine expression, and a marked reactive morphological profile of microglia in the CA3 of the hippocampus. Collectively, these data indicate that microglia remain sensitized 30 dpi after moderate TBI and a secondary inflammatory challenge elicits robust microglial reactivity that augments cognitive decline. Traumatic brain injury (TBI) is a major risk factor in development of neuropsychiatric problems long after injury, negatively affecting quality of life. Mounting evidence indicates that inflammatory processes worsen with time after a brain injury and are likely mediated by glia. Here

The mouse beam walking assay offers improved sensitivity over the mouse rotarod in determining motor coordination deficits induced by benzodiazepines.

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Stanley, Joanna L; Lincoln, Rachael J; Brown, Terry A; McDonald, Louise M; Dawson, Gerard R; Reynolds, David S

2005-05-01

The mouse rotarod test of motor coordination/sedation is commonly used to predict clinical sedation caused by novel drugs. However, past experience suggests that it lacks the desired degree of sensitivity to be predictive of effects in humans. For example, the benzodiazepine, bretazenil, showed little impairment of mouse rotarod performance, but marked sedation in humans. The aim of the present study was to assess whether the mouse beam walking assay demonstrates: (i) an increased sensitivity over the rotarod and (ii) an increased ability to predict clinically sedative doses of benzodiazepines. The study compared the effects of the full benzodiazepine agonists, diazepam and lorazepam, and the partial agonist, bretazenil, on the mouse rotarod and beam walking assays. Diazepam and lorazepam significantly impaired rotarod performance, although relatively high GABA-A receptor occupancy was required (72% and 93%, respectively), whereas beam walking performance was significantly affected at approximately 30% receptor occupancy. Bretazenil produced significant deficits at 90% and 53% receptor occupancy on the rotarod and beam walking assays, respectively. The results suggest that the mouse beam walking assay is a more sensitive tool for determining benzodiazepine-induced motor coordination deficits than the rotarod. Furthermore, the GABA-A receptor occupancy values at which significant deficits were determined in the beam walking assay are comparable with those observed in clinical positron emission tomography studies using sedative doses of benzodiazepines. These data suggest that the beam walking assay may be able to more accurately predict the clinically sedative doses of novel benzodiazepine-like drugs.

Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration.

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McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

2011-08-01

Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a "challenge" high-dose METH regimen when administered at PND90. Mechanisms underlying this "resistance" were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity. Copyright © 2011 Wiley-Liss, Inc.

Amyloid-β Homeostasis Bridges Inflammation, Synaptic Plasticity Deficits and Cognitive Dysfunction in Multiple Sclerosis.

Science.gov (United States)

Stampanoni Bassi, Mario; Garofalo, Sara; Marfia, Girolama A; Gilio, Luana; Simonelli, Ilaria; Finardi, Annamaria; Furlan, Roberto; Sancesario, Giulia M; Di Giandomenico, Jonny; Storto, Marianna; Mori, Francesco; Centonze, Diego; Iezzi, Ennio

2017-01-01

Cognitive deficits are frequently observed in multiple sclerosis (MS), mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity occurring within hippocampal structures is considered as one of the basic physiological mechanisms of learning and memory. In experimental models of MS, hippocampal plasticity is profoundly altered by proinflammatory cytokines. Although mechanisms of inflammation-induced hippocampal pathology in MS are not completely understood, alteration of Amyloid-β (Aβ) metabolism is emerging as a key factor linking together inflammation, synaptic plasticity and neurodegeneration in different neurological diseases. We explored the correlation between concentrations of Aβ 1-42 and the levels of some proinflammatory and anti-inflammatory cytokines (interleukin-1β (IL-1β), IL1-ra, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα), interferon γ (IFNγ)) in the cerebrospinal fluid (CSF) of 103 remitting MS patients. CSF levels of Aβ 1-42 were negatively correlated with the proinflammatory cytokine IL-8 and positively correlated with the anti-inflammatory molecules IL-10 and interleukin-1 receptor antagonist (IL-1ra). Other correlations, although noticeable, were either borderline or not significant. Our data show that an imbalance between proinflammatory and anti-inflammatory cytokines may lead to altered Aβ homeostasis, representing a key factor linking together inflammation, synaptic plasticity and cognitive dysfunction in MS. This could be relevant to identify novel therapeutic approaches to hinder the progression of cognitive dysfunction in MS.

Amyloid-β Homeostasis Bridges Inflammation, Synaptic Plasticity Deficits and Cognitive Dysfunction in Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Mario Stampanoni Bassi

2017-11-01