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Sample records for hippocampus preventive effect

  1. Effects of estrogen in preventing neuronal insulin resistance in hippocampus of obese rats are different between genders.

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    Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2011-11-07

    The effects of estrogen on the prevention of impaired insulin-induced long-term depression in the hippocampus and neuronal insulin signaling caused by high-fat diet (HF) were studied in male and female rats. Both male and female rats were fed with a normal diet (ND; 19.7% energy from fat) or a high-fat diet (HF; 59.3% energy from fat) for 12 weeks. Then, rats were divided into four subgroups: ND, ND+E, HF and HF+E. The subgroups with+E were given 50 μg/kg estrogen subcutaneously once a day for 30 days. At the end of the experimental period, blood and brain samples were collected to determine the peripheral insulin resistance and neuronal insulin resistance, respectively. Both male and female rats fed with HF developed peripheral insulin resistance as indicated by increased body weight, visceral fat, plasma insulin and HOMA index. Estrogen administration decreased those parameters, indicating improved peripheral insulin sensitivity, in both male and female HF rats. HF diet consumption also caused impaired insulin-induced long-term depression in hippocampus and impaired neuronal insulin receptor function and signaling, indicating neuronal insulin resistance, in both male and female rats. Estrogen treatment could attenuate these neuronal impairments only in HF female rats. The activation of the estrogen pathway could preserve insulin sensitivity in the peripheral tissue in both male and female rats. In neuronal tissue, however, the benefit of estrogen could be found only in female rats. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Effects of glucocorticoids on mood, memory, and the hippocampus. Treatment and preventive therapy.

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    Brown, E Sherwood

    2009-10-01

    Corticosteroids, such as prednisone and dexamethasone, are commonly prescribed medications that suppress the immune system and decrease inflammation. Common side effects of long-term treatment with corticosteroids include weight gain, osteoporosis, and diabetes mellitus. This paper reviews the literature on psychiatric and cognitive changes during corticosteroid therapy and potential treatment options. Hypomania and mania are the most common mood changes during acute corticosteroid therapy, although depression has also been reported. However, depression is reported to be more common than mania during long-term treatment with corticosteroids. A decline in declarative and working memory is also reported during corticosteroid therapy. Corticosteroids are associated with changes in the temporal lobe, detected by structural, functional, and spectroscopic imaging. The mood and cognitive symptoms are dose dependent and frequently occur during the first few weeks of therapy. Other risk factors are not well characterized. Controlled trials suggest that lithium and phenytoin can prevent mood symptoms associated with corticosteroids. Lamotrigine and memantine also have been shown to reverse, at least partially, the declarative memory effects of corticosteroids. Uncontrolled trials suggest that antipsychotics, anti-seizure medications, and perhaps some antidepressants can also be useful for normalizing mood changes associated with corticosteroids. Thus, both the symptoms and treatment response are similar to those of bipolar disorder. Moreover, corticosteroid-induced mood and cognitive alterations have been shown to be reversible with dose reduction or discontinuation of treatment.

  3. Neurogenic Effects of Ghrelin on the Hippocampus.

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    Kim, Chanyang; Kim, Sehee; Park, Seungjoon

    2017-03-08

    Mammalian neurogenesis continues throughout adulthood in the subventricular zone of the lateral ventricle and in the subgranular zone of the dentate gyrus in the hippocampus. It is well known that hippocampal neurogenesis is essential in mediating hippocampus-dependent learning and memory. Ghrelin, a peptide hormone mainly synthesized in the stomach, has been shown to play a major role in the regulation of energy metabolism. A plethora of evidence indicates that ghrelin can also exert important effects on neurogenesis in the hippocampus of the adult brain. The aim of this review is to discuss the current role of ghrelin on the in vivo and in vitro regulation of neurogenesis in the adult hippocampus. We will also discuss the possible role of ghrelin in dietary restriction-induced hippocampal neurogenesis and the link between ghrelin-induced hippocampal neurogenesis and cognitive functions.

  4. Mate Tea Prevents Oxidative Stress in the Blood and Hippocampus of Rats with Acute or Chronic Ethanol Administration

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    Bianca Scolaro

    2012-01-01

    Full Text Available Objective. The aim of this study was to evaluate the influence of acute and chronic intake of mate tea on the effects elicited by acute and chronic administration of ethanol. Methods. Oxidative stress was evaluated by measuring thiobarbituric acid-reactive substances (TBARS, as well as the activities of the antioxidant enzymes, catalase (CAT, glutathione peroxidase (GSH-Px, and superoxide dismutase (SOD in the hippocampus and blood of rats. Male Wistar rats were randomly assigned to four groups, for both acute and chronic treatment: (1 control group, (2 treated group, (3 intoxicated group, (4 and intoxicated group treated with mate tea. Results. Both ethanol administrations significantly increased TBARS in plasma and hippocampus of rats and altered antioxidant enzyme activities, changes which were reverted by mate tea administration. Conclusions. Data indicate that acute and chronic ethanol administration induced oxidative stress in hippocampus and blood and that mate tea treatment was able to prevent this situation.

  5. Gastrin-releasing peptide facilitates glutamatergic transmission in the hippocampus and effectively prevents vascular dementia induced cognitive and synaptic plasticity deficits.

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    Yang, Jiajia; Yao, Yang; Wang, Ling; Yang, Chunxiao; Wang, Faqi; Guo, Jie; Wang, Zhiyun; Yang, Zhuo; Ming, Dong

    2017-01-01

    Neuronal gastrin-releasing peptide (GRP) has been proved to be an important neuromodulator in the brain and involved in a variety of neurological diseases. Whether GRP could attenuate cognition impairment induced by vascular dementia (VD) in rats, and the mechanism of synaptic plasticity and GRP's action on synaptic efficiency are still poorly understood. In this study, we first investigated the effects of GRP on glutamatergic transmission with patch-clamp recording. We found that acute application of GRP enhanced the excitatory synaptic transmission in hippocampal CA1 neurons via GRPR in a presynaptic mechanism. Secondly, we examined whether exogenous GRP or its analogue neuromedin B (NMB) could prevent VD-induced cognitive deficits and the mechanism of synaptic plasticity. By using Morris water maze, long-term potentiation (LTP) recording, western blot assay and immunofluorescent staining, we verified for the first time that GRP or NMB substantially improved the spatial learning and memory abilities in VD rats, restored the impaired synaptic plasticity and was able to elevate the expression of synaptic proteins, synaptophysin (SYP) and CaMKII, which play pivotal roles in synaptic plasticity. These results suggest that the facilitatory effects of GRP on glutamate release may contribute to its long-term action on synaptic efficacy which is essential in cognitive function. Our findings present a new entry point for a better understanding of physiological function of GRP and raise the possibility that GRPR agonists might ameliorate cognitive deficits associated with neurological diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Electroconvulsive stimulations prevent stress-induced morphological changes in the hippocampus

    DEFF Research Database (Denmark)

    Hageman, I; Nielsen, M; Wörtwein, Gitta

    2008-01-01

    pathophysiological events contribute to the shrinkage phenomenon. Animal studies have shown that various stress paradigms can induce dendritic retraction in the CA3 pyramidal neurons of the hippocampus. Since electroconvulsive treatment is the most effective treatment in humans with major depression, we investigated...

  7. Treadmill running prevents age-related memory deficit and alters neurotrophic factors and oxidative damage in the hippocampus of Wistar rats.

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    Vanzella, Cláudia; Neves, Juliana Dalibor; Vizuete, Adriana Fernanda; Aristimunha, Dirceu; Kolling, Janaína; Longoni, Aline; Gonçalves, Carlos Alberto Saraiva; Wyse, Angela T S; Netto, Carlos Alexandre

    2017-09-15

    Clinical and pre-clinical studies indicate that exercise is beneficial to many aspects of brain function especially during aging. The present study investigated the effects of a treadmill running protocol in young (3month-old) and aged (22month-old) male Wistar rats, on: I) cognitive function, as assessed by spatial reference memory in the Morris water maze; II) oxidative stress parameters and the expression of neurotrophic factors BDNF, NT-3, IGF-1 and VEGF in the hippocampus. Animals of both ages were assigned to sedentary (non-exercised) and exercised (20min of daily running sessions, 3 times per week for 4weeks) groups. Cognition was assessed by a reference memory task run in the Morris water maze; twenty four hours after last session of behavioral testing hippocampi were collected for biochemical analysis. Results demonstrate that the moderate treadmill running exercise: I) prevented age-related deficits in reference memory in the Morris water maze; II) prevented the age-related increase of reactive oxygen species levels and lipid peroxidation in the hippocampus; III) caused an increase of BDNF, NT-3 and IGF-1 expression in the hippocampus of aged rats. Taken together, results suggest that both exercise molecular effects, namely the reduction of oxidative stress and the increase of neurotrophic factors expression in the hippocampus, might be related to its positive effect on memory performance in aged rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Nicotine-prevented learning and memory impairment in REM sleep-deprived rat is modulated by DREAM protein in the hippocampus.

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    Abd Rashid, Norlinda; Hapidin, Hermizi; Abdullah, Hasmah; Ismail, Zalina; Long, Idris

    2017-06-01

    REM sleep deprivation is associated with impairment in learning and memory, and nicotine treatment has been shown to attenuate this effect. Recent studies have demonstrated the importance of DREAM protein in learning and memory processes. This study investigates the association of DREAM protein in REM sleep-deprived rats hippocampus upon nicotine treatment. Male Sprague Dawley rats were subjected to normal condition, REM sleep deprivation and control wide platform condition for 72 hr. During this procedure, saline or nicotine (1 mg/kg) was given subcutaneously twice a day. Then, Morris water maze (MWM) test was used to assess learning and memory performance of the rats. The rats were sacrificed and the brain was harvested for immunohistochemistry and Western blot analysis. MWM test found that REM sleep deprivation significantly impaired learning and memory performance without defect in locomotor function associated with a significant increase in hippocampus DREAM protein expression in CA1, CA2, CA3, and DG regions and the mean relative level of DREAM protein compared to other experimental groups. Treatment with acute nicotine significantly prevented these effects and decreased expression of DREAM protein in all the hippocampus regions but only slightly reduce the mean relative level of DREAM protein. This study suggests that changes in DREAM protein expression in CA1, CA2, CA3, and DG regions of rat's hippocampus and mean relative level of DREAM protein may involve in the mechanism of nicotine treatment-prevented REM sleep deprivation-induced learning and memory impairment in rats.

  9. Effect of berberin on the regulatin of GFAP+ astrecyte in the hippocampus of STZ diabetic rats

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    Hamid Kalalian-Moghaddam

    2015-05-01

    Full Text Available Background: Diabetes mellitus increases the risk of central nervous system (CNS disorders such as stroke, seizures, dementia, and cognitive impairment. Berberine, a natural isoquinolne alkaloid, is reported to exhibit beneficial effect in various neurodegenerative and neuropsychiatric disorders. Moreover astrocytes are proving critical for normal CNS function, and alterations in their activity and impaired oxidative stress could contribute to diabetes-related cognitive dysfunction. Metabolic and oxidative insults often cause rapid changes in glial cells. Key indicators of this response are increased synthesis of glial fibrillary acidic protein (GFAP as an astrocytic marker. Therefore, this study was conducted to determine the effect of berberine on glial reactivity of hippocampus in (STZ-induced diabetes rats. Materials and Methods: Experimental groups included: The control, control berberine treated (100 mg/kg.8 weeks, diabetic and diabetic berberine treated (50,100 mg/kg for 8 weeks groups. The effects of berberine on glial reactivity of hippocampus evaluated in (STZ-induced diabetics rats, using GFAP immunohistochemistry test. Data were analyzed by using Prism-5, one way ANOVA and Tukey tests. Results: Eight weeks after diabetes induction we observed an increase in GFAP immune staining in the hippocampus of STZ-diabetic rats relative to levels in the control brains. In contrast, chronic treatment with berberine (50 and 100 mg/kg, p.o., once daily lowered hyperglycemia, and prevents the up regulation of GFAP in brain of diabetic rats. Conclusion: the present study demonstrates treatment with berberine resulted in an obvious reduction of GFAP+ immunoreactive astrocytes in hippocampus of STZ -induced diabetic rats.

  10. Caffeine consumption prevents diabetes-induced memory impairment and synaptotoxicity in the hippocampus of NONcZNO10/LTJ mice.

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    Duarte, João M N; Agostinho, Paula M; Carvalho, Rui A; Cunha, Rodrigo A

    2012-01-01

    Diabetic conditions are associated with modified brain function, namely with cognitive deficits, through largely undetermined processes. More than understanding the underlying mechanism, it is important to devise novel strategies to alleviate diabetes-induced cognitive deficits. Caffeine (a mixed antagonist of adenosine A(1) and A(2A) receptors) emerges as a promising candidate since caffeine consumption reduces the risk of diabetes and effectively prevents memory deficits caused by different noxious stimuli. Thus, we took advantage of a novel animal model of type 2 diabetes to investigate the behavioural, neurochemical and morphological modifications present in the hippocampus and tested if caffeine consumption might prevent these changes. We used a model closely mimicking the human type 2 diabetes condition, NONcNZO10/LtJ mice, which become diabetic at 7-11 months when kept under an 11% fat diet. Caffeine (1 g/l) was applied in the drinking water from 7 months onwards. Diabetic mice displayed a decreased spontaneous alternation in the Y-maze accompanied by a decreased density of nerve terminal markers (synaptophysin, SNAP25), mainly glutamatergic (vesicular glutamate transporters), and increased astrogliosis (GFAP immunoreactivity) compared to their wild type littermates kept under the same diet. Furthermore, diabetic mice displayed up-regulated A(2A) receptors and down-regulated A(1) receptors in the hippocampus. Caffeine consumption restored memory performance and abrogated the diabetes-induced loss of nerve terminals and astrogliosis. These results provide the first evidence that type 2 diabetic mice display a loss of nerve terminal markers and astrogliosis, which is associated with memory impairment; furthermore, caffeine consumption prevents synaptic dysfunction and astrogliosis as well as memory impairment in type 2 diabetes.

  11. Caffeine consumption prevents diabetes-induced memory impairment and synaptotoxicity in the hippocampus of NONcZNO10/LTJ mice.

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    João M N Duarte

    Full Text Available Diabetic conditions are associated with modified brain function, namely with cognitive deficits, through largely undetermined processes. More than understanding the underlying mechanism, it is important to devise novel strategies to alleviate diabetes-induced cognitive deficits. Caffeine (a mixed antagonist of adenosine A(1 and A(2A receptors emerges as a promising candidate since caffeine consumption reduces the risk of diabetes and effectively prevents memory deficits caused by different noxious stimuli. Thus, we took advantage of a novel animal model of type 2 diabetes to investigate the behavioural, neurochemical and morphological modifications present in the hippocampus and tested if caffeine consumption might prevent these changes. We used a model closely mimicking the human type 2 diabetes condition, NONcNZO10/LtJ mice, which become diabetic at 7-11 months when kept under an 11% fat diet. Caffeine (1 g/l was applied in the drinking water from 7 months onwards. Diabetic mice displayed a decreased spontaneous alternation in the Y-maze accompanied by a decreased density of nerve terminal markers (synaptophysin, SNAP25, mainly glutamatergic (vesicular glutamate transporters, and increased astrogliosis (GFAP immunoreactivity compared to their wild type littermates kept under the same diet. Furthermore, diabetic mice displayed up-regulated A(2A receptors and down-regulated A(1 receptors in the hippocampus. Caffeine consumption restored memory performance and abrogated the diabetes-induced loss of nerve terminals and astrogliosis. These results provide the first evidence that type 2 diabetic mice display a loss of nerve terminal markers and astrogliosis, which is associated with memory impairment; furthermore, caffeine consumption prevents synaptic dysfunction and astrogliosis as well as memory impairment in type 2 diabetes.

  12. Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex

    National Research Council Canada - National Science Library

    McEwen, Bruce S; Nasca, Carla; Gray, Jason D

    2016-01-01

    The hippocampus provided the gateway into much of what we have learned about stress and brain structural and functional plasticity, and this initial focus has expanded to other interconnected brain...

  13. [Correlations between hippocampus function and stressed learning and their effect on cerebro-visceral regulation processes].

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    Hecht, K; Hai, N V; Hecht, T; Moritz, V; Woossmann, H

    1976-01-01

    43 male albino rats were investigated to find out what are the effects of bilateral exclusion of pes hippocampus structures upon the development of arterial hypertension released by learning stress exposure. The following results were obtained: 5 weeks of stress exposure (learning load and heavy learning load) caused disturbances of information-processing events of the central nervous system in all the animals with hippocampal lesions. Systolic blood pressure values, fasting blood sugar values, and adrenal weights fall within the physiological range. The B-cells of the pancreatic islets show hypergranulation. Functional tests of the blood pressure under exercise load, and of blood sugar under glucose load revealed normal reactions in animals with hippocampal lesions. In animals with intact brains the same stress exposure caused pathologic malfunctioning (under learning stress) or even premorbid states. The results being considered in relation to the pathogenesis of arterial hypertension show that the exclusion of circumscribed areas of the hippocampus prevents the development of permanent, stress-induced emotional excitations spreading into the viscerum.

  14. Stress Effects on the Hippocampus: A Critical Review

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    Kim, Eun Joo; Pellman, Blake; Kim, Jeansok J.

    2015-01-01

    Uncontrollable stress has been recognized to influence the hippocampus at various levels of analysis. Behaviorally, human and animal studies have found that stress generally impairs various hippocampal-dependent memory tasks. Neurally, animal studies have revealed that stress alters ensuing synaptic plasticity and firing properties of hippocampal…

  15. [Effect of tongluo xingnao effervescent tablet on learning and memory of AD rats and expression of insulin-degrading enzyme in hippocampus].

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    Zhang, Yin-Jie; Dai, Yuan; Hu, Yong; Ma, Yun-Tong; Xu, Shi-Jun; Wang, Yong-Yan

    2013-09-01

    To study the effect of Tongluo Xingnao effervescent tablet on learning and memory of dementia rats induced by injection of Abeta25-35 in hippocampus and expression of insulin-degrading enzyme in hippocampus, in order to provide basis for preventing and treating senile dementia. The dementia rat model was established by injecting Abeta25-35 in hippocampus. The rats were divided into the model control group, the Aricept (1.4 mg x kg(-1)) group, and Tongluo Xingnao effervescent tablet high dose (7.56 g x kg(-1)), middle dose (3.78 g x kg(-1)) and low dose (1.59 g x kg(-1)) groups. A sham operation group was established by injecting normal saline in hippocampus. The rats were orally given drugs for 90 days, once a day. Their learning and memory were tested by using Morris water maze. Immunohistochemistry and image analysis were utilized for a quantitative analysis on the expression of insulin-degrading enzyme in hippocampus. Tongluo Xingnao effervescent tablet could significantly shorten the escape latency of rats in the directional navigation test, prolong the retention time in the first quadrant dwell, decrease the retention time in the third quadrant dwell, increase the frequency of crossing the platform, show a more notable statistical significance than the model control group (P hippocampus, promote the expression of insulin-degrading enzyme in hippocampus, and show a more notable statistical significance than the model control group (P learning and memory capacity of AD rats and promoting the expression of insulin-degrading enzyme in hippocampus. Its effect in promoting intelligence will be related to increased insulin-degrading enzyme in hippocampus.

  16. S-Allylcysteine prevents amyloid-beta peptide-induced oxidative stress in rat hippocampus and ameliorates learning deficits.

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    Pérez-Severiano, Francisca; Salvatierra-Sánchez, Raquel; Rodríguez-Pérez, Mayra; Cuevas-Martínez, Elvis Y; Guevara, Jorge; Limón, Daniel; Maldonado, Perla D; Medina-Campos, Omar N; Pedraza-Chaverrí, José; Santamaría, Abel

    2004-04-12

    The effects of S-allylcysteine on oxidative damage and spatial learning and memory deficits produced by an intrahippocampal injection of amyloid-beta peptide 25-35 (Abeta(25-35)) in rats were investigated. The formation of reactive oxygen species, lipid peroxidation and the activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were all measured in hippocampus 120 min after Abeta(25-35) injection (1 microl of 100 microM solution), while learning and memory skills were evaluated 2 and 35 days after the infusion of Abeta(25-35) to rats, respectively. Abeta(25-35) increased both reactive oxygen species and lipid peroxidation, whereas pretreatment with S-allylcysteine (300 mg/kg, i.p.) 30 min before peptide injection decreased both of these markers. In addition, Abeta(25-35)-induced incorrect learning responses were prevented in most of trials by S-allylcysteine. In contrast, enzyme activities were found unchanged in all groups tested. Findings of this work: (i) support the participation of reactive oxygen species in Abeta(25-35)-induced hippocampal toxicity and learning deficits; and (ii) suggest that the protective effects of S-allylcysteine were related to its ability to scavenge reactive oxygen species.

  17. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus

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    Zhang, Wangxin; Zhang, Quiling; Deng, Wen; Li, Yalu; Xing, Guoqing; Shi, Xinjun; Du, Yifeng

    2014-01-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions. PMID:25317156

  18. Effects of the hippocampus on the motor expression of augmented breaths.

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    Itopa E Ajayi

    Full Text Available Augmented breaths, also known as sighs, constitute the normal repertoire of breathing in freely behaving humans and animals. The breaths are believed to be generated by neurones in the preBötzinger complex but under modulatory influence from higher brain centres, particularly in the limbic system due to the strong correlations between the expression of emotional behaviours such as anxiety and the occurrence of augmented breaths. The current study examines the role of the hippocampus in the motor expression of augmented breaths, and also examines the characteristics of eupneic breaths surrounding a sigh before and after stimulating the hippocampus in urethane anaesthetised Sprague-Dawley rats. Neurochemical microstimulation using the excitatory amino acid, D,L-Homocysteic acid, was used to locate areas in the hippocampus with the potential to modulated the motor expression of augmented breaths. The CA1 neurone cluster of the ventral hippocampus was found to completely suppress the expression of augmented breaths without affecting the intrinsic properties of the breaths. A similar neurone cluster, but in the dorsal field of the hippocampus, was also investigated and found to have no effects over the expression of augmented breaths. The data supports the hypothesis that there is a structural or functional relationship between neurones of the ventral hippocampus and brainstem nuclei that control augmented breaths. The implications of these findings in the context of behaviours are discussed but with due consideration of experimental conditions.

  19. Effects of a 4 month enriched environment on the hippocampus and the myelinated fibers in the hippocampus of middle-aged rats.

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    Qiu, Xuan; Huang, Chun-Xia; Lu, Wei; Yang, Shu; Li, Chen; Shi, Xiao-Yan; Chen, Lin; Xiu, Yun; Yang, Jun-Qing; Tang, Yong

    2012-07-17

    An enriched environment has been shown to enhance learning and memory and to induce morphological changes in the hippocampus. In the present study, 14-month (middle-aged) female and male Sprague-Dawley rats were randomly divided into enriched environment (EE) rats and standard environment (SE) rats. EE rats were reared in an enriched environment and SE rats were reared in a standard environment for 4 months. The spatial learning capacity was assessed with Morris water maze. The hippocampus and the myelinated fibers in the rat hippocampus were quantitatively investigated with a transmission electronic microscope technique and stereological methods. The female rats housed in an enriched environment showed improved performance in the Morris water maze. There was no significant difference in the total volume of hippocampus between SE rats and EE rats. The total length and total volume of the myelinated fibers in the hippocampus of the female and male EE rats were significantly increased, respectively, when compared to the female and male SE rats. The increase of the total length of the myelinated nerve fibers in the hippocampus was mainly due to the increase of the myelinated fibers with diameters from 0.5 to 0.9 μm. Our results showed that a 4 month enriched environment had significant effects on the spatial learning capacity and the myelinated fibers in the hippocampus of middle-aged rats. The present study might provide an important theoretical basis for searching for an ethological strategy to delay the progress of brain aging in the future. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Effect of pregabalin on apoptotic regulatory genes in hippocampus of rats with chronic temporal lobe epilepsy

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    ZHANG Yi-dan

    2012-04-01

    Full Text Available Objective To observe the effect of pregabalin on the expression of Bcl-2 and Bax in hippocampus of chronic epileptic rats induced by pilocarpine, to explore the anti-epileptic pharmacology mechanism of pregabalin, and its anti-apoptotic effect on hippocampal neurons of rats. Methods The model of chronic temporal lobe epileptic rats induced by lithium-pilocarpine was established, then the rats in pregabalin treatment group received intraperitoneal injection of pregabalin (40 mg/kg once daily for three weeks. The expression of Bcl-2 and Bax in hippocampus of all rats was detected by immunohistochemical technique and Western blotting. Results Compared with normal saline group rats, the expression of Bcl-2 and Bax in hippocampus of rats with chronic temporal lobe epilepsy was significantly increased (P = 0.000, for all. Pregabalin can down-regulate the expression of Bax and up-regulate the expression of Bcl-2 in hippocampus of rats compared to model group rats (P = 0.000, for all. Conclusion Pregabalin may have the effects of inhibiting cell apoptosis and protecting neurons through lowing Bax level and increasing Bcl-2 level in hippocampus of chronic temporal lobe epileptic rats.

  1. In Vitro Antioxidant Activity and In Vivo Anti-Fatigue Effect of Sea Horse (Hippocampus Peptides

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    Zebin Guo

    2017-03-01

    Full Text Available This study investigated changes the in vitro antioxidant activity of Hippocampus polypeptides during enzymatic hydrolysis, including the effects of enzyme species, enzyme concentration, material–liquid ratio, hydrolysis time, pH, and temperature of the reaction system. Its in vivo anti-fatigue activity was also studied. Hippocampus peptide prepared by papain digestion exhibited the highest 1,1-diphenyl-2-picryl-hydrazyl free radical scavenging rate (71.89% ± 1.50% and strong hydroxyl radical scavenging rate (75.53% ± 0.98%, compared to those prepared by five other commonly used enzymes (i.e., trypsin, neutral protease, compound protease, flavorzyme, and alkaline protease. Additionally, maximum antioxidant activity of Hippocampus polypeptide prepared by papain digestion was reached after hydrolysis for 40 min at pH 6.0 and 60 °C of the reaction system by using 2000 U/g enzyme and a material–liquid ratio of 1:15. Moreover, compared with the control group, Hippocampus peptide prolonged the swimming time by 33%–40%, stabilized the blood glucose concentration, increased liver glycogen levels, and decreased blood lactate levels and blood urea nitrogen levels in mice (p < 0.01. In conclusion, these results indicated that Hippocampus polypeptide prepared by papain digestion under optimal conditions exhibited high degrees of antioxidant and anti-fatigue activity.

  2. Effects of infrasound on hippocampus-dependent learning and memory in rats and some underlying mechanisms.

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    Yuan, Hua; Long, Hua; Liu, Jing; Qu, Lili; Chen, Jingzao; Mou, Xiang

    2009-09-01

    To investigate the effect of infrasound on the hippocampus-dependent spatial learning and memory as well as its underlying mechanisms, we measured the changes of cognitive abilities, brain-derived neurotrophic factor (BDNF)-tyrosine kinase receptor B (TrkB) signal transduction pathway and neurogenesis in the hippocampus of rats. The results showed that rats exposed to infrasound of 16 Hz at 130 dB for 14 days exhibited longer escape latency from day 2 and shortened time staying in the quadrant P in Morris water maze (MWM). It was found that mRNA and protein expression levels of hippocampal BDNF and TrkB were significantly decreased in real-time PCR and Western blot, and the number of BrdU-labeled cells in hippocampus was also reduced when compared to control. These results provided novel evidences that the infrasound of a certain exposure parameter can impair hippocampus-dependent learning and memory, in which the downregulation of the neuronal plasticity-related BDNF-TrkB signal pathway and less neurogenesis in hippocampus might be involved.

  3. Ginsenoside Rg1 prevents cognitive impairment and hippocampus senescence in a rat model of D-galactose-induced aging.

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    Jiahong Zhu

    Full Text Available Neurogenesis continues throughout the lifetime in the hippocampus, while the rate declines with brain aging. It has been hypothesized that reduced neurogenesis may contribute to age-related cognitive impairment. Ginsenoside Rg1 is an active ingredient of Panax ginseng in traditional Chinese medicine, which exerts anti-oxidative and anti-aging effects. This study explores the neuroprotective effect of ginsenoside Rg1 on the hippocampus of the D-gal (D-galactose induced aging rat model. Sub-acute aging was induced in male SD rats by subcutaneous injection of D-gal (120 mg/kg·d for 42 days, and the rats were treated with ginsenoside Rg1 (20 mg/kg·d, intraperitoneally or normal saline for 28 days after 14 days of D-gal injection. In another group, normal male SD rats were treated with ginsenoside Rg1 alone (20 mg/kg·d, intraperitoneally for 28 days. It showed that administration of ginsenoside Rg1 significantly attenuated all the D-gal-induced changes in the hippocampus, including cognitive capacity, senescence-related markers and hippocampal neurogenesis, compared with the D-gal-treated rats. Further investigation showed that ginsenoside Rg1 protected NSCs/NPCs (neural stem cells/progenitor cells shown by increased level of SOX-2 expression; reduced astrocytes activation shown by decrease level of Aeg-1 expression; increased the hippocampal cell proliferation; enhanced the activity of the antioxidant enzymes GSH-Px (glutathione peroxidase and SOD (Superoxide Dismutase; decreased the levels of IL-1β, IL-6 and TNF-α, which are the proinflammatory cytokines; increased the telomere lengths and telomerase activity; and down-regulated the mRNA expression of cellular senescence associated genes p53, p21Cip1/Waf1 and p19Arf in the hippocampus of aged rats. Our data provides evidence that ginsenoside Rg1 can improve cognitive ability, protect NSCs/NPCs and promote neurogenesis by enhancing the antioxidant and anti-inflammatory capacity in the

  4. Ginsenoside Rg1 prevents cognitive impairment and hippocampus senescence in a rat model of D-galactose-induced aging.

    Science.gov (United States)

    Zhu, Jiahong; Mu, Xinyi; Zeng, Jin; Xu, Chunyan; Liu, Jun; Zhang, Mengsi; Li, Chengpeng; Chen, Jie; Li, Tinyu; Wang, Yaping

    2014-01-01

    Neurogenesis continues throughout the lifetime in the hippocampus, while the rate declines with brain aging. It has been hypothesized that reduced neurogenesis may contribute to age-related cognitive impairment. Ginsenoside Rg1 is an active ingredient of Panax ginseng in traditional Chinese medicine, which exerts anti-oxidative and anti-aging effects. This study explores the neuroprotective effect of ginsenoside Rg1 on the hippocampus of the D-gal (D-galactose) induced aging rat model. Sub-acute aging was induced in male SD rats by subcutaneous injection of D-gal (120 mg/kg·d) for 42 days, and the rats were treated with ginsenoside Rg1 (20 mg/kg·d, intraperitoneally) or normal saline for 28 days after 14 days of D-gal injection. In another group, normal male SD rats were treated with ginsenoside Rg1 alone (20 mg/kg·d, intraperitoneally) for 28 days. It showed that administration of ginsenoside Rg1 significantly attenuated all the D-gal-induced changes in the hippocampus, including cognitive capacity, senescence-related markers and hippocampal neurogenesis, compared with the D-gal-treated rats. Further investigation showed that ginsenoside Rg1 protected NSCs/NPCs (neural stem cells/progenitor cells) shown by increased level of SOX-2 expression; reduced astrocytes activation shown by decrease level of Aeg-1 expression; increased the hippocampal cell proliferation; enhanced the activity of the antioxidant enzymes GSH-Px (glutathione peroxidase) and SOD (Superoxide Dismutase); decreased the levels of IL-1β, IL-6 and TNF-α, which are the proinflammatory cytokines; increased the telomere lengths and telomerase activity; and down-regulated the mRNA expression of cellular senescence associated genes p53, p21Cip1/Waf1 and p19Arf in the hippocampus of aged rats. Our data provides evidence that ginsenoside Rg1 can improve cognitive ability, protect NSCs/NPCs and promote neurogenesis by enhancing the antioxidant and anti-inflammatory capacity in the hippocampus.

  5. Effect of 17β estradiol on hippocampus region of aging female rat brain: Ultrastructural study

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    Rashmi Jha

    2015-01-01

    Full Text Available Estradiol has direct membrane-mediated effects on neurons and its effects are both neuroprotective and neurotrophic. This hormone modulates brain development and aging and affects neurochemical systems which are affected in age-related cognitive decline, AD and other neuropsychiatric disorders. The aim of the present study was to determine the effect of 17β estradiol (E2 in hippocampus region of different age groups of rats. The changes in the hippocampus region of female rat brain of different age groups with and without E2 treatment were observed by transmission electron microscopy. Age dependent changes in myelin sheath, axon and cytoplasm membrane were observed with aging in control group rat brain but the E2 treated rats showed significantly stable myelin sheath, myelin axon and cytoplasm structure. Our results showed that E2 treatment significantly effects hippocampus brain region of aging rats. These analyses revealed that fundamental age-related changes in brain and estrogen have important implications when estrogen levels and hippocampus dependent functions decline.

  6. Preventive brain radio-chemotherapy alters plasticity associated metabolite profile in the hippocampus but seems to not affect spatial memory in young leukemia patients.

    Science.gov (United States)

    Brandt, Moritz D; Brandt, Kalina; Werner, Annett; Schönfeld, Robby; Loewenbrück, Kai; Donix, Markus; Schaich, Markus; Bornhäuser, Martin; von Kummer, Rüdiger; Leplow, Bernd; Storch, Alexander

    2015-09-01

    Neuronal plasticity leading to evolving reorganization of the neuronal network during entire lifespan plays an important role for brain function especially memory performance. Adult neurogenesis occurring in the dentate gyrus of the hippocampus represents the maximal way of network reorganization. Brain radio-chemotherapy strongly inhibits adult hippocampal neurogenesis in mice leading to impaired spatial memory. To elucidate the effects of CNS radio-chemotherapy on hippocampal plasticity and function in humans, we performed a longitudinal pilot study using 3T proton magnetic resonance spectroscopy ((1)H-MRS) and virtual water-maze-tests in 10 de-novo patients with acute lymphoblastic leukemia undergoing preventive whole brain radio-chemotherapy. Patients were examined before, during and after treatment. CNS radio-chemotherapy did neither affect recall performance in probe trails nor flexible (reversal) relearning of a new target position over a time frame of 10 weeks measured by longitudinal virtual water-maze-testing, but provoked hippocampus-specific decrease in choline as a metabolite associated with cellular plasticity in (1)H-MRS. Albeit this pilot study needs to be followed up to definitely resolve the question about the functional role of adult human neurogenesis, the presented data suggest that (1)H-MRS allows the detection of neurogenesis-associated plasticity in the human brain.

  7. [The Chinese medicine nutrient diet intervention prevent against the neurologic damage induce by EMF irradiation in rat hippocampus].

    Science.gov (United States)

    Gong, Qian-Fen; Yang, Xue-Sen; Tu, Ling; Zhang, Guang-Bin; Yu, Zheng-Ping

    2013-07-01

    To observe the neurologic damage in rat hippocampus after electromagnetic field (EMF) acute or chronic irradiation and research the protective effects of Chinese medicine diet (CMD) which comprised ferulic acid, ginsenoside, astragalus polysaccharide and rhodiola sachalinensis. Eighty rats were divided into ten groups (n = 8): normal diet with shame irradiation group (NS), normal diet with chronic irradiation group (NCI), three groups of normal diet with acute irradiation after 3 h, 24 h, 72 h (NAI), Chinese medicine diet with shame irradiation group (CS), Chinese medicine diet with chronic irradiation group (CCI), three groups of Chinese medicine diet with acute irradiation after 3 h, 24 h, 72 h (CAI). The chronic EMF irradiation were performed by electromagnetic wave at 15 W/cm2 for 20 min everyday for 8 weeks continuously. The acute EMF irradiation were performed by electromagnetic wave at 65 W/cm2 for 20 min after feeding with CMD for 8 weeks. The learning and memory were evaluated by Morris water maze before/after electromagnetic wave irradiation. The apoptotic cells in hippocampus was detected by Tunel staining. The peroxidation damage of EMF and the protective effect of CMD intervention were assayed by measuring superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and reactive oxygen species (ROS). The acute and chronic EMF irradiation disturbed the ability of learning and memory significantly (P EMF irradiation (P EMF irradiation induced the oxidative stress by down-regulating SOD activity, GSH-Px activity, ROS inhibiting and up-regulating the content of MDA obviously (P EMF irradiation could initiate neurologic damage in hippocampus. CMD intervention has protective effect on the impaired learning and memory, the neuron apoptosis, the peroxidation damage induced by EMF irradiation. CMD intervention plays a significant protective role in antagonizing neurologic damage in the later stage of acute irradiation and chronic

  8. Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

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    P S Santos

    2011-01-01

    Full Text Available Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p. with 0.9% saline (Control, pilocarpine (400 mg/kg, Pilocarpine, LA (10 mg/kg, LA, and the association of LA (10 mg/kg plus pilocarpine (400 mg/kg, that was injected 30 min before of administration of LA (LA plus pilocarpine. Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC. In pilocarpine group, it was observed a significant increase in glutamate content (37% and a decrease in taurine level (18% in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28% and augmented taurine content (32% in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.

  9. The effects of study task on prestimulus subsequent memory effects in the hippocampus.

    Science.gov (United States)

    de Chastelaine, Marianne; Rugg, Michael D

    2015-11-01

    Functional magnetic resonance imaging (fMRI) was employed to examine the effects of a study task manipulation on pre-stimulus activity in the hippocampus predictive of later successful recollection. Eighteen young participants were scanned while making either animacy or syllable judgments on visually presented study words. Cues presented before each word denoted which judgment should be made. Following the study phase, a surprise recognition memory test was administered in which each test item had to be endorsed as "Remembered," "Known," or "New." As expected, "deep" animacy judgments led to better memory for study items than did "shallow" syllable judgments. In both study tasks, pre-stimulus subsequent recollection effects were evident in the interval between the cue and the study item in bilateral anterior hippocampus. However, the direction of the effects differed according to the study task: whereas pre-stimulus hippocampal activity on animacy trials was greater for later recollected items than items judged old on the basis of familiarity (replicating prior findings), these effects reversed for syllable trials. We propose that the direction of pre-stimulus hippocampal subsequent memory effects depends on whether an optimal pre-stimulus task set facilitates study processing that is conducive or unconducive to the formation of contextually rich episodic memories. © 2015 Wiley Periodicals, Inc.

  10. Effects of a toxin isolated from Tityus bahiensis scorpion venom on the hippocampus of rats.

    Science.gov (United States)

    Ossanai, Luciene Toshietakeishi; Lourenço, Geane Antiques; Nencioni, Ana Leonor A; Lebrun, Ivo; Yamanouye, Norma; Dorce, Valquiria Abrão Coronado

    2012-09-17

    The objective of the present study was to determine the effects of a toxin from T. bahiensis scorpion venom on the hippocampus of rats. This toxin, called Tb V-4, was chosen since it shows remarkable convulsive activity. Male Wistar rats weighing 250g were used. The toxin (1.0μg/μl) was injected into the hippocampus. The animals were then submitted to electroencephalographic and behavioral examinations or to microdialysis to determine the levels of neurotransmitters. The location of the implanted guide cannulae and electrodes was checked histologically. The number of cells in the CA1, CA3 and CA4 areas of the hippocampus was determined by light microscopy. Changes in the concentration of cytosolic free calcium were evaluated by confocal microscopy. The toxin evoked behavioral alterations such as wet dog shakes, myoclonus, yawning and orofacial automatisms. Electroencephalographic recordings exhibited alterations such as isolated or grouped spikes and epileptic-like discharges. Injection of the toxin augmented glutamate concentration in the extracellular fluid in some animals. There was also a decrease in the number of pyramidal cells, mainly in the CA1 and CA4 areas for some rats. In some slices of the hippocampus, an increase in intracellular calcium mobilization was seen. The present results suggest that the Tb V-4 toxin may be responsible for the epileptic and behavioral effects observed with the crude venom. We suggest that the convulsive and degenerative effects induced by the toxin could be due to the enhanced release of excitatory amino acids involved in the most important pathways of the hippocampus. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. In Vitro Antioxidant Activity and In Vivo Anti-Fatigue Effect of Sea Horse (Hippocampus) Peptides.

    Science.gov (United States)

    Guo, Zebin; Lin, Duanquan; Guo, Juanjuan; Zhang, Yi; Zheng, Baodong

    2017-03-18

    This study investigated changes the in vitro antioxidant activity of Hippocampus polypeptides during enzymatic hydrolysis, including the effects of enzyme species, enzyme concentration, material-liquid ratio, hydrolysis time, pH, and temperature of the reaction system. Its in vivo anti-fatigue activity was also studied. Hippocampus peptide prepared by papain digestion exhibited the highest 1,1-diphenyl-2-picryl-hydrazyl free radical scavenging rate (71.89% ± 1.50%) and strong hydroxyl radical scavenging rate (75.53% ± 0.98%), compared to those prepared by five other commonly used enzymes (i.e., trypsin, neutral protease, compound protease, flavorzyme, and alkaline protease). Additionally, maximum antioxidant activity of Hippocampus polypeptide prepared by papain digestion was reached after hydrolysis for 40 min at pH 6.0 and 60 °C of the reaction system by using 2000 U/g enzyme and a material-liquid ratio of 1:15. Moreover, compared with the control group, Hippocampus peptide prolonged the swimming time by 33%-40%, stabilized the blood glucose concentration, increased liver glycogen levels, and decreased blood lactate levels and blood urea nitrogen levels in mice (p antioxidant and anti-fatigue activity.

  12. Neuroprotective Effect of Ginseng against Alteration of Calcium Binding Proteins Immunoreactivity in the Mice Hippocampus after Radiofrequency Exposure

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    Dhiraj Maskey

    2013-01-01

    Full Text Available Calcium binding proteins (CaBPs such as calbindin D28-k, parvalbumin, and calretinin are able to bind Ca2+ with high affinity. Changes in Ca2+ concentrations via CaBPs can disturb Ca2+ homeostasis. Brain damage can be induced by the prolonged electromagnetic field (EMF exposure with loss of interacellular Ca2+ balance. The present study investigated the radioprotective effect of ginseng in regard to CaBPs immunoreactivity (IR in the hippocampus through immunohistochemistry after one-month exposure at 1.6 SAR value by comparing sham control with exposed and ginseng-treated exposed groups separately. Loss of dendritic arborization was noted with the CaBPs in the Cornu Ammonis areas as well as a decrease of staining intensity of the granule cells in the dentate gyrus after exposure while no loss was observed in the ginseng-treated group. A significant difference in the relative mean density was noted between control and exposed groups but was nonsignificant in the ginseng-treated group. Decrease in CaBP IR with changes in the neuronal staining as observed in the exposed group would affect the hippocampal trisynaptic circuit by alteration of the Ca2+ concentration which could be prevented by ginseng. Hence, ginseng could contribute as a radioprotective agent against EMF exposure, contributing to the maintenance of Ca2+ homeostasis by preventing impairment of intracellular Ca2+ levels in the hippocampus.

  13. Effects of Asiatic Acid on Spatial Working Memory and Cell Proliferation in the Adult Rat Hippocampus

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    Apiwat Sirichoat

    2015-10-01

    Full Text Available Asiatic acid is a pentacyclic triterpene from Centella asiatica. Previous studies have reported that asiatic acid exhibits antioxidant and neuroprotective activities in cell culture. It also prevents memory deficits in animal models. The objective of this study was to investigate the relationship between spatial working memory and changes in cell proliferation within the hippocampus after administration of asiatic acid to male Spraque-Dawley rats. Control rats received vehicle (propylene glycol while treated rats received asiatic acid (30 mg/kg orally for 14 or 28 days. Spatial memory was determined using the novel object location (NOL test. In animals administered asiatic acid for both 14 and 28 days, the number of Ki-67 positive cells in the subgranular zone of the dentate gyrus was significantly higher than in control animals. This was associated with a significant increase in their ability to discriminate between novel and familiar object locations in a novel object discrimination task, a hippocampus-dependent spatial memory test. Administration of asiatic acid also significantly increased doublecortin (DCX and Notch1 protein levels in the hippocampus. These findings demonstrate that asiatic acid treatment may be a potent cognitive enhancer which improves hippocampal-dependent spatial memory, likely by increasing hippocampal neurogenesis.

  14. Differential effects of nicotine against stress-induced changes in dopaminergic system in rat striatum and hippocampus.

    Science.gov (United States)

    Pawlak, R; Takada, Y; Takahashi, H; Urano, T; Ihara, H; Nagai, N; Takada, A

    2000-01-10

    A number of studies have shown an increase in nicotine self-administration among smokers when exposed to stress. Since it is well known that nicotine or stress alter the dopaminergic system, we examined the effect of chronic nicotine administration on the dopamine level and its metabolism in the striatum and the hippocampus during stressful conditions in rats. Nicotine (0.4 mg/kg, i.p. for 14 days) increased the dopamine level in the striatum (Pstress sharply elevated the dopamine level (PNicotine pretreatment attenuated some of these changes in a region- and time-dependent manner. However, stress induced a decrease in dopamine turnover in the hippocampus (Pnicotine failed to prevent this effect. Stress-induced alterations gradually returned toward normal during the 48-h observation period, and in some cases this was facilitated by nicotine. Thus, we demonstrated differential, region- and time-dependent protective effects of chronic nicotine administration against stress-induced changes in dopamine levels and release in brain regions critically affected by stress.

  15. The effects of concomitant Ginkgo intake on noise induced Hippocampus injury. Possible auditory clinical correlate

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    Alaa Abousetta

    2014-11-01

    Full Text Available This study was conducted to determine the injurious effects of noise on the hippocampus, and to show whether Ginkgo biloba (Gb has any modulatory effect on hippocampal injury. Fifteen adult male albino rats were divided into three groups; control group, noise group and protected group. The noise group was exposed to 100 dB Sound pressure level (SPL white noise, six hours/day for four consecutive weeks. The protected group was exposed to the same noise level with the administration of Gb extract to the animals (50 mg/kg daily for 4 weeks. In the noise exposed group, both pyramidal cell layer and dentate gyrus (DG granular cell layer showed a decrease in thickness with loss and degeneration of many cells. The protected group showed preservation of many parameters as compared to the noise group i.e. increase in thickness of Cornu Ammonis area3 (CA3 & DG; increase in surface area of cells and increased vascularity. In conclusion, noise had detrimental effects on cells of Cornu Ammonis area1 (CA1, CA3 & DG of the hippocampus. In view of this finding, the clinical auditory hazardous effects in people exposed to harmful noise such as tinnitus, as well as memory disturbances and learning disabilities might have a new dimension. The administration of Gb protected the hippocampus against the injurious effect of noise. The probable mechanism and usefulness of Gb in reducing the previously mentioned effects are discussed.

  16. The Effects of Hypergravic Fields on Neural Signalling in the Hippocampus

    Science.gov (United States)

    Horowitz, John; Horwitz, Barbara

    1991-01-01

    The goal of this grant is to study the effect of hypergravic fields on the modulation of hippocampal electrical activity by serotonin (5-HT). The proposed study represents a shift from our previous NASA grants covering three diverse areas in neurobiology (thermoregulation, vestibular and auditory brainstem evoked responses, and the hippocampus) to consideration of only one of these areas, the hippocampus. To place our proposed hippocampal experiments in context with relevant Spacelab-3 experiments and hypergravic experiments, two experiments on receptor changes in animals exposed to altered gravitational fields are first described. Our experiments build on these structural/biochemical observations and extend investigations to related electrical activity at 1 G and in hypergravic fields. The background continues with a review of past studies at 1G related to effects of serotonin on hippocampal electrical activity (i.e., population spikes, intracellular potentials).

  17. Effects of sleep deprivation on extracellular serotonin in hippocampus and frontal cortex of the rat

    OpenAIRE

    Bjorvatn, B; Grønli, J; Hamre, F; Sørensen, E; Fiske, E; Bjorkum, Alvhild Alette; Portas, CM; Ursin, R.

    2002-01-01

    Sleep deprivation improves the mood of depressed patients, but the exact mechanism behind this effect is unclear. An enhancement of serotonergic neurotransmission has been suggested. In this study, we used in vivo microdialysis to monitor extracellular serotonin in the hippocampus and the frontal cortex of rats during an 8 h sleep deprivation period. These brain regions were selected since both have been implicated in depression. The behavioral state of the animal was continuously monitored b...

  18. Early Life Stress Effects on Glucocorticoid-BDNF Interplay in the Hippocampus.

    Science.gov (United States)

    Daskalakis, Nikolaos P; De Kloet, Edo Ronald; Yehuda, Rachel; Malaspina, Dolores; Kranz, Thorsten M

    2015-01-01

    Early life stress (ELS) is implicated in the etiology of multiple psychiatric disorders. Important biological effects of ELS are manifested in stress-susceptible regions of the hippocampus and are partially mediated by long-term effects on glucocorticoid (GC) and/or neurotrophin signaling pathways. GC-signaling mediates the regulation of stress response to maintain homeostasis, while neurotrophin signaling plays a key role in neuronal outgrowth and is crucial for axonal guidance and synaptic integrity. The neurotrophin and GC-signaling pathways co-exist throughout the central nervous system (CNS), particularly in the hippocampus, which has high expression levels of glucocorticoid-receptors (GR) and mineralocorticoid-receptors (MR) as well as brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB). This review addresses the effects of ELS paradigms on GC- and BDNF-dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of common stress-related disorders.

  19. Early Life Stress Effects on the Glucocorticoid - BDNF interplay in the Hippocampus

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    Nikolaos P Daskalakis

    2015-11-01

    Full Text Available Early life stress (ELS is implicated in the etiology of multiple psychiatric disorders. Important biological effects of ELS are manifested in stress-susceptible regions of the hippocampus and are partially mediated by long-term effects on glucocorticoid and/or neurotrophin signaling pathways. Glucocorticoid (GC signaling mediates the regulation of the stress response to maintain homeostasis, while neurotrophin signaling plays a key role in neuronal outgrowth and is crucial for axonal guidance and synaptic integrity. The neurotrophin and glucocorticoid signaling pathways co-exist throughout the central nervous system (CNS, particularly in the hippocampus, which has high expression of glucocorticoid and mineralocorticoid receptors (GR and MR as well as brain-derived neurotrophic factor (BDNF and its receptor, tropomyosin-related kinase receptor B (TrkB. This review addresses the effects of ELS paradigms on GC- and BDNF- dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of common stress-related disorders.

  20. Lasting Differential Effects on Plasticity Induced by Prenatal Stress in Dorsal and Ventral Hippocampus

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    Gayane Grigoryan

    2016-01-01

    Full Text Available Early life adversaries have a profound impact on the developing brain structure and functions that persist long after the original traumatic experience has vanished. One of the extensively studied brain structures in relation to early life stress has been the hippocampus because of its unique association with cognitive processes of the brain. While the entire hippocampus shares the same intrinsic organization, it assumes different functions in its dorsal and ventral sectors (DH and VH, resp., based on different connectivity with other brain structures. In the present review, we summarize the differences between DH and VH and discuss functional and structural effects of prenatal stress in the two sectors, with the realization that much is yet to be explored in understanding the opposite reactivity of the DH and VH to stressful stimulation.

  1. Effect of phenylsuccinate on potassium- and ischemia-induced release of glutamate in rat hippocampus monitored by microdialysis

    DEFF Research Database (Denmark)

    Christensen, Thomas; Bruhn, T; Diemer, Nils Henrik

    1991-01-01

    The extracellular concentration of glutamate in rat hippocampus during physiological conditions, elevated extracellular K+ and global ischemia was followed by microdialysis and subsequent determination of glutamate by HPLC. The effect of phenylsuccinate, an inhibitor of the mitochondrial dicarbox...

  2. Lithium chloride administration prevents spatial learning and memory impairment in repeated cerebral ischemia-reperfusion mice by depressing apoptosis and increasing BDNF expression in hippocampus.

    Science.gov (United States)

    Fan, Mingyue; Jin, Wei; Zhao, Haifeng; Xiao, Yining; Jia, Yanqiu; Yin, Yu; Jiang, Xin; Xu, Jing; Meng, Nan; Lv, Peiyuan

    2015-09-15

    Lithium has been reported to have neuroprotective effects, but the preventive and treated role on cognition impairment and the underlying mechanisms have not been determined. In the present study, C57Bl/6 mice were subjected to repeated bilateral common carotid artery occlusion to induce the learning and memory deficits. 2 mmol/kg or 5 mmol/kg of lithium chloride (LiCl) was injected intraperitoneally per day before (for 7 days) or post (for 28 days) the operation. This repeated cerebral ischemia-reperfusion (IR) induced dynamic overexpression of ratio of Bcl-2/Bax and BDNF in hippocampus of mice. LiCl pretreatment and treatment significantly decreased the escape latency and increased the percentage of time that the mice spent in the target quadrant in Morris water maze. 2 mmol/kg LiCl evidently reversed the morphologic changes, up-regulated the survival neuron count and increased the BDNF gene and protein expression. 5 mmol/kg pre-LiCl significantly increased IR-stimulated reduce of Bcl-2/Bax and p-CREB/CREB. These results described suggest that pre-Li and Li treatment may induce a pronounced prevention on cognitive impairment. These effects may relay on the inhibition of apoptosis and increasing BDNF and p-CREB expression. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. The effects of neonatal amygdala or hippocampus lesions on adult social behavior.

    Science.gov (United States)

    Bliss-Moreau, Eliza; Moadab, Gilda; Santistevan, Anthony; Amaral, David G

    2017-03-30

    The present report details the final phase of a longitudinal evaluation of the social behavior in a cohort of adult rhesus monkeys that received bilateral neurotoxic lesions of the amygdala or hippocampus, or sham operations at 2 weeks of age. Results were compared to previous studies in which adult animals received amygdala lesions and were tested in a similar fashion. Social testing with four novel interaction partners occurred when the animals were between 7 and 8 years of age. Experimental animals interacted with two male and two female partners in two conditions - one in which physical access was restricted (the constrained social access condition) and a second in which physical access was unrestricted (the unconstrained social access condition). Across conditions and interaction partners, there were no significant effects of lesion condition on the frequency or duration of social interactions. As a group, the hippocampus-lesioned animals generated the greatest number of communicative signals during the constrained social access condition. Amygdala-lesioned animals generated more frequent stress-related behaviors and were less exploratory. Amygdala and hippocampus-lesioned animals demonstrated greater numbers of stereotypies than control animals. Subtle, lesion-based differences in the sequencing of behaviors were observed. These findings suggest that alterations of adult social behavior are much less prominent when damage to the amygdala occurs early in life rather than in adulthood. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Effect of Protein Malnutrition on Efferent Projections of Amygdala to the Hippocampus

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    Gholamreza Hassanzadeh

    2010-11-01

    Full Text Available ABSTRACTIntroduction: Previous investigations have shown that protein malnutrition can alters the structure and function of some areas of hippocampal formation. We investigated the effect of protein malnutrition on amygdaloid projections to the CA1 hippocampal area. In this study we investigated level and pattern of distribution of efferent projections from amygdala to hippocampus in the rat by Horseradish Peroxidas (HRP neural tract tracing in 2 groups Control group fed with regular diet (% 18 proteinsand case group fed with low protein diet (%8. We used SPSS 11.0 (T test & mann-withney Software for data analysis.Methods: Following injection of HRP to CA1 region of hippocampus in the control group Rats, Labelled neurons showed more density in the Basolateral, Cortical and Medial nuclear Groups. Having done the analysis and examining the relations between the case data and those of the control groups, we found that number of labelled neurons in the Basolateral, Cortical & medial nuclei were decreased in the case group(p<0.05. Our findings showed that different nuclei of amygdala (Basolateral, Cortical and Medial send projections to CA1 region of hippocampus Among, them basolateral nuclei group send the most projections . Discussion: This results may be caused by decrease of activity of neural cells after protein malnutrition, that can results in impairment in growth and development of nervous system. Also it is possible that axoplasmic transfer rate maybe decreased in this condition.

  5. Effect of Protein Malnutrition on Efferent Projections of Amygdala to the Hippocampus

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    Gholamreza Hassanzadeh

    2010-11-01

    Full Text Available ABSTRACTIntroduction: Previous investigations have shown that protein malnutrition can alters the structure and function of some areas of hippocampal formation. We investigated the effect of protein malnutrition on amygdaloid projections to the CA1 hippocampal area. In this study we investigated level and pattern of distribution of efferent projections from amygdala to hippocampus in the rat by Horseradish Peroxidas (HRP neural tract tracing in 2 groups; Control group fed with regular diet (% 18 proteinsand case group fed with low protein diet (%8. We used SPSS 11.0 (T test & mann-withney Software for data analysis.Methods: Following injection of HRP to CA1 region of hippocampus in the control group Rats, Labelled neurons showed more density in the Basolateral, Cortical and Medial nuclear Groups. Having done the analysis and examining the relations between the case data and those of the control groups, we found that number of labelled neurons in the Basolateral, Cortical & medial nuclei were decreased in the case group(p<0.05. Our findings showed that different nuclei of amygdala (Basolateral, Cortical and Medial send projections to CA1 region of hippocampus; Among, them basolateral nuclei group send the most projections . Discussion: This results may be caused by decrease of activity of neural cells after protein malnutrition, that can results in impairment in growth and development of nervous system. Also it is possible that axoplasmic transfer rate maybe decreased in this condition.

  6. Effect of seizure on hippocampus in mesial temporal lobe epilepsy and neocortical epilepsy: an MRS study

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S.K.; Kim, D.W.; Kim, K.K. [Seoul National University College of Medicine, Seoul National University Hospital, Department of Neurology, Chongno ku, Seoul (Korea); Chung, C.K. [Seoul National University College of Medicine, Seoul National University Hospital, Department of Neurosurgery, Chongno ku, Seoul (Korea); Song, I.C.; Chang, K.H. [Seoul National University College of Medicine, Seoul National University Hospital, Department of Radiology, Chongno ku, Seoul (Korea)

    2005-12-01

    This study was performed to evaluate the effect of seizures on the bilateral hippocampus in mesial temporal lobe epilepsy (mTLE) and neocortical epilepsy by single voxel proton magnetic resonance spectroscopy (MRS). Forty-one patients with mTLE having unilateral hippocampal sclerosis and 43 patients with a neocortical epilepsy who underwent subsequent epilepsy surgery were recruited. Ninety-five percent confidence intervals of N-acetyl aspartate/choline (NAA/Cho) and NAA/creatine (NAA/Cr) ratios in 20 healthy control subjects were used as threshold values to determine abnormal NAA/Cho and NAA/Cr. NAA/Cho and NAA/Cr were significantly lower in the ipsilateral hippocampus of mTLE and neocortical epilepsy. Using asymmetry indices for patients with bilaterally abnormal ratios of NAA/Cho and NAA/Cr in addition to using unilateral abnormal ratio, the seizure focus was correctly lateralized in 65.9% of patients with mTLE and 48.8% of neocortical epilepsy patients. Bilateral NAA/Cho abnormality was significantly related to a poor surgical outcome in mTLE. No significant relationship was found between the results of NAA/Cho or NAA/Cr and surgical outcome in neocortical epilepsy. The mean contralateral NAA/Cr ratio of the hippocampus in mTLE was significantly lower in patients with a history of secondary generalized tonic-clonic seizure (SGTCS) than in those without. (orig.)

  7. EFFECT OF EXERCISE ON LEARNING, MEMORY AND LEVELS OF EPINEPHRINE IN RATS' HIPPOCAMPUS

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    Hojjatallah Alaei

    2003-09-01

    Full Text Available The aim of the present study was to investigate effect of exercise on learning and memory, long-term potentiation and levels of epinephrine in the rat hippocampus. Treadmill trained (one hour at 17 m·min-1 for 10 days and corresponding control rats went through spatial learning process on a Morris water maze for 8 days. The time to reach the platform (latency, the length of swim path, and the swim speed were used for the evaluation of spatial learning. Our results showed that physical activity produced a significant enhancement in spatial learning, with a decreased path length (p<0.05 and latency (p<0.05 to the platform in Morris water maze, without affecting the swim speed. Furthermore, the levels of the epinephrine were significantly increased (p<0.05 in hippocampus of the exercised rats. In conclusion our findings suggest that the enhanced learning by exercise may be mediated through the activation of adrenoceptors in the hippocampus and epinephrine may play an important role in potentiation of learning

  8. Hippocampus and two-way active avoidance conditioning: Contrasting effects of cytotoxic lesion and temporary inactivation.

    Science.gov (United States)

    Wang, Jia; Bast, Tobias; Wang, Yu-Cong; Zhang, Wei-Ning

    2015-12-01

    Hippocampal lesions tend to facilitate two-way active avoidance (2WAA) conditioning, where rats learn to cross to the opposite side of a conditioning chamber to avoid a tone-signaled footshock. This classical finding has been suggested to reflect that hippocampus-dependent place/context memory inhibits 2WAA (a crossing response to the opposite side is inhibited by the memory that this is the place where a shock was received on the previous trial). However, more recent research suggests other aspects of hippocampal function that may support 2WAA learning. More specifically, the ventral hippocampus has been shown to contribute to behavioral responses to aversive stimuli and to positively modulate the meso-accumbens dopamine system, whose activation has been implicated in 2WAA learning. Permanent hippocampal lesions may not reveal these contributions because, following complete and permanent loss of hippocampal output, other brain regions may mediate these processes or because deficits could be masked by lesion-induced extra-hippocampal changes, including an upregulation of accumbal dopamine transmission. Here, we re-examined the hippocampal role in 2WAA learning in Wistar rats, using permanent NMDA-induced neurotoxic lesions and temporary functional inhibition by muscimol or tetrodotoxin (TTX) infusion. Complete hippocampal lesions tended to facilitate 2WAA learning, whereas ventral (VH) or dorsal hippocampal (DH) lesions had no effect. In contrast, VH or DH muscimol or TTX infusions impaired 2WAA learning. Ventral infusions caused an immediate impairment, whereas after dorsal infusions rats showed intact 2WAA learning for 40-50 min, before a marked deficit emerged. These data show that functional inhibition of ventral hippocampus disrupts 2WAA learning, while the delayed impairment following dorsal infusions may reflect the time required for drug diffusion to ventral hippocampus. Overall, using temporary functional inhibition, our study shows that the ventral

  9. [Effect of electromagnetic radiation on discharge activity of neurons in the hippocampus CA1 in rats].

    Science.gov (United States)

    Tong, Jun; Chen, Su; Liu, Xiang-Ming; Hao, Dong-Mei

    2013-09-01

    In order to explore effect of electromagnetic radiation on learning and memory ability of hippocampus neuron in rats, the changes in discharge patterns and overall electrical activity of hippocampus neuron after electromagnetic radiation were observed. Rat neurons discharge was recorded with glass electrode extracellular recording technology and a polygraph respectively. Radiation frequency of electromagnetic wave was 900 MHZ and the power was 10 W/m2. In glass electrode extracellular recording, the rats were separately irradiated for 10, 20, 30, 40, 50 and 60 min, every points repeated 10 times and updated interval of 1h, observing the changes in neuron discharge and spontaneous discharge patterns after electromagnetic radiation. In polygraph recording experiments, irradiation group rats for five days a week, 6 hours per day, repeatedly for 10 weeks, memory electrical changes in control group and irradiation group rats when they were feeding were repeatedly monitored by the implanted electrodes, observing the changes in peak electric digits and the largest amplitude in hippocampal CA1 area, and taking some electromagnetic radiation sampling sequence for correlation analysis. (1) Electromagnetic radiation had an inhibitory role on discharge frequency of the hippocampus CA1 region neurons. After electromagnetic radiation, discharge frequency of the hippocampus CA1 region neurons was reduced, but the changes in scale was not obvious. (2) Electromagnetic radiation might change the spontaneous discharge patterns of hippocampus CA1 region neurons, which made the explosive discharge pattern increased obviously. (3) Peak potential total number within 5 min in irradiation group was significantly reduced, the largest amplitude was less than that of control group. (4) Using mathematical method to make the correlation analysis of the electromagnetic radiation sampling sequence, that of irradiation group was less than that of control group, indicating that there was a tending

  10. Effects of preweaning environmental enrichment on hippocampus-dependent learning and memory in developing rats.

    Science.gov (United States)

    Lu, Cheng-Qiu; Zhong, Le; Yan, Chong-Huai; Tian, Ying; Shen, Xiao-Ming

    2017-02-15

    Previous studies have shown that environmental enrichment (EE) improves learning and memory in adult animals. However, the effects of preweaning EE (preEE) on hippocampus-dependent learning and memory as well as its possible mechanisms are poorly understood. Here we report that preEE enhanced the exploratory activity in rats immediately after weaning, and the EE group showed greater performance in a passive avoidance task than the control group (phippocampus-dependent learning and memory function as postweaning EE does, and the upregulated activation of the ERK signal transduction pathway may be the underlying molecular mechanism. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  11. The effects of doxepin on stress-induced learning, memory impairments, and TNF-α level in the rat hippocampus.

    Science.gov (United States)

    Azadbakht, Ali Ahmad; Radahmadi, Maryam; Javanmard, Shaghayegh Haghjooye; Reisi, Parham

    2015-01-01

    Stress has a profound impact on the nervous system and causes cognitive problems that are partly related to the inflammatory effects. Besides influencing the content of neurotransmitters, antidepressants such as doxepin are likely to have anti-inflammatory, anti-oxidative, and anti-apoptotic effects. Therefore, the present study investigated the effects of doxepin on passive avoidance learning and the levels of tumor necrosis factor-alpha (TNF-α) in the rat hippocampus following repeated restraint stress. Male Wistar rats were divided into five groups. Chronic stress was induced by keeping animals within an adjustable restraint chamber for 6 h every day for 21 successive days. In stress-doxepin group, stressed rats were given 1, 5 and 10 mg/kg of doxepin intraperitoneally (i.p) for 21 days and before placing them in restraint chamber. Healthy animals who served as control group and stressed rats received normal saline i.p. For evaluation of learning and memory, initial latency and step-through latency were determined using passive avoidance learning test. TNF-α levels were measured in hippocampus by enzyme-linked immunosorbant assay (ELISA) at the end of experiment. Induced stress considerably decreased the step through latencies in the rats (PStress-doxepin groups did not reveal any differences compared to control group at any given doses. TNF-α level was increased significantly (Pstress group. Only the low dose of doxepin (1 mg/kg) decreased TNF-α level. The present findings indicated that learning and memory are impaired in stressful conditions and doxepin prevented memory deficit. It seems that inflammation may involve in induced stress memory deficits, and that doxepin is helpful in alleviating the neural complications due to stress.

  12. Histopathologic Effect of Prenatal Topiramate Exposure on Rat Cerebral Cortex and Hippocampus

    Directory of Open Access Journals (Sweden)

    Hagar A Hashish

    2014-04-01

    Material and methods: 12 female pregnant rats were divided into control and treated groups, 6 rats in each group. The treated group was given topiramate dissolved in tap water, from day 0 of pregnancy till the delivery, through oral route in dose of 200mg/kg. The control group received tap water at the same time. In the end of the treatment, the cerebral cortex and the hippocampus were stained with hematoxylin and eosin (H and E and immnunohistochemically for glial fibrillary acidic protein (GFAP. Results: The control rat cerebral cortex showed that granule cells were small cell with dense cytoplasm, pyramidal cells appeared with triangular cell body, light cytoplasm and small nucleus. Strong GFAP positive immunostaining was detected in the astrocytes in both granule cell and pyramidal cell layers. The pyramidal cells in Cornu Ammonis showed characteristic palisade arrangement, with lightly stained cytoplasm and central nucleus. Granule cells of the dentate gyrus were rounded, packed, dense. Strong GFAP positive immunostaining was detected in the astrocytes in both pyramidal cell and granule cell layers. In treated rats, granule and pyramidal cells in the cerebral cortex and hippocampus were disorganized with signs of degeneration. Faint GFAP positive immunostaining was detected in the astrocytes in granule and pyramidal cell layers. Conclusion: Long-term daily use of topiramate during pregnancy can lead to noticeable pathological neurotoxic effect in the cerebral cortex and hippocampus which may be implicated in cognitive affection. Neurological effect of topiramate necessitates further investigations. [J Interdiscipl Histopathol 2014; 2(2.000: 61-68

  13. Caffeine consumption prevents diabetes-induced memory impairment and synaptotoxicity in the hippocampus of NONcZNO10/LTJ mice

    National Research Council Canada - National Science Library

    Duarte, João M N; Agostinho, Paula M; Carvalho, Rui A; Cunha, Rodrigo A

    2012-01-01

    ... (a mixed antagonist of adenosine A(1) and A(2A) receptors) emerges as a promising candidate since caffeine consumption reduces the risk of diabetes and effectively prevents memory deficits caused by different noxious stimuli...

  14. Altered Effective Connectivity of Hippocampus-Dependent Episodic Memory Network in mTBI Survivors

    Directory of Open Access Journals (Sweden)

    Hao Yan

    2016-01-01

    Full Text Available Traumatic brain injuries (TBIs are generally recognized to affect episodic memory. However, less is known regarding how external force altered the way functionally connected brain structures of the episodic memory system interact. To address this issue, we adopted an effective connectivity based analysis, namely, multivariate Granger causality approach, to explore causal interactions within the brain network of interest. Results presented that TBI induced increased bilateral and decreased ipsilateral effective connectivity in the episodic memory network in comparison with that of normal controls. Moreover, the left anterior superior temporal gyrus (aSTG, the concept forming hub, left hippocampus (the personal experience binding hub, and left parahippocampal gyrus (the contextual association hub were no longer network hubs in TBI survivors, who compensated for hippocampal deficits by relying more on the right hippocampus (underlying perceptual memory and the right medial frontal gyrus (MeFG in the anterior prefrontal cortex (PFC. We postulated that the overrecruitment of the right anterior PFC caused dysfunction of the strategic component of episodic memory, which caused deteriorating episodic memory in mTBI survivors. Our findings also suggested that the pattern of brain network changes in TBI survivors presented similar functional consequences to normal aging.

  15. Effect of Prolonged Simulated Microgravity on Metabolic Proteins in Rat Hippocampus: Steps toward Safe Space Travel.

    Science.gov (United States)

    Wang, Yun; Javed, Iqbal; Liu, Yahui; Lu, Song; Peng, Guang; Zhang, Yongqian; Qing, Hong; Deng, Yulin

    2016-01-04

    Mitochondria are not only the main source of energy in cells but also produce reactive oxygen species (ROS), which result in oxidative stress when in space. This oxidative stress is responsible for energy imbalances and cellular damage. In this study, a rat tail suspension model was used in individual experiments for 7 and 21 days to explore the effect of simulated microgravity (SM) on metabolic proteins in the hippocampus, a vital brain region involved in learning, memory, and navigation. A comparative (18)O-labeled quantitative proteomic strategy was used to observe the differential expression of metabolic proteins. Forty-two and sixty-seven mitochondrial metabolic proteins were differentially expressed after 21 and 7 days of SM, respectively. Mitochondrial Complex I, III, and IV, isocitrate dehydrogenase and malate dehydrogenase were down-regulated. Moreover, DJ-1 and peroxiredoxin 6, which defend against oxidative damage, were up-regulated in the hippocampus. Western blot analysis of proteins DJ-1 and COX 5A confirmed the mass spectrometry results. Despite these changes in mitochondrial protein expression, no obvious cell apoptosis was observed after 21 days of SM. The results of this study indicate that the oxidative stress induced by SM has profound effects on metabolic proteins.

  16. Pharmacological blockade of either, cannabinoid CB1 or CB2 receptors, prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rats.

    Directory of Open Access Journals (Sweden)

    EDUARDO eBLANCO-CALVO

    2014-01-01

    Full Text Available Addiction to major drugs of abuse such as cocaine has been recently linked to alterations on adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulated this proliferative response since pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors by modulating not only neurogenesis but also cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation . To this end we examined if pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg or CB2 receptors (AM630, 3 mg/kg affects cell proliferation (labeled with BrdU, found in the subventricular zone (SVZ of the lateral ventricles and the dentate subgranular zone (SGZ. In addition, we measured cell apoptosis (monitored by the expression of cleaved caspase-3 and glial activation ( by analizing the expression of GFAP and Iba-1 in the striatum and hippocampus, during acute or repeated (4 days cocaine administration (20 mg/kg. Results showed that acute cocaine decreased the number of BrdU+ cells in SVZ and SGZ. In contrast, repeated cocaine reduced the number of BrdU+ cells in SVZ only. Both acute and repeated cocaine increased the number of cleaved caspase-3+, GFAP+ and Iba1+ cells in the hippocampus, an effect counteracted by AM630 or Rimonabant that increased the number of BrdU+, GFAP+ and Iba1+ cells in the hippocampus. These results indicate that changes on neurogenic, apoptotic and gliosis processes, which were produced as a consequence of repeated cocaine administration, were normalized by the pharmacological blockade of CB1 and CB2. The restoring effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with a prevention of the induction of conditioned locomotion, but not of cocaine-induced sensitization.

  17. Cerebral Oedema, Blood-Brain Barrier Breakdown and the Decrease in Na(+),K(+)-ATPase Activity in the Cerebral Cortex and Hippocampus are Prevented by Dexamethasone in an Animal Model of Maple Syrup Urine Disease.

    Science.gov (United States)

    Rosa, Luciana; Galant, Leticia S; Dall'Igna, Dhébora M; Kolling, Janaina; Siebert, Cassiana; Schuck, Patrícia F; Ferreira, Gustavo C; Wyse, Angela T S; Dal-Pizzol, Felipe; Scaini, Giselli; Streck, Emilio L

    2016-08-01

    Maple syrup urine disease (MSUD) is a rare metabolic disorder associated with acute and chronic brain dysfunction. This condition has been shown to lead to macroscopic cerebral alterations that are visible on imaging studies. Cerebral oedema is widely considered to be detrimental for MSUD patients; however, the mechanisms involved are still poorly understood. Therefore, we investigated whether acute administration of branched-chain amino acids (BCAA) causes cerebral oedema, modifies the Na(+),K(+)-ATPase activity, affects the permeability of the blood-brain barrier (BBB) and alters the levels of cytokines in the hippocampus and cerebral cortex of 10-day-old rats. Additionally, we investigated the influence of concomitant administration of dexamethasone on the alterations caused by BCAA. Our results showed that the animals submitted to the model of MSUD exhibited an increase in the brain water content, both in the cerebral cortex and in the hippocampus. By investigating the mechanism of cerebral oedema, we discovered an association between H-BCAA and the Na(+),K(+)-ATPase activity and the permeability of the BBB to small molecules. Moreover, the H-BCAA administration increases Il-1β, IL-6 and TNF-α levels in the hippocampus and cerebral cortex, whereas IL-10 levels were decreased in the hippocampus. Interestingly, we showed that the administration of dexamethasone successfully reduced cerebral oedema, preventing the inhibition of Na(+),K(+)-ATPase activity, BBB breakdown and the increase in the cytokines levels. In conclusion, these findings suggest that dexamethasone can improve the acute cerebral oedema and brain injury associated with high levels of BCAA, either through a direct effect on brain capillary Na(+),K(+)-ATPase or through a generalized effect on the permeability of the BBB to all compounds.

  18. Portulaca oleracea L. prevents lipopolysaccharide-induced passive avoidance learning and memory and TNF-α impairments in hippocampus of rat.

    Science.gov (United States)

    Noorbakhshnia, Maryam; Karimi-Zandi, Leila

    2017-02-01

    There is a growing body of evidence that neuroinflammation can impair memory. It has been indicated that Portulaca oleracea Linn. (POL), possess anti-inflammatory activity and might improve memory disruption caused by inflammation. In this study the effect of pre-treatment with the hydro-alcoholic extract of POL on memory retrieval investigated in lipopolysaccharide (LPS) treated rats. Male Wistar rats (200-220g) received either a control diet or a diet containing of POL (400mg/kg, p.o.) for 14days. Then, they received injections of either saline or LPS (1mg/kg, i.p.). In all the experimental groups, 4h following the last injection, passive avoidance learning (PAL) and memory test was performed. The retention test was done 24h after the training and then the animals were sacrificed. Hippocampal TNF-α levels measured using ELISA as one criteria of LPS-induced neuroinflammation. The results indicated that LPS significantly impaired PAL and memory and increased TNF-α levels in hippocampus tissue. Pre-treatment with POL improved memory in control rats and prevented memory and TNF-α deterioration in LPS treated rats. Taken together, the results of this study suggest that the hydro-alcoholic extract of POL may improve memory deficits in LPS treated rats, possibly via inhibition of TNF-α and anti-inflammatory activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Effects of escitalopram and paroxetine on mTORC1 signaling in the rat hippocampus under chronic restraint stress.

    Science.gov (United States)

    Seo, Mi Kyoung; Choi, Cheol Min; McIntyre, Roger S; Cho, Hye Yeon; Lee, Chan Hong; Mansur, Rodrigo B; Lee, Yena; Lee, Jae-Hon; Kim, Young Hoon; Park, Sung Woo; Lee, Jung Goo

    2017-04-26

    Recent studies have suggested that the activation of mammalian target of rapamycin (mTOR) signaling may be related to antidepressant action. Therefore, the present study evaluated whether antidepressant drugs would exert differential effects on mTOR signaling in the rat hippocampus under conditions of chronic restraint stress. Male Sprague-Dawley rats were subjected to restraint stress for 6 h/days for 21 days with either escitalopram (10 mg/kg) or paroxetine (10 mg/kg) administered after the chronic stress procedure. Western blot analyses were used to assess changes in the levels of phospho-Ser2448-mTOR, phospho-Thr37/46-4E-BP-1, phospho-Thr389-p70S6 K, phospho-Ser422-eIF4B, phospho-Ser240/244-S6, phospho-Ser473-Akt, and phospho-Thr202/Tyr204-ERK in the hippocampus. Chronic restraint stress significantly decreased the levels of phospho-mTOR complex 1 (mTORC1), phospho-4E-BP-1, phospho-p70S6 K, phospho-eIF4B, phospho-S6, phospho-Akt, and phospho-ERK (p stress reduced phospho-mTORC1 signaling activities in general, while escitalopram and paroxetine prevented these changes in phospho-mTORC1 signaling activities. These findings provide further data that contribute to understanding the possible relationships among mTOR activity, stress, and antidepressant drugs.

  20. Transcript-specific effects of adrenalectomy on seizure-induced BDNF expression in rat hippocampus

    DEFF Research Database (Denmark)

    Lauterborn, J C; Poulsen, F R; Stinis, C T

    1998-01-01

    Activity-induced brain-derived neurotrophic factor (BDNF) expression is negatively modulated by circulating adrenal steroids. The rat BDNF gene gives rise to four major transcript forms that each contain a unique 5' exon (I-IV) and a common 3' exon (V) that codes for BDNF protein. Exon......-specific in situ hybridization was used to determine if adrenalectomy has differential effects on basal and activity-induced BDNF transcript expression in hippocampus. Adrenalectomy alone had only modest effects on BDNF mRNA levels with slight increases in exon III-containing mRNA with 7-10-day survival...... no effect on exon IV-containing mRNA content. These results demonstrate that the negative effects of adrenal hormones on activity-induced BDNF expression are by far the greatest for transcripts containing exons I and II. Together with evidence for region-specific transcript expression, these results suggest...

  1. The hippocampus is necessary for enhancements and impairments of learning following stress

    OpenAIRE

    Bangasser, Debra A; Shors, Tracey J

    2007-01-01

    The hippocampus is often considered to be an important site for stress and learning interactions; however, it has never been demonstrated whether these effects require the hippocampus. In the current study, hippocampal lesions prevented both enhancements of learning after stress in male rats and impairments of learning after stress in female rats without disrupting learning itself in either sex. Thus, the hippocampus is necessary for modifying learning in males and females after acute stressf...

  2. Regular Exercise Prevents Sleep Deprivation Associated Impairment of Long-Term Memory and Synaptic Plasticity in The CA1 Area of the Hippocampus

    Science.gov (United States)

    Zagaar, Munder; Dao, An; Levine, Amber; Alhaider, Ibrahim; Alkadhi, Karim

    2013-01-01

    Study Objectives: The present study aimed to investigate the effects of treadmill exercise on sleep deprivation (S-D)-induced impairment of hippocampal dependent long-term memory, late phase long-term potentiation (L-LTP) and its signaling cascade in the cornu ammonis 1 (CA1) area. Experimental Design: Animals were conditioned to run on treadmills for 4 weeks then deprived of sleep for 24 h using the columns-in-water method. We tested the effect of exercise and/or S-D on behavioral performance using a post-learning paradigm in the radial arm water maze (RAWM) and in vivo extracellular recording in the CA1 area. The levels of L-LTP-related molecules in the CA1 area were then assessed both before and after L-LTP induction. Measurements and Results: After 24 h of S-D, spatial long-term memory impairment in the RAWM and L-LTP suppression was prevented by 4 weeks of regular exercise. Regular exercise also restored the S-D-associated decreases in the basal levels of key signaling molecules such as: calcium/calmodulin kinase IV (CaMKIV), mitogen-activated protein kinase (MAPK/ERK), phosphorylated cAMP response element-binding protein (P-CREB) and brain derived neurotrophic factor (BDNF), in the CA1 area. After L-LTP induction, regular exercise also prevented the S-D-induced down regulation of BDNF and P-CREB protein levels. Conclusions: The results suggest that our exercise protocol may prevent 24-h S-D-induced impairments in long-term memory and LTP by preventing deleterious changes in the basal and post-stimulation levels of P-CREB and BDNF associated with S-D. Citation: Zagaar M; Dao A; Levine A; Alhaider I; Alkadhi K. Regular exercise prevents sleep deprivation associated impairment of long-term memory and synaptic plasticity in the CA1 area of the hippocampus. SLEEP 2013;36(5):751-761. PMID:23633758

  3. Differential effects of duration and age on the consequences of neuroinflammation in the hippocampus.

    Science.gov (United States)

    Bardou, Isabelle; Brothers, Holly M; Kaercher, Roxanne M; Hopp, Sarah C; Wenk, Gary L

    2013-10-01

    The current study investigated the hypothesis that the duration of the proinflammatory environment plays a critical role in the brain's response that results in negative consequences on cognition, biochemistry, and pathology. Lipopolysaccharide or artificial cerebrospinal fluid was slowly (250 ηg/h) infused into the fourth ventricle of young (3-month-old), adult (9-month-old), or aged (23-month-old) male F-344 rats for 21 or 56 days. The rats were then tested in the water pool task and endogenous hippocampal levels of pro- and anti-inflammatory proteins and genes and indicators of glutamatergic function were determined. The duration of the lipopolysaccharide infusion, compared with the age of the rat, had the greatest effect on (1) spatial working memory; (2) the density and distribution of activated microglia within the hippocampus; and (3) the cytokine protein and gene expression profiles within the hippocampus. The duration- and age-dependent consequences of neuroinflammation might explain why human adults respond positively to anti-inflammatory therapies and aged humans do not. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Effects of acute phencyclidine administration on arginine metabolism in the hippocampus and prefrontal cortex in rats.

    Science.gov (United States)

    Knox, Logan T; Jing, Yu; Collie, Nicola D; Zhang, Hu; Liu, Ping

    2014-06-01

    Phencyclidine (PCP), a non-competitive N-methyl-d-aspartate glutamate receptor antagonist, induces schizophrenic symptoms in healthy individuals, and altered arginine metabolism has been implicated in schizophrenia. The present study investigated the effects of a single subcutaneous injection of PCP (2, 5 or 10 mg/kg) on arginine metabolism in the sub-regions of the hippocampus and prefrontal cortex in male young adult Sprague-Dawley rats. Animals' general behaviour was assessed in the open field apparatus 30 min after the treatment, and the brain tissues were collected at the time point of 60 min post-treatment. Behaviourally, PCP resulted in reduced exploratory activity in a dose-dependent manner, and severe stereotype behaviour and ataxia at the highest dose. Neurochemically, PCP significantly altered the nitric oxide synthase and arginase activities, the l-arginine, agmatine, spermine, glutamate and GABA levels, and the glutamine/glutamate and glutamate/GABA ratios in a dose-dependent and/or region-specific manner. Cluster analyses showed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which changed as a function of PCP mainly in the hippocampus. Multiple regression analysis revealed significant neurochemical-behavioural correlations. These results demonstrate, for the first time, that a single acute administration of PCP affects animals' behaviour and arginine metabolism in the brain. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. ANI inactivation: unconditioned anxiolytic effects of anisomycin in the ventral hippocampus.

    Science.gov (United States)

    Greenberg, Anastasia; Ward-Flanagan, Rachel; Dickson, Clayton T; Treit, Dallas

    2014-11-01

    Although hippocampal function is typically described in terms of memory, recent evidence suggests a differentiation along its dorsal/ventral axis, with dorsal regions serving memory and ventral regions serving emotion. While long-term memory is thought to be dependent on de novo protein synthesis because it is blocked by translational inhibitors such as anisomycin (ANI), online (moment-to-moment) functions of the hippocampus (such as unconditioned emotional responding) should not be sensitive to such manipulations since they are unlikely to involve neuroplasticity. However, ANI has recently been shown to suppress neural activity which suggests (1) that protein synthesis is critical for neural function and (2) that paradigms using ANI are confounded by its inactivating effects. We tested this idea using a neurobehavioral assay which compared the influence of intrahippocampal infusions of ANI at dorsal and ventral sites on unconditioned emotional behavior of rats. We show that ANI infusions in ventral, but not dorsal, hippocampus produced a suppression of anxiety-related responses in two well-established rodent tests: the elevated plus maze and shock-probe burying tests. These results are similar to those previously observed when ventral hippocampal activity is directly suppressed (e.g., by using sodium channel blockers). The present study offers compelling behavioral evidence for the proposal that ANI adversely affects ongoing neural function and therefore its influence is not simply limited to impairing the consolidation of long-term memories Copyright © 2014 Wiley Periodicals, Inc.

  6. Effect of thyroxine on munc-18 and syntaxin-1 expression in dorsal hippocampus of adult-onset hypothyroid rats

    Directory of Open Access Journals (Sweden)

    Y. Zhu

    2012-05-01

    Full Text Available Adult-onset hypothyroidism induces a variety of impairments on hippocampus- dependent neurocognitive functioningin which many synaptic proteins in hippocampus neurons are involved. Here, we observed the effect of adult-onset hypothyroidism on the expression of syntaxin-1 and munc-18 in the dorsal hippocampus and whether the altered proteins could be restored by levothyroxine (T4 treatment. All rats were separated into 4 groups randomly: hypothyroid group, 5μg T4/100 g body weight (BW treated group, 20 μg T4/100g BW treated group and control group. The radioimmunoassay kits were applied to assay the levels of serum T3 and T4, and the levels of syntaxin-1 and munc-18 in hippocampus were assessed by immunohistochemistry and Western blot. Both analysis corroborated that syntaxin-1 in the hypothyroid group was significantly higher. Munc-18 was lower in four layers of CA3 and dentate gyrus by immunohistochemistry. After two weeks of treatment with 5 μg T4/100g BW for hypothyroidism, syntaxin-1 levels were completely restored, whereas the recovery of munc-18 only located in two of the four impaired layers. Twenty μg T4/100g BW treatment normalized munc-18 levels. These data suggested that adult-onset hypothyroidism induced increment of syntaxin-1 and decrement of munc-18 in the dorsal hippocampus, which could be restored by T4 treatment. Larger dosage of T4 caused more effective restorations.

  7. Zuogui Jiangtang Jieyu Formulation Prevents Hyperglycaemia and Depressive-Like Behaviour in Rats by Reducing the Glucocorticoid Level in Plasma and Hippocampus

    Directory of Open Access Journals (Sweden)

    YuHong Wang

    2015-01-01

    Full Text Available Aim. To determine whether Zuogui Jiangtang Jieyu prescription (ZGJTJY has hypoglycemic and antidepressant effects which are mediated by corticosterone through adjustment of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 and glucocorticoid (GR levels. Materials and Methods. The diabetes-related depression rats were randomly divided into four groups: the model group, metformin (1.8 mg/kg combined with fluoxetine (10.8 mg/kg group, and ZGJTJY high and low dose groups. Four weeks after modeling, blood glucose, behavior, and cognitive function of depression were detected. The expressions of 11β-HSD1 and GR in hippocampus were measured by western blotting and immunohistochemical experiments. Results. We found that (1 the treatment with ZGJTJY (10.26 g/kg increases the motor activities and improves cognition ability. (2 ZGJTJY (10.26 g/kg significantly relieves the disorder in blood and the relative indexes. (3 ZGJTJY (10.26 g/kg can reduce hippocampal corticosterone expression levels and further improve hippocampus pathological changes. (4 ZGJTJY increased the expression of GR accompanied with decreasing 11β-HSD1 in hippocampus. Conclusions. ZGJTJY inhibits the expression of 11β-HSD1 and increases GR in hippocampus and subsequently modulates blood glucose levels, and therefore it is potential property that ZGJTJY could be of benefit for the treatment of behavior and cognitive function of diabetes-related depression.

  8. Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus

    Science.gov (United States)

    Title (20 words): Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus. Introduction (120 words): Polybrominated diphenyl ethers (PBDE5) possess neurotoxic effects similar to those of PCBs. The cellular a...

  9. The Effect of Morphine on Low Mg2+ ACSF Induced Epileptiform Activity in Mice Whole Hippocampus

    Directory of Open Access Journals (Sweden)

    B. Heshmatian

    2008-10-01

    Full Text Available Introduction & Objective: Morphine has both anti and proconvulsive actions on the epileptiform activity depending on the exact experimental conditions. Study of the contraversy effects of morphine on certain neural activities such as epilepsy leads to clearify some neural events and neuronal adaptations. This study was designed to determine the effect of morphine on seizure induced by Low Mg2+ Artificial Cerebrospinal Fluid (ACSF in whole hippocampus preparation of mice. Materials & Methods: C57/BL6 mice 11 to 19 days of age, were used. Animals anaesthetized and the brain was removed(n=25 and placed in ice-cold, continuously oxygenated ACSF for 3 min. Then the hippocampi were dissected and incubated in normal ACSF at room temperature for an hour before electrophysiologic recording. Seizure activity was induced by per fusing the hippocampus with Low Mg2+ ACSF. Extra cellular recordings were performed mainly in the CA1 pyramidal cell layer. Seizure activity was quantified by measuring the duration and number of the ictal events and the percent of seizure time. Results: Both low and high doses of morphine(10, 200μM, respectively suppressed seizure length and percent of seizure time, whereas moderate doses of morphine (30,100 μM potentates them. Naloxone (10μM not only inhibited the excitatory effects of morphine on seizure but also suppressed the Low Mg2+ ACSF induced epileptiform activities. Combined application of morphine and naloxone attenuated the seizure.Conclusion: Our results indicate that morphine in moderate concentration of 30 and 100 μM may potentate seizure activity and it should be used with caution in epileptic patients, while naloxone has anticonvulsant actions and can probably be used in clinical trials especially to control temporal lob epilepsy.

  10. Inactivation of the dorsal hippocampus or the medial prefrontal cortex impairs retrieval but has differential effect on spatial memory reconsolidation.

    Science.gov (United States)

    Rossato, Janine I; Köhler, Cristiano A; Radiske, Andressa; Bevilaqua, Lia R M; Cammarota, Martín

    2015-11-01

    Active memories can incorporate new information through reconsolidation. However, the notion that memory retrieval is necessary for reconsolidation has been recently challenged. Non-reinforced retrieval induces hippocampus and medial prefrontal cortex (mPFC)-dependent reconsolidation of spatial memory in the Morris water maze (MWM). We found that the effect of protein synthesis inhibition on this process is abolished when retrieval of the learned spatial preference is hindered through mPFC inactivation but not when it is blocked by deactivation of dorsal CA1. Our results do not fully agree with the hypothesis that retrieval is unneeded for reconsolidation. Instead, they support the idea that a hierarchic interaction between the hippocampus and the mPFC controls spatial memory in the MWM, and indicate that this cortex is sufficient to retrieve the information essential to reconsolidate the spatial memory trace, even when the hippocampus is inactivated. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Tramadol Pretreatment Enhances Ketamine-Induced Antidepressant Effects and Increases Mammalian Target of Rapamycin in Rat Hippocampus and Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Chun Yang

    2012-01-01

    Full Text Available Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST. Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.

  12. Neuroprotective effect of olive oil in the hippocampus CA1 neurons following ischemia: Reperfusion in mice

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    M Zamani

    2013-01-01

    Full Text Available Introduction: Transient global ischemia induces selective, delayed neuronal death of pyramidal neurons in the hippocampal CA1. Oxidative Stress is considered to be involved in a number of human diseases including ischemia. Preliminary studies confirmed reduction of cell death in brain following treatment with antioxidants. Aim: According to this finding, we study the relationship between consumption of olive oil on cell death and memory disorder in brain ischemia. We studied the protective effect of olive oil against ischemia-reperfusion. Material and Methods: Experimental design includes three groups: Intact (n = 8, ischemic control (n = 8 and treatment groups with olive oil (n = 8. The mice treated with olive oil as pre-treatment for a week. Then, ischemia induced by common carotid artery ligation and following the reduction of inflammation [a week after ischemia], the mice post-treated with olive oil. Nissl staining applied for counting necrotic cells in hippocampus CA1. Tunnel kit was used to quantify apoptotic cell death while to short term memory scale, we apply y-maze and shuttle box tests and for detection the rate of apoptotic and treated cell, we used western blotting test for bax and bcl2 proteins. Results: High rate of apoptosis was seen in ischemic group that significantly associated with short-term memory loss. Cell death was significantly lower when mice treated with olive oil. The memory test results were adjusted with cell death results and bax and bcl2 expression in all groups′ comparison. Ischemia for 15 min induced cell death in hippocampus with more potent effect on CA1. Conclusion: Olive oil intake significantly reduced cell death and decreased memory loss.

  13. Effects of inflammation on hippocampus and substantia nigra responses to novelty in healthy human participants.

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

    2015-03-01

    Humans are naturally inquisitive. This tendency is adaptive, aiding identification of potentially valuable novel outcomes. The dopaminergic substantia nigra (SN) is implicated in the drive to explore novel stimuli and situations. However, infection and inflammation inhibit the motivation to seek out novelty. This likely serves to limit exposure to uncertain, potentially detrimental outcomes when metabolic resources are limited. Nevertheless, the neural mechanisms through which inflammation constrains novelty seeking are poorly understood. We therefore scanned 16 healthy participants (6 male, mean 27.2±7.3 years), using fMRI, once following experimental inflammation (intramuscular (i.m.) typhoid vaccination) and once after placebo (i.m. saline), with the aim of characterizing effects of inflammation on neural processing of novel and familiar place, and face stimuli. We specifically tested the effects of inflammation on the hypothesized roles of SN and hippocampus in novelty processing. Typhoid vaccination evoked a nearly threefold increase in circulating pro-inflammatory cytokine (interleukin-6) levels 3 h after injection, indicating induction of mild systemic inflammation. Enhanced hippocampal responses to novel (compared with familiar) stimuli were observed following both vaccine and placebo, consistent with intact central novelty detection. However, the normal bilateral reactivity of SN to stimulus novelty was significantly attenuated following inflammation. Correspondingly, inflammation also markedly impaired novelty-related functional coupling between the SN and hippocampus. These data extend previous findings of SN sensitivity to mild inflammation associated with changes in psychomotor responding, and suggest that inflammation-induced blunting of SN responses to hippocampal novelty signals may represent a plausible mechanism through which inflammation impairs motivational responses to novelty.

  14. [Effect of electroacupuncture on cellular structure of hippocampus in splenic asthenia pedo-rats].

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    Yang, Zhuo-xin; Zhuo, Yuan-yuan; Yu, Hai-bo; Wang, Ning

    2010-02-01

    To observe the effect of electroacupuncture (EA) on hippocampal structure in splenic asthenia pedo-rats. A total of 15 SD male rats were randomly assigned to normal control group (n=5), model group (n=5) and EA group (n=5). Splenic asthenic syndrome model was established by intragastric administration of rhubarb and intraperitoneal injection of Reserpine for 14 d. EA (1 mA, 3 Hz/iS Hz) was applied to bilateral "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) for 20 mm, once a day for 14 days. The cellular structure of hippocampus was observed by light microscope and transmission electron microscope. Optical microscopic observation showed that in normal control group, the cellular nucleus was distinct, and the granular cell layer well-arranged and tight. In model group, the intracellular space was widened, and the granular cell layer was out of order in the arrangement. In EA group, the celluldr nucleus and the granular cell layer were nearly normal. Results of the electronic microscope showed that cells in model group had a karyopyknosis with irregular appearance and clear incisure, and some of them presented dissolving and necrotic phenomena; and those in EA group were milder in injury, had nearly-normal nucleus with visible nucleoli and relatively-intact nuclear membrane. Regarding the cellular plasma, in comparison with rich normal organelles of control group, the mitochondria in model group were swelling, with vague, dissolved and broken cristae, while in EA group, majority of the organelles were well-kept, and slightly dissolved mitochondrial cristae found. In regard to the synaptic structure, in comparison with control group, synaptic apomorphosis and swelling mitochondria were found in model group While in EA group, milder swelling and hydropic degeneration were seen. Different from the distinct pre- and post-synaptic membrane and synaptic vesicles of control group, while those in EA group were nearly-normal. electroacupunture can effectively relieve splenasthenic

  15. [Effects of huannao yicong formula extract on behavior and ultrastructure of hippocampus mitochondria of APP transgenic mice of different months].

    Science.gov (United States)

    Liu, Mingfang; Li, Hao; Liu, Jian'gang; Liu, Longtao; Guan, Jie; Cai, Linlin; Hu, Jia; Wei, Yun

    2012-03-01

    To study the effects of Huannao Yicong formula (HNYCF) extract on behavior and ultrastructure of mitochondria in hippocampus CA1 area of APP transgenic mice of different months, and explore its partial mechanism in treating Alzheimer's disease (AD) through the perspective of energy metabolism. One hundred and twenty APP695V717I transgenic mice of 3-month old were divided randomly into model group, Donepezil group (0.65 x 10(-3) g x kg(-1) x d(-1)), HNYCF extract large dose group (2.8 g x kg(-1) x d(-1)) and HNYCF extract small dose group (1.4 g x kg(-1) x d(-1)), and 30 mice in each group. Another 30 C57BL/6J mice with the same age and background were used as normal control group. All animals were administered once daily by gavage with the corresponding drug or distilled water. The course of intervention was 4 and 6 months. Behavioral changes were observed by Morris water maze test and step down test. Ultrastructure of mitochondria in hippocampus CA1 area was observed by transmission electron microscope. At the age of 7 and 9 month, the number of times of passing through platform, swimming time and path length of model group increased significantly (P mitochondrial of hippocampus CA1 area was disrupted and dissolved. Most ridge structure arranged in a mess, and some ridge showed expanding, matrix loosing and swollen appearance, and it would get worse with the development of disease course. HNYCF extract could improve ultrastructure of mitochondria in hippocampus CA1 area, and increase its quality. Learning and memory ability decreased in APP transgenic mice model, and the quantity of neural mitochondria in hippocampus CA1 area with structure disrupting, and it would get worse with the development of disease course. HNYCF extract could improve the learning and memory ability of APP transgenic mice model, its mechanism might relate with improving ultrastructure of mitochondria in hippocampus, and increasing its quantity.

  16. Nicotine?prevented learning and memory impairment in REM sleep?deprived rat is modulated by DREAM protein in the hippocampus

    OpenAIRE

    Abd Rashid, Norlinda; Hapidin, Hermizi; Abdullah, Hasmah; Ismail, Zalina; Long, Idris

    2017-01-01

    Abstract Introduction REM sleep deprivation is associated with impairment in learning and memory, and nicotine treatment has been shown to attenuate this effect. Recent studies have demonstrated the importance of DREAM protein in learning and memory processes. This study investigates the association of DREAM protein in REM sleep?deprived rats hippocampus upon nicotine treatment. Methods Male Sprague Dawley rats were subjected to normal condition, REM sleep deprivation and control wide platfor...

  17. Caffeine Consumption Prevents Diabetes-Induced Memory Impairment and Synaptotoxicity in the Hippocampus of NONcZNO10/LTJ Mice

    OpenAIRE

    Duarte, João M. N.; Agostinho, Paula M.; Carvalho, Rui A.; Cunha, Rodrigo A.

    2012-01-01

    Diabetic conditions are associated with modified brain function, namely with cognitive deficits, through largely undetermined processes. More than understanding the underlying mechanism, it is important to devise novel strategies to alleviate diabetes-induced cognitive deficits. Caffeine (a mixed antagonist of adenosine A(1) and A(2A) receptors) emerges as a promising candidate since caffeine consumption reduces the risk of diabetes and effectively prevents memory deficits caused by different...

  18. Caffeine consumption prevents memory impairment, neuronal damage, and adenosine A2A receptors upregulation in the hippocampus of a rat model of sporadic dementia.

    Science.gov (United States)

    Espinosa, Janaína; Rocha, Andreia; Nunes, Fernanda; Costa, Marcelo S; Schein, Vanessa; Kazlauckas, Vanessa; Kalinine, Eduardo; Souza, Diogo O; Cunha, Rodrigo A; Porciúncula, Lisiane O

    2013-01-01

    Intracerebroventricular (icv) streptozotocin (STZ) administration induces pathological and behavioral alterations similar to those observed in Alzheimer's disease (AD) and is thus considered an experimental model of sporadic AD. Since caffeine (an adenosine receptor antagonist) and selective antagonists of adenosine A2A receptors modify the course of memory impairment in different amyloid-β-based experimental models of AD, we now tested the impact of caffeine on STZ-induced dementia and associated neurodegeneration in the hippocampus as well as on the expression and density of adenosine receptors. Adult male rats received a bilateral infusion of saline or STZ (3 mg/kg, icv), which triggered memory deficits after four weeks, as gauged by impaired object recognition memory. This was accompanied by a reduced NeuN immunoreactivity in the hippocampal CA1 region and an increased expression and density of adenosine A2A receptors (A2AR), but not A1R, in the hippocampus. Caffeine consumption (1 g/L in the drinking water starting 2 weeks before the STZ challenge) prevented the STZ-induced memory impairment and neurodegeneration as well as the upregulation of A2AR. These findings provide the first demonstration that caffeine prevents sporadic dementia and implicate the control of central A2AR as its likely mechanism of action.

  19. Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat

    Science.gov (United States)

    Blanco-Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodriguez de Fonseca, Fernando

    2014-01-01

    Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2′-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned

  20. In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus

    OpenAIRE

    Raman, Lakshmi; Tkac, Ivan; Ennis, Kathleen; Georgieff, Michael K.; Gruetter, Rolf; Rao, Raghavendra

    2005-01-01

    The cognitive deficits observed in children with cyanotic congenital heart disease suggest involvement of the developing hippocampus. Chronic postnatal hypoxia present during infancy in these children may play a role in these impairments. To understand the biochemical mechanisms of hippocampal injury in chronic hypoxia, a neurochemical profile consisting of 15 metabolite concentrations and 2 metabolite ratios in the hippocampus was evaluated in a rat model of chronic postnatal hypoxia using i...

  1. [Effects of noise exposure on event-related potential P300 and mechanism in hippocampus of rats].

    Science.gov (United States)

    Cui, Bo; Wu, Ming-quan; She, Xiao-jun; Liu, Hong-tao

    2009-08-01

    To study the effects of noise on event-related potential(ERP) and its mechanism in hippocampus in rats. Male SD rats were divided into 2 groups: control group (CG) and noise exposure group(NG). The rats in NG were exposed to white noise 105 dB SPL for 2.5 h/d x 20 d. P300 were recorded at parietal bone in rats. The Nissl body, NMDAR2B and [Ca2+]i of neurons in hippocampus were analyzed. The peak latency (PL) of ERP P3a, P3 and P3b in NG were significantly longer than that in CG in the 14th and 20th exposure day. The amount of Nissl body in dentate gyrus (DG) and CA1 region and NMDAR2B in DG, CA1 and CA3 region of hippocampus of NG were significantly decreased than those of CG as well, while the concentration of Ca2+ in neurons increased markedly in NG. Decreased Nissl body and NMDAR2B and increased [Ca2+]i in hippocampus in long-term noise exposed rats might cause the change of ERP P300.

  2. Long Term Depression in Rat Hippocampus and the Effect of Ethanol during Fetal Life

    Directory of Open Access Journals (Sweden)

    Olivier Pierrefiche

    2017-11-01

    Full Text Available Alcohol (ethanol disturbs cognitive functions including learning and memory in humans, non-human primates, and laboratory animals such as rodents. As studied in animals, cellular mechanisms for learning and memory include bidirectional synaptic plasticity, long-term potentiation (LTP, and long-term depression (LTD, primarily in the hippocampus. Most of the research in the field of alcohol has analyzed the effects of ethanol on LTP; however, with recent advances in the understanding of the physiological role of LTD in learning and memory, some authors have examined the effects of ethanol exposure on this particular signal. In the present review, I will focus on hippocampal LTD recorded in rodents and the effects of fetal alcohol exposure on this signal. A synthesis of the findings indicates that prenatal ethanol exposure disturbs LTD concurrently with LTP in offspring and that both glutamatergic and γ-aminobutyric acid (GABA neurotransmissions are altered and contribute to LTD disturbances. Although the ultimate mode of action of ethanol on these two transmitter systems is not yet clear, novel suggestions have recently appeared in the literature.

  3. Anticonvulsant and neuroprotective effects of Rosa damascena hydro-alcoholic extract on rat hippocampus.

    Science.gov (United States)

    Homayoun, Mansour; Seghatoleslam, Masoumeh; Pourzaki, Mojtaba; Shafieian, Reihaneh; Hosseini, Mahmoud; Ebrahimzadeh Bideskan, Alireza

    2015-01-01

    Previously, analgesic, hypnotic, and anticonvulsant effects have been suggested for Rosa damascena (R. damascena). In the present study, possible anti-seizure and neuro-protective effects of hydro-alcoholic extract of R. damascena has been investigated after inducing seizures in rats by pentylenetetrazole (PTZ). The rats were divided to five groups: (1) CONTROL: received saline, (2) PTZ: 100 mg/kg, i.p., (3) PTZ- Extract 50 mg/kg (PTZ-Ext 50), (4) PTZ- Extract 100 mg/kg (PTZ-Ext 100), and (5) PTZ- Extract 200 mg/kg (PTZ-Ext 200) groups which were treated with 50, 100, and 200 mg/kg respectively of hydro-alcoholic extract of R. dam ascena for one week before PTZ injection. The animals were examined for electrocorticography (ECoG) recording and finally, the brains were removed for histological study. The hydro-alcoholic extract of R. dam ascena significantly prolonged the latency of seizure attacks and reduced the frequency and amplitude of epileptiform burst discharges induced by PTZ injection. Moreover, all three doses of the extract significantly inhibited production of dark neurons in different regions of the hippocampus in the mentioned animal model. The present study showed that the hydro-alcoholic extract of R. dam ascena has anticonvulsant and neuroprotective effects. More investigations are needed to be done in order to better understand the responsible compound(s) as well as the possible mechanism(s).

  4. Anticonvulsant and neuroprotective effects of Rosa damascena hydro-alcoholic extract on rat hippocampus

    Directory of Open Access Journals (Sweden)

    Mansour Homayoun

    2015-04-01

    Full Text Available Objective: Previously, analgesic, hypnotic, and anticonvulsant effects have been suggested for Rosa damascena (R. damascena. In the present study, possible anti-seizure and neuro-protective effects of hydro-alcoholic extract of R. damascena has been investigated after inducing seizures in rats by pentylenetetrazole (PTZ. Materials and Methods: The rats were divided to five groups: (1 Control: received saline, (2 PTZ: 100 mg/kg, i.p., (3 PTZ-Extract 50 mg/kg(PTZ-Ext 50, (4 PTZ- Extract 100 mg/kg(PTZ-Ext 100, and (5 PTZ- Extract 200 mg/kg(PTZ-Ext 200 groups which were treated with 50, 100, and 200 mg/kg respectively of hydro-alcoholic extract of R. damascena for one week before PTZ injection. The animals were examined for electrocorticography (ECoG recording and finally, the brains were removed for histological study. Results: The hydro-alcoholic extract of R. damascena significantly prolonged the latency of seizure attacks and reduced the frequency and amplitude of epileptiform burst discharges induced by PTZ injection. Moreover, all three doses of the extract significantly inhibited production of dark neurons in different regions of the hippocampus in the mentioned animal model. Conclusion: The present study showed that the hydro-alcoholic extract of R. damascena has anticonvulsant and neuroprotective effects. More investigations are needed to be done in order to better understand the responsible compound(s as well as the possible mechanism(s.

  5. The ROCK Inhibitor Fasudil Prevents Chronic Restraint Stress-Induced Depressive-Like Behaviors and Dendritic Spine Loss in Rat Hippocampus.

    Science.gov (United States)

    García-Rojo, Gonzalo; Fresno, Cristóbal; Vilches, Natalia; Díaz-Véliz, Gabriela; Mora, Sergio; Aguayo, Felipe; Pacheco, Aníbal; Parra-Fiedler, Nicolás; Parra, Claudio S; Rojas, Paulina S; Tejos, Macarena; Aliaga, Esteban; Fiedler, Jenny L

    2017-04-01

    Dendritic arbor simplification and dendritic spine loss in the hippocampus, a limbic structure implicated in mood disorders, are assumed to contribute to symptoms of depression. These morphological changes imply modifications in dendritic cytoskeleton. Rho GTPases are regulators of actin dynamics through their effector Rho kinase. We have reported that chronic stress promotes depressive-like behaviors in rats along with dendritic spine loss in apical dendrites of hippocampal pyramidal neurons, changes associated with Rho kinase activation. The present study proposes that the Rho kinase inhibitor Fasudil may prevent the stress-induced behavior and dendritic spine loss. Adult male Sprague-Dawley rats were injected with saline or Fasudil (i.p., 10 mg/kg) starting 4 days prior to and maintained during the restraint stress procedure (2.5 h/d for 14 days). Nonstressed control animals were injected with saline or Fasudil for 18 days. At 24 hours after treatment, forced swimming test, Golgi-staining, and immuno-western blot were performed. Fasudil prevented stress-induced immobility observed in the forced swimming test. On the other hand, Fasudil-treated control animals showed behavioral patterns similar to those of saline-treated controls. Furthermore, we observed that stress induced an increase in the phosphorylation of MYPT1 in the hippocampus, an exclusive target of Rho kinase. This change was accompanied by dendritic spine loss of apical dendrites of pyramidal hippocampal neurons. Interestingly, increased pMYPT1 levels and spine loss were both prevented by Fasudil administration. Our findings suggest that Fasudil may prevent the development of abnormal behavior and spine loss induced by chronic stress by blocking Rho kinase activity.

  6. Effects of duloxetine on microRNA expression profile in frontal lobe and hippocampus in a mouse model of depression.

    Science.gov (United States)

    Pan, Bing; Liu, Yamei

    2015-01-01

    Depression is a major mood disorder affecting people worldwide. The posttranscriptional gene regulation mediated by microRNAs (miRNAs) which may have critical roles in the pathogenesis of depression. However, to date, little is known about the effects of the antidepressant drug duloxetine on miRNA expression profile in chronic unpredictable mild stress (CUMS)-induced depression model in mice. Healthy adult male Kunming mice were randomly divided into three groups: control group, model group and duloxetine group. Sucrose preference test and open field test were used to represent the behavioral change. MiRNAs levels in frontal lobe and hippocampus of mice were analyzed using miRNA microarrays assay. We observed that long-term treatment with duloxetine significantly ameliorated the CUMS procedure-induced sucrose preference decreases and mice treated with duloxetine demonstrated a reversal of the number of crossings, and rearings reduced by CUMS. A significant upregulation of miR-132 and miR-18a in hippocampus in the duloxetine treatment group compared with model group, whereas the levels of miR-134 and miR-124a were significantly downregulated. Furthermore, miR-18a showed significant upregulation in frontal lobe in the duloxetine treatment group relative to model group. Our data showed that miRNA expression profile in frontal lobe and hippocampus was affected by duloxetine in mice model of depression. The effect was especially pronounced in the hippocampus, suggesting that hippocampus might be the action site of duloxetine, which presumably worked by regulating the expression of miRNA levels.

  7. The effect of mitochondrial calcium uniporter on mitochondrial fission in hippocampus cells ischemia/reperfusion injury

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    Zhao, Lantao; Li, Shuhong; Wang, Shilei, E-mail: wshlei@aliyun.com; Yu, Ning; Liu, Jia

    2015-06-05

    The mitochondrial calcium uniporter (MCU) transports free Ca{sup 2+} into the mitochondrial matrix, maintaining Ca{sup 2+} homeostasis, thus regulates the mitochondrial morphology. Previous studies have indicated that there was closely crosstalk between MCU and mitochondrial fission during the process of ischemia/reperfusion injury. This study constructed a hypoxia reoxygenation model using primary hippocampus neurons to mimic the cerebral ischemia/reperfusion injury and aims to explore the exactly effect of MCU on the mitochondrial fission during the process of ischemia/reperfusion injury and so as the mechanisms. Our results found that the inhibitor of the MCU, Ru360, decreased mitochondrial Ca{sup 2+} concentration, suppressed the expression of mitochondrial fission protein Drp1, MIEF1 and Fis1, and thus improved mitochondrial morphology significantly. Whereas spermine, the agonist of the MCU, had no significant impact compared to the I/R group. This study demonstrated that the MCU regulates the process of mitochondrial fission by controlling the Ca{sup 2+} transport, directly upregulating mitochondrial fission proteins Drp1, Fis1 and indirectly reversing the MIEF1-induced mitochondrial fusion. It also provides new targets for brain protection during ischemia/reperfusion injury. - Highlights: • We study MCU with primary neuron culture. • MCU induces mitochondrial fission. • MCU reverses MIEF1 effect.

  8. Neuroplasticity in the maternal hippocampus: Relation to cognition and effects of repeated stress.

    Science.gov (United States)

    Pawluski, Jodi L; Lambert, Kelly G; Kinsley, Craig H

    2016-01-01

    This article is part of a Special Issue "Parental Care". It is becoming clear that the female brain has an inherent plasticity that is expressed during reproduction. The changes that occur benefit the offspring, which in turn secures the survival of the mother's genetic legacy. Thus, the onset of maternal motivation involves basic mechanisms from genetic expression profiles, to hormone release, to hormone-neuron interactions, all of which fundamentally change the neural architecture - and for a period of time that extends, interestingly, beyond the reproductive life of the female. Although multiple brain areas involved in maternal responses are discussed, this review focuses primarily on plasticity in the maternal hippocampus during pregnancy, the postpartum period and well into aging as it pertains to changes in cognition. In addition, the effects of prolonged and repeated stress on these dynamic responses are considered. The maternal brain is a marvel of directed change, extending into behaviors both obvious (infant-directed) and less obvious (predation, cognition). In sum, the far-reaching effects of reproduction on the female nervous system provide an opportunity to investigate neuroplasticity and behavioral flexibility in a natural mammalian model. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. The effect of alcoholic extract of Panicum miliaceum L. seed on hippocampus neuronal density in male mouse

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    Arezoo Bornarodi

    2017-08-01

    Full Text Available Background: Hippocampus organization is a part of temporal lobe, which consists of several sections including hippocampal body, dentate gyrus and subiculum. Panicum miliaceum L. contains proteins, vitamins and antioxidants for human health. This study was conducted to examine the effect of the alcoholic extract of the seed of Panicum miliaceum L. plant on hippocampus neuronal density. Materials and Methods: In this experimental study, 24 male mice were divided into 4 groups (n=6, each group. The alcoholic extract of the seed of the Panicum miliaceum L. plant was prepared by soxhlet extraction. Three doses of the extract 25, 50, 75 mg/kg were intraperitoneally injected to 3 treatment groups for 21 days and the control group received normal saline injection. At the end of the experiment, the animals were anesthetized and after perfusion, their brains were removed from the skull. After tissue processing, slices of the brain were prepared and stained. Then, different regions of the hippocampus were photographed and neuronal densities were evaluated. Results: Results showed that the neuronal density in the CA1, CA3 regions of the group treated with 50 mg/kg of the alcoholic extract and in all regions of hippocampus (CA1,CA2,CA3 in groups treated with dose of 75 mg/kg of the alcoholic extract had a significant increase compared to the control group (P<0.05. Conclusion: The present study shows that the alcoholic extract of the seed of Panicum miliaceum L. plant increases neuronal density and induces neurogenesis in the mouse hippocampus.

  10. Differential effects of benzodiazepines on phospholipid methylation in hippocampus and cerebellum of rats

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    Tacconi, M.T.; Salmona, M.

    1988-01-01

    To elucidate the relationship between the occupancy of BDZ binding sites and phospholipid methylation in brain, the authors examined phosphatidylethanolamine-N-methyltransferase (PEMT) activity in synaptosomes of rat hippocampi and cerebella in the presence of BDZ ligands with different modes of action. We found that Ro 5-4864, a specific ligand for peripheral type receptors, increased PL methylation in hippocampal and cerebellar synaptosomes. This effect was directly related to receptor occupancy, since the specific antagonist PK11195 inhibited the rise in PEMT activity induced by Ro 5-4864. Clonazepam, on the other hand, tended to reduce PL production in cerebellum and hippocampus except for hiccocampal (/sup 3/H)-phosphatidyl-N-monomethylethanolamine which was elevated by 40 to 70% at doses ranging from 10/sup -9/ to 10/sup -6/M. When equimolar concentrations of the antagonist Ro 15-1788 were given in association the clonazepam-induced phosphatidyl-N-monomethylethanolamine increase was reduced by 70%. These data support the involvement of structural and functional membrane alterations in the action of BDZ. 20 references, 2 figures, 2 tables.

  11. Associative recognition and the hippocampus: differential effects of hippocampal lesions on object-place, object-context and object-place-context memory.

    Science.gov (United States)

    Langston, Rosamund F; Wood, Emma R

    2010-10-01

    The hippocampus is thought to be required for the associative recognition of objects together with the spatial or temporal contexts in which they occur. However, recent data showing that rats with fornix lesions perform as well as controls in an object-place task, while being impaired on an object-place-context task (Eacott and Norman (2004) J Neurosci 24:1948-1953), suggest that not all forms of context-dependent associative recognition depend on the integrity of the hippocampus. To examine the role of the hippocampus in context-dependent recognition directly, the present study tested the effects of large, selective, bilateral hippocampus lesions in rats on performance of a series of spontaneous recognition memory tasks: object recognition, object-place recognition, object-context recognition and object-place-context recognition. Consistent with the effects of fornix lesions, animals with hippocampus lesions were impaired only on the object-place-context task. These data confirm that not all forms of context-dependent associative recognition are mediated by the hippocampus. Subsequent experiments suggested that the object-place task does not require an allocentric representation of space, which could account for the lack of impairment following hippocampus lesions. Importantly, as the object-place-context task has similar spatial requirements, the selective deficit in object-place-context recognition suggests that this task requires hippocampus-dependent neural processes distinct from those required for allocentric spatial memory, or for object memory, object-place memory or object-context memory. Two possibilities are that object, place, and context information converge only in the hippocampus, or that recognition of integrated object-place-context information requires a hippocampus-dependent mode of retrieval, such as recollection. © 2009 Wiley-Liss, Inc.

  12. Effect of diphenylthiocarbazone (dithizone) on glutamate level in hippocampus preparation in vitro and in vivo.

    Science.gov (United States)

    Kihara, T; Ishihara, T; Baba, A; Iwata, H

    1990-04-01

    To assess the functional interaction between Zn2+ and glutamate in hippocampus, diphenylthiocarbazone (dithizone), a Zn2+ chelator, was used to alter the glutamate level in hippocampus in vitro and in vivo. Dithizone at the concentration of 1 microM stimulated high K(+)- and veratrine-induced release of [3H]glutamate both in the presence and absence of Ca2+ from rat hippocampal slices preloaded with [3H]glutamate without affecting the release of [3H]gamma-aminobutyric acid and [3H]acetylcholine. Metal chelators other than dithizone did not evoke the [3H]glutamate release at the concentration of 10 microM. Two weeks after the intrahippocampal injection of 20 micrograms of dithizone, both Zn2+ and glutamate levels of the hippocampus significantly decreased with no change in the levels of other metals, amino acids, monoamines and acetylcholine.

  13. [Effect of high frequency electrotherapy on caspase-3 and ultra microstructure of hippocampus in rats following cerebral ischemia/reperfusion].

    Science.gov (United States)

    Fan, Yongmei; Wang, Rumi; Zhang, Changjie; Peng, Wenna; Yin, Jing; Hu, Zhiping

    2017-01-28

    To investigate the effect of high frequency electrotherapy (HFE) on rat hippocampus after cerebral ischemia/reperfusion (I/R).
 Methods: A rat model of cerebral I/R injury was established. The rats were randomly divided into a sham group, an I/R group and an HFE group. The HFE group received thearapy daily for different sessions for 1, 3, 7 d. Neuronal deficit score,neuron ultra microstructure in the hippocampus and caspase-3 protein expression were measured on 1 st, 3 th and 7th d.
 Results: Compared with the I/R group, the HFE group showed the decreased neurological deficit scores, with significant differences between the 2 groups (Pelectrotherapy can improve neural function, suppress caspase-3 expression and apoptosis in nerve cells and improve the ultra microstructure of neurons, displaying a protective effect on cerebral I/R injury in rats.

  14. Prevention of postoperative fatigue syndrome in rat model by ginsenoside Rb1 via down-regulation of inflammation along the NMDA receptor pathway in the hippocampus.

    Science.gov (United States)

    Chen, Wei-Zhe; Liu, Shu; Chen, Fan-Feng; Zhou, Chong-Jun; Yu, Jian; Zhuang, Cheng-Le; Shen, Xian; Chen, Bi-Cheng; Yu, Zhen

    2015-01-01

    Postoperative fatigue syndrome (POFS) is a common complication which decelerates recovery after surgery. The present study investigated the anti-fatigue effect of ginsenoside Rb1 (GRb1) through the inflammatory cytokine-mediated N-methyl-D-aspartate (NMDA) receptor pathway. A POFS rat model was created by major small intestinal resection and assessed with an open field test. Real-time quantitative polymerase chain reaction, western blot analysis, high performance liquid chromatography and a transmission electron microscopic analysis were used to determine typical biochemical parameters in the hippocampus. Our results showed that POFS rats exhibited fatigue associated with an increased expression of inflammatory cytokines and NMDA receptor 1, higher (kynurenine)/(tryptophan) and (kynurenine)/(kynurenic acid) on postoperative days 1 and 3, and an increased expression of indoleamine 2,3-dioxygenase (IDO) on postoperative day 1. Degenerated neurons were found in the hippocampus of POFS rats. The NMDA receptor antagonist MK801 had a significant effect on central fatigue on postoperative day 1. GRb1 had no effect on IDO or tryptophan metabolism, but exhibited a significant effect on POFS by inhibiting the expression of inflammatory cytokines and NMDA receptor 1. These data suggested that inflammatory cytokines could activate tryptophan metabolism to cause POFS through the NMDA receptor pathway. GRb1 had an anti-fatigue effect on POFS by reducing inflammatory cytokines and NMDA receptors.

  15. Effect of Banisteriopsis caapi and Psychotria viridis “ayahuasca Binomio” ingestion in the rat brain hippocampus

    OpenAIRE

    Castro, Américo; Químico Farmacéutico, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Ramos, Norma; Químico Farmacéutico, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Juárez, José; Químico Farmacéutico, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Inostroza, Luis; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Ponce, Juan; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Choquesillo, Fritz; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Félix, Luis; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Escudero, Jackeline; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Navarro, Arnaldo; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Huaman, Susan; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Machaca, Bryan; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; López, Julio; Médico Patólogo, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Ramirez, Emilio; Médico Patólogo, Escuela de Formación profesional, Farmacia y Bioquímica, Facultad de Ciencias Biológicas, Universidad Nacional San Cristóbal de Huamanga, Ayacucho, Perú; Ruiz, Julio; Médico Patólogo, Instituto de Investigación en Química Biológica, Microbiología y Biotecnología, Facultad de Farmacia y Bioquímica, UNMSM, Lima-Perú; Raez, José; Médico Patólogo, Instituto de Patología, Facultad de Medicina Humana, UNMSM, Lima-Perú

    2016-01-01

    Objective. To assess the effect of Banisteriopsis caapi and Psychotria viridis ‘binomio ayahuasca’ ingestion in rat hippocampus. Design. Experimental, descriptive, analytical, and cross-sectional study. Institution. Research Institute of Pharmaceutical Sciences and Natural Resources, Faculty of Pharmacy and Biochemistry, Universidad Nacional Mayor de San Marcos, Lima, Peru. Biological material. Rats. Interventions. Orogastric administration of ‘binomio ayahuasca’ in adult Rattus norvegicus al...

  16. Inhibition of indoleamine 2,3-dioxygenase 1/2 prevented cognitive impairment and energetic metabolism changes in the hippocampus of adult rats subjected to polymicrobial sepsis.

    Science.gov (United States)

    Comim, Clarissa M; Freiberger, Viviane; Ventura, Letícia; Mina, Francielle; Ferreira, Gabriela K; Michels, Monique; Generoso, Jaqueline S; Streck, Emílio L; Quevedo, João; Barichello, Tatiana; Dal-Pizzol, Felipe

    2017-04-15

    Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection that may affect the brain. We investigated the role of indoleamine 2,3-dioxygenase (IDO-1/2) inhibition on long-term memory and energetic metabolism after experimental sepsis by caecal ligation and perforation (CLP). Experimental sepsis increased the activity of complexes I, II-III and IV at 24h after CLP, and IDO-1/2 inhibition normalized the activity of these complexes in the hippocampus. Wistar rats presented impairment of habituation and aversive memories 10days after CLP. Adjuvant treatment with the IDO inhibitor prevented long-term cognitive impairment triggered by sepsis. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. [Effect of iodine deficiency and hypothyroidism on the protein expressions of CaMK II in the hippocampus of pups].

    Science.gov (United States)

    Wei, Wei; Dong, Jing; Liu, Wanyang; Wang, Yi; Chen, Jie

    2010-03-01

    To observe the effect of iodine deficiency and hypothyroidism on the protein expressions of CaMK II in the hippocampus of pups. Female Wistar rats (n=28) after pregnancy were randomly divided into control group, hypothyroid group and iodine deficient group. According to the dose of PTU in fed water, hypothyroid group was divided into 5 mg/L group and 15 mg/L group (7 in each). 5 pups from each group were sacrificed and perfused intracardially in PN7, PN14 and PN21. Brains were removed, fixed and sectioned coronally. All sections were observed and analyzed the protein exression of CaMK II by immunohistochemistry in the hippocampus CA1, CA3 and DG regions. Control group in CA1, CA3 and DG regions of the hippocampus had strong positive staining and the cytoplasm of neurons were filled with CaMK II. The distribution of the immune reaction product in hippocampus of 5 mg/L, 15 mg/L and iodine groups were in line with the control group, but the staining intensity as compared with the control group gradually decreased. In PN21 and PN14, integrated optical density average of CaMK II in CA1, CA3 and DG regions of the hippocampus in iodine deficient group [PN21: (26.05 +/- 4.98), (30.79 +/- 3.22), (26.40 +/- 2.63); PN14:(25.48 +/- 4.87), (44.17 +/- 5.91), (26.41 +/- 3.01)] and 15 mg/L groups [PN21: (17.02 +/- 2.68), (24.57 +/- 6.62), (20.18 +/- 4.05); PN14:(20.66 +/- 3.51), (34.94 +/- 5.09), (27.32 +/- 4.97)] were significantly lower than those of controls [PN21: (57.75 +/- 13.22), (65.03 +/- 6.20), (49.39 +/- 8.41), P CaMK II in CA1 region of the hippocampus in iodine deficient group (25.74 +/- 3.33) and 15 mg/L groups (26.89 +/- 5.25) were significantly lower than those of controls(40.53 +/- 3.65), P CaMK II.

  18. Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion hippocampus injury in rat brain.

    Science.gov (United States)

    Kapoor, Monika; Sharma, Neha; Sandhir, Rajat; Nehru, Bimla

    2017-10-28

    Blockage along with sudden restoration of blood following ischemia, results in several cascading events, such as a massive ROS production which plays an important role in the pathophysiology of ischemia. NADPH oxidase complex in mitochondria complex is believed to be the major source for ROS production. The present study explores the therapeutic potential of apocynin, an NADPH oxidase inhibitor in attenuating the ROS production, and the resultant neuroinflammation and mitochondrial injury during cerebral ischemia in rats. Bilateral common carotid artery occlusion (BCCAO) model was chosen for the study where intracellular ROS and NO levels as well as the NADPH oxidase activity were found to be increased significantly post 7th day of ischemic injury. Enhanced glial activation was observed and an upregulated expression of GFAP and Iba-1 in hippocampus along with that of the transcription factor NFκB and inflammatory markers iNOS, IL-1α, IL-1β and TNF-α.The activity of mitochondrial electron transport chain (ETC) complexes I, II, IV and V were significantly decreased following ischemia. Consequently, there was a decrease in mitochondrial membrane potential (MMP) while an increased release of cytochrome c and upregulated apoptotic markers Bax, caspase-3 and 9 initiated the programmed neuronal death which was also reflected by the marked increase in TUNEL positive cells in the hippocampal region. The physiological functional alterations have been observed following ischemic injury i.e memory and motor deficits. The apocynin supplementation significantly reduced the NADPH oxidase activity and resulted in declined ROS production which in-turn prevented the glial activation and downregulated the inflammatory and pro-apoptotic markers. Apocynin also restored the MMP (Δψm) and mitochondrial enzymes via inhibition of ROS vicious and relationship between NADPH oxidase and mitochondrial complexes. Apocynin treatment was also successfully reduced the behavioural deficits in

  19. Effect of 8 weeks Resistance Training on BDNF and TrkB in the Hippocampus of Adult Male Rats

    Directory of Open Access Journals (Sweden)

    S Mojtahedi

    2014-08-01

    Full Text Available Background & aim: Exercise enhances the synaptic plasticity and neuroprotective effects in the adult brain. However, it remains unknown that how plasticity molecules change following types of training. The purpose of this study was to determine the effect of eight weeks resistance training on protein levels of Brain Derived Neurotrophic Factor(BDNF and receptor of TrkB, in the hippocampus of adult male rats. Methods: In this experimental study, twelve adult male rats, 8 weeks of age, with an average weight of 200 to 225 grams were randomly divided into two groups, control and exercise respectively. The exercise was to increase the weight on the ladder. 24 hours after their last training session. The animals were killed and the hippocampus was removed for further testing. ELISA determined changes in protein levels. Data were analyzed by independent t test. Results: There was a significant difference between train and control groups In protein level of variables statically (p≤0.05. In addition, protein levels of BDNF and TrkB in the hippocampus of rats increased. Conclusion: Resistance training is beneficial for promoting hippocampal plasticity associated with BDNF signaling and consequently functional and cognitive benefits.

  20. Differential Effects of Cannabinoid Receptor Agonist on Social Discrimination and Contextual Fear in Amygdala and Hippocampus

    Science.gov (United States)

    Segev, Amir; Akirav, Irit

    2011-01-01

    We examined whether the cannabinoid receptor agonist WIN55,212-2 (WIN; 5 [mu]g/side) microinjected into the hippocampus or the amygdala would differentially affect memory processes in a neutral vs. an aversive task. In the aversive contextual fear task, WIN into the basolateral amygdala impaired fear acquisition/consolidation, but not retrieval.…

  1. [Possible mechanisms for orexin effects on the functioning of the hippocampus and spatial learning (analytical review)].

    Science.gov (United States)

    Sil'kis, I G

    2012-01-01

    We analyzed possible mechanisms for the influence of the "wakening hormone" orexin on spatial learning acting via changes in the functioning of the hippocampus and connected structures. The literature data point out that, firstly, orexin can directly potentiate excitation of neurons in different hippocampal areas by acting on Gq/11-protein-coupled postsynaptic OX1 and OX2 receptors. Due to facilitation of induction of the long-term potentiation of excitatory transmission at each stage of trisynaptic pathway through the hippocampus, orexin can promote transduction of information through this structure and formation of neural representations of object-place associations. Secondly, orexin can increase the release of acetylcholine, GABA and glutamate in the hippocampus by enhancing activity of neurons in the medial septum that have OX1 and OX2 receptors. This could lead to changes in intensity and frequency of the hippocampal theta rhythm. Thirdly, orexin can influence the functioning of reinforcing networks that include neurons of the hippocampus, prefrontal cortex, amygdala, ventral striatum, and ventral tegmental area by direct modulation of their activity through OX receptors. By enhancing the activity of dopaminergic neurons and increasing dopamine release, orexin can improve the functioning of reinforcing networks and facilitate spatial learning.

  2. Neurotropic effects of aspartame, stevia and sucralose on memory retention and on the histology of the hippocampus of the ICR mice(Mus musculus)

    National Research Council Canada - National Science Library

    Lejan Miguel Alabastro Villareal Rachelle Anne Montes Cruz Michael Bagui Ples Rodel Jonathan Santos Vitor

    2016-01-01

    ...: In this study, 20 mice were used to determine if there is an effect of consuming the maximum allowable dose of the non-nutritive sweeteners on the memory retention and on the histology of the hippocampus...

  3. Effects of acute voluntary loaded wheel running on BDNF expression in the rat hippocampus.

    Science.gov (United States)

    Lee, Minchul; Soya, Hideaki

    2017-12-31

    Voluntary loaded wheel running involves the use of a load during a voluntary running activity. A muscle-strength or power-type activity performed at a relatively high intensity and a short duration may cause fewer apparent metabolic adaptations but may still elicit muscle fiber hypertrophy. This study aimed to determine the effects of acute voluntary wheel running with an additional load on brain-derived neurotrophic factor (BDNF) expression in the rat hippocampus. Ten-week old male Wistar rats were assigned randomly to a (1) sedentary (Control) group; (2) voluntary exercise with no load (No-load) group; or (3) voluntary exercise with an additional load (Load) group for 1-week (acute period). The expression of BDNF genes was quantified by real-time PCR. The average distance levels were not significantly different in the No-load and Load groups. However, the average work levels significantly increased in the Load group. The relative soleus weights were greater in the No-load group. Furthermore, loaded wheel running up-regulated the BDNF mRNA level compared with that in the Control group. The BDNF mRNA levels showed a positive correlation with workload levels (r=0.75), suggesting that the availability of multiple workload levels contributes to the BDNF-related benefits of loaded wheel running noted in this study. This novel approach yielded the first set of findings showing that acute voluntary loaded wheel running, which causes muscular adaptation, enhanced BDNF expression, suggesting a possible role of high-intensity short-term exercise in hippocampal BDNF activity.

  4. Nicotinic receptors, memory, and hippocampus.

    Science.gov (United States)

    Kutlu, Munir Gunes; Gould, Thomas J

    2015-01-01

    Nicotinic acetylcholine receptors (nAChRs) modulate the neurobiological processes underlying hippocampal learning and memory. In addition, nicotine's ability to desensitize and upregulate certain nAChRs may alter hippocampus-dependent memory processes. Numerous studies have examined the effects of nicotine on hippocampus-dependent learning, as well as the roles of low- and high-affinity nAChRs in mediating nicotine's effects on hippocampus-dependent learning and memory. These studies suggested that while acute nicotine generally acts as a cognitive enhancer for hippocampus-dependent learning, withdrawal from chronic nicotine results in deficits in hippocampus-dependent memory. Furthermore, these studies demonstrated that low- and high-affinity nAChRs functionally differ in their involvement in nicotine's effects on hippocampus-dependent learning. In the present chapter, we reviewed studies using systemic or local injections of acute or chronic nicotine, nAChR subunit agonists or antagonists; genetically modified mice; and molecular biological techniques to characterize the effects of nicotine on hippocampus-dependent learning.

  5. The effects of Rhodiola rosea extract on 5-HT level, cell proliferation and quantity of neurons at cerebral hippocampus of depressive rats.

    Science.gov (United States)

    Chen, Q G; Zeng, Y S; Qu, Z Q; Tang, J Y; Qin, Y J; Chung, P; Wong, R; Hägg, U

    2009-09-01

    The purpose of this study was to investigate the effects of Rhodiola rosea extract and depression on the serotonin (5-HT) level, cell proliferation and quantity of neurons at cerebral hippocampus of depressive rats induced by Chronic Mild Stress (CMS). Seventy male Sprague-Dawley rats were divided into seven groups (10 per group): normal control group, untreated depressive rat model group, negative control group, positive control group, low dosage Rhodiola rosea extract (1.5g/kg) group, medium dosage Rhodiola rosea extract (3g/kg) group and high dosage Rhodiola rosea extract (6g/kg) group. After the depressive rats induced by CMS had received Rhodiola rosea extract for 3 weeks, the 5-HT levels at cerebral hippocampus were detected by high performance liquid chromatography. Bromodeoxyuridine (BrdU) was injected in vivo to label the proliferating cells at hippocampus, and morphometry was used to count the hippocampal neurons. The results showed that the 5-HT level of the three experimental groups had recovered to normal status. The immunohistochemistry of hippocampus BrdU positive cells had returned to the normal level in the group of depressive rats with low dosage Rhodiola rosea extract. In conclusion the results demonstrated that Rhodiola rosea extract could improve 5-HT level in hippocampus in depressive rats, and low dosage Rhodiola rosea could induce neural stem cell proliferation at hippocampus to return to normal level, repairing the injured neurons at hippocampus.

  6. [Effects of polydatin on learning and memory and Cdk5 kinase activity in the hippocampus of rats with chronic alcoholism].

    Science.gov (United States)

    Li, Xin-juan; Zhang, Yan; Xu, Chun-yang; Li, Shuang; Du, Ai-lin; Zhang, Li-bin; Zhang, Rui-ling

    2015-03-01

    To observe the effects of polydatin on learning and memory and cyclin-dependent kinase 5 (Cdk5) kinase activity in the hippocampus of rats with chronic alcoholism. Forty rats were randomly divided into 4 groups: control group, chronic alcoholism group, low and high polydatin group. The rat chronic alcoholism model was established by ethanol 3.0 g/(kg · d) (intragastric administration). The abstinence scoring was used to evaluate the rats withdrawal symptoms; cognitive function was measured by Morris water maze experiment; Cdk5 protein expression in the hippocampus was detected by immunofluorescence; Cdk5 kinase activity in the hippocampus was detected by liquid scintillation counting method. The abstinence score, escape latency, Cdk5 kinase activity in chronic alcoholism group rats were significantly higher than those of control group (P < 0.05). The abstinence score, escape latency in high polydatin group rats were significantly lower than those of chronic alcoholism group (P < 0.05); Cdk5 kinase activity in high and low polydatin group rats was significantly lower than that of chronic alcoholism group( P < 0.05); immunofluorescence showed that the Cdk5 positive cells of chronic alcoholism group were significantly increased compared with control group (P < 0.05), and the Cdk5 positive cells of polydatin groups were significantly decreased compared with chronic alcoholism group ( P < 0.05). Polydatin-reduced the chronic alcoholism damage may interrelate with regulation of Cdk5 kinase activity.

  7. The effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in hippocampus of STZ-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Abbasali Abbasnezhad

    2015-06-01

    Full Text Available Objective: Oxidative stress plays an important role in the etiology of diabetic complications. Diabetes impairs hippocampus neurogenesis, synaptic plasticity, and learning. The aim of this study was to investigate the effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in STZ-induced diabetic rats' hippocampus. Materials and Methods: Diabetes induced by 60 mg/kg STZ, i.p, and the rats were divided into five experimental groups (n=8-10 in each group including control (received 0.5 ml normal saline, untreated STZ-diabetic (received 0.5 ml normal saline, and treated rats received Nigella sativa extract (200 and 400 mg/kg or metformin (300 mg/kg by gavage for 42 days. Serum glucose concentration and body weight as well as hippocampus tissue malondialdehyde and thiollevels were determined by calorimetric assay. Results: Serum glucose level in the diabetic rats treated with 200 mg/kg Nigella sativaextract at the days 24 and 45 decreased in comparison to untreated diabetic group (p

  8. The Effect of Lorazepam and Aqueous Extract of Melissa officinalis on Histological Changes in the Hippocampus and Spatial Memory in Male Rats

    Directory of Open Access Journals (Sweden)

    Sakine Heydarifar

    2016-06-01

    Full Text Available Background and Objectives: Hippocampus is the most important part of learning and memory in the brain. Melissa officinalis naturally affects the nervous system and induces calmness. Lorazepam is also used in the treatment of insomnia and anxiety. In this study, the effect of Lorazepam and aqueous extract of Melissa officinalis (AEMO was investigated on hippocampus tissue and spatial memory in male rats using radial maze method. Methods: In this experimental study, 24 male Wistar rats were randomly divided into four groups. Control group received normal diet and water, the second group received lorazepam (dose. 10mg/kg, and two other groups received AEMO (at doses of 10 and 100mg/kg by gavage for 18 days. Then, their spatial memory were tested in an 8 arm radial maze (RAM. The level of lipid peroxidation of homogenized brain tissue was assessed, and hippocampal tissue sections were prepared and after H&E staining, DG area was investigated under a microscope. Data were analyzed using one-way ANOVA and Tukey statistical tests. The level of significance was set at p<0.05. Results: There was no significant difference in learning level between animals received lorazepam and control group. The results of the experiments showed the positive effect of low dose of AEMO (10mg/kg on spatial memory, while high dose of Melissa officinalis (100mg/kg prevented memory formation. Conclusion: The results of this research showed that AEMO can increase short-term memory at low dose (10mg/kg, but it may prevent spatial memory formation at high doses.

  9. Effect of Fluoxetine on the Hippocampus of Wistar Albino Rats in Cold Restraint Stress Model.

    Science.gov (United States)

    Jayakumar, Saikarthik; Raghunath, Gunapriya; Ilango, Saraswathi; Vijayakumar, J; Vijayaraghavan, R

    2017-06-01

    Stress has been known to be a potential modulator of learning and memory. Long term stress can lead to depression. Fluoxetine is a selective serotonin reuptake inhibitor group of drug used in the treatment of depression. The present study was conducted to evaluate the potential of Fluoxetine on cold restraint induced stress in the hippocampus of Wistar rats. A total of 18 male wistar albino rats were divided randomly into three groups (n=6). Group 1 was the control group which were kept in normal laboratory conditions. Group 2 was the negative control group which were given cold restraint stress for period of four weeks. Group 3 was the experimental group, where the animals were pretreated with fluoxetine 10 mg/kg for a period of one week followed by cold restraint stress for 30 minutes and cotreated with fluoxetine 10 mg/kg for a period of four weeks. The whole study was done for a period of five weeks followed by behavioural studies and subsequently sacrificed with removal of brain for various histological, Immunohistochemical (IHC), neurochemical and antioxidant analysis. The values were expressed as Mean±SEM. One-way analysis of variance followed by Tukey's multiple comparisons test was used for the comparison of means. A probability of 0.05 and less was taken as statistically significant using Prism Graphpad software version 6.01. The results show there was significant improvement in the Morris water maze test after treatment with fluoxetine in Group 2. Similar results were also noted in the levels of neurotransmitters and antioxidant levels in brain and also in the number of cells counted in IHC and histological studies by H&E when Group 3 was compared with Group 2. The treatment reversed the damage in Group 2 which was comparable with the control group. The results revealed that administration of fluoxetine 10 mg/kg given orally has a potential antistressor effect by improving the neurogenic and neuroprotective effect on the cold restraint stress induced

  10. The effect of silver nanoparticles on apoptosis and dark neuron production in rat hippocampus

    Directory of Open Access Journals (Sweden)

    Farzaneh Bagheri-abassi

    2015-07-01

    Full Text Available Objective(s:Silver nanoparticles (Ag-NPs are used widely in bedding, water purification, tooth paste and toys. These nanoparticles can enter into the body and move into the hippocampus. The aim of this study was to investigate the neurotoxicity of silver nanoparticles in the adult rat hippocampus. Materials and Methods:12 male Wistar rats were randomly divided into two experimental and control groups (6 rats in each group. Animals in the experimental group received Ag-NPs (30 mg/kg orally (gavage for 28 consecutive days. Control group in the same period was treated with distilled water via gavage. At the end of experiment, animals were deeply anesthetized, sacrificed, and their brains were collected from each group. Finally the brain sections were stained using toluidine blue and TUNEL. Then to compare the groups, dark neurons (DNs and apoptotic neurons were counted by morphometric method. Results: Results showed that the num­bers of DNs and apoptotic cells in the CA1, CA2, CA3, and dentate gyrus (DG of hippocampus significantly increased in the Ag-NPs group in comparison to the control group (P

  11. Adult Onset-hypothyroidism has Minimal Effects on Synaptic Transmission in the Hippocampus of Rats Independent of Hypothermia

    Science.gov (United States)

    Introduction: Thyroid hormones (TH) influence central nervous system (CNS) function during development and in adulthood. The hippocampus, a brain area critical for learning and memory is sensitive to TH insufficiency. Synaptic transmission in the hippocampus is impaired following...

  12. Effects of fluoxetine on the amygdala and the hippocampus after administration of a single prolonged stress to male Wistar rates: In vivo proton magnetic resonance spectroscopy findings.

    Science.gov (United States)

    Han, Fang; Xiao, Bing; Wen, Lili; Shi, Yuxiu

    2015-05-30

    Posttraumatic stress disorder (PTSD) is an anxiety- and memory-based disorder. The hippocampus and amygdala are key areas in mood regulation. Fluoxetine was found to improve the anxiety-related symptoms of PTSD patients. However, little work has directly examined the effects of fluoxetine on the hippocampus and the amygdala. In the present study, male Wistar rats received fluoxetine or vehicle after exposure to a single prolonged stress (SPS), an animal model of PTSD. In vivo proton magnetic resonance spectroscopy ((1)H-MRS) was performed -1, 1, 4, 7 and 14 days after SPS to examine the effects of fluoxetine on neurometabolite changes in amygdala, hippocampus and thalamus. SPS increased the N-acetylaspartate (NAA)/creatine (Cr) and choline moieties (Cho)/Cr ratios in the bilateral amygdala on day 4, decreased the NAA/Cr ratio in the left hippocampus on day 1, and increased both ratios in the right hippocampus on day 14. But no significant change was found in the thalamus. Fluoxetine treatment corrected the SPS increases in the NAA/Cr and Cho/Cr levels in the amygdala on day 4 and in the hippocampus on day 14, but it failed to normalise SPS-associated decreases in NAA/Cr levels in the left hippocampus on day 1. These results suggested that metabolic abnormalities in the amygdala and the hippocampus were involved in SPS, and different effects of fluoxetine in correcting SPS-induced neurometabolite changes among the three areas. These findings have implications for fluoxetine treatment in PTSD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Untangling elevation-related differences in the hippocampus in food-caching mountain chickadees: the effect of a uniform captive environment.

    Science.gov (United States)

    Freas, C A; Bingman, K; Ladage, L D; Pravosudov, V V

    2013-01-01

    significant effects on hippocampal neuron soma size. Overall our results showed that captivity has a strong effect on hippocampus volume, which could be due, at least partly, to a reduction in neuron soma size specifically in the hippocampus, but it did not override elevation-related differences in hippocampus volume or in the total number of hippocampal neurons. These data are consistent with the idea of the adaptive nature of the elevation-related differences associated with selection on spatial memory, while at the same time demonstrating additional environment-based plasticity in hippocampus volume, but not in neuron numbers. Our results, however, cannot rule out that the differences between elevations might still be driven by some developmental or early posthatching conditions/experiences. © 2013 S. Karger AG, Basel.

  14. Stress leads to contrasting effects on the levels of brain derived neurotrophic factor in the hippocampus and amygdala.

    Directory of Open Access Journals (Sweden)

    Harini Lakshminarasimhan

    Full Text Available Recent findings on stress induced structural plasticity in rodents have identified important differences between the hippocampus and amygdala. The same chronic immobilization stress (CIS, 2 h/day causes growth of dendrites and spines in the basolateral amygdala (BLA, but dendritic atrophy in hippocampal area CA3. CIS induced morphological changes also differ in their temporal longevity--BLA hypertrophy, unlike CA3 atrophy, persists even after 21 days of stress-free recovery. Furthermore, a single session of acute immobilization stress (AIS, 2 h leads to a significant increase in spine density 10 days, but not 1 day, later in the BLA. However, little is known about the molecular correlates of the differential effects of chronic and acute stress. Because BDNF is known to be a key regulator of dendritic architecture and spines, we investigated if the levels of BDNF expression reflect the divergent effects of stress on the hippocampus and amygdala. CIS reduces BDNF in area CA3, while it increases it in the BLA of male Wistar rats. CIS-induced increase in BDNF expression lasts for at least 21 days after the end of CIS in the BLA. But CIS-induced decrease in area CA3 BDNF levels, reverses to normal levels within the same period. Finally, BDNF is up regulated in the BLA 1 day after AIS and this increase persists even 10 days later. In contrast, AIS fails to elicit any significant change in area CA3 at either time points. Together, these findings demonstrate that both acute and chronic stress trigger opposite effects on BDNF levels in the BLA versus area CA3, and these divergent changes also follow distinct temporal profiles. These results point to a role for BDNF in stress-induced structural plasticity across both hippocampus and amygdala, two brain areas that have also been implicated in the cognitive and affective symptoms of stress-related psychiatric disorders.

  15. Differential effects of early life stress on hippocampus and amygdala volume as a function of emotional abilities.

    Science.gov (United States)

    Aust, Sabine; Stasch, Joanna; Jentschke, Sebastian; Alkan Härtwig, Elif; Koelsch, Stefan; Heuser, Isabella; Bajbouj, Malek

    2014-09-01

    Early life stress (ELS) is known to have considerable influence on brain development and affective functioning. Previous studies in clinical populations have shown that hippocampus and amygdala, two central structures of limbic emotion processing circuits, are predominantly affected by early stress exposure. Given the inconsistent findings on ELS-related effects in healthy populations and the associations of ELS and affective functioning, the question arises which additional emotion-relevant variables need to be considered to better understand the effects of ELS. We, therefore, investigated the volume of hippocampus and amygdala in 25 high alexithymic (h-ALEX) and 25 low alexithymic (l-ALEX) individuals, which were matched with regard to ELS, but significantly differed in their degree of emotional functioning. Volumetric analyses were performed using FSL-FIRST, a method to automatically segment subcortical structures on T1-weighted magnetic resonance images. Alexithymia was assessed using the Toronto Alexithymia Scale and Bermond-Vorst Alexithymia Questionnaire. ELS was assessed by Childhood Trauma Questionnaire (CTQ) and Early Trauma Inventory. Our data showed that ELS was negatively associated with right hippocampus volume in h-ALEX individuals, while there was no such association in the l-ALEX group. Furthermore, ELS was positively associated with left amygdala volume in l-ALEX individuals, but not in individuals with high levels of alexithymia. The present study emphasizes a substantial relationship between intrapersonal factors, such as alexithymia and neural alterations related to the experience of ELS. Longitudinal study designs are necessary to pursue the question of how emotional abilities interact with individual adaptations to early stress exposure on the neural level. © 2014 Wiley Periodicals, Inc.

  16. Effects of Chronic Alcohol Exposure on Kainate Receptor-Mediated Neurotransmission in the Hippocampus

    Science.gov (United States)

    2004-09-01

    Mexico REPORT NUMBER Albuquerque, New Mexico 87131-5041 E-Mail: fvalenzuela@ salud .unm. edu 9. SPONSORING /MONITORING 70. SPONSORING IMONITORING AGENCY...clusters. Schizophr and EPSP in area CAI of the rat hippocampus. J Physiol (Lond) 530: Bull 24: 267-283, 1998. 833-845, 1998. PENNARTZ CM, BOEUIrNOA PH ...glutamate Aldrich), 10mM HEPES, and 5 mM QX-314 ( pH adjusted with KOH; receptor is only now beginning to emerge and little is known 275-285 mOsM). Reagents

  17. Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

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    Cecilia Csölle

    Full Text Available Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7 results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/- displayed decreased immobility in the tail suspension test (TST and an attenuated anhedonia response in the sucrose preference test (SPT following bacterial endotoxin (LPS challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [(3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5. An increased 5-bromo-2-deoxyuridine (BrdU incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [(3H]5-HT and an elevated number of [(3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus.

  18. Protective effects of glucose-6-phosphate dehydrogenase on neurotoxicity of aluminium applied into the CA1 sector of rat hippocampus

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    Marina D Jovanovic

    2014-01-01

    Full Text Available Background & objectives: Aluminum (Al toxicity is closely linked to the pathogenesis of Alzheimer′s disease (AD. This experimental study was aimed to investigate the active avoidance behaviour of rats after intrahippocampal injection of Al, and biochemical and immunohistochemical changes in three bilateral brain structures namely, forebrain cortex (FBCx, hippocampus and basal forebrain (BF. Methods: Seven days after intra-hippocampal (CA1 sector injection of AlCl 3 into adult male Wistar rats they were subjected to two-way active avoidance (AA tests over five consecutive days. Control rats were treated with 0.9% w/v saline. The animals were decapitated on the day 12 post-injection. The activities of acetylcholinesterase (AChE and glucose-6-phosphate dehydrogenase (G6PDH were measured in the FBCx, hippocampus and BF. Immunohistochemical staining was performed for transferrin receptors, amyloid β and tau protein. Results: The activities of both AChE and G6PDH were found to be decreased bilaterally in the FBCx, hippocampus and basal forebrain compared to those of control rats. The number of correct AA responses was reduced by AlCl 3 treatment. G6PDH administered prior to AlCl 3 resulted in a reversal of the effects of AlCl 3 on both biochemical and behavioural parameters. Strong immunohistochemical staining of transferrin receptors was found bilaterally in the FBCx and the hippocampus in all three study groups. In addition, very strong amyloid β staining was detected bilaterally in all structures in AlCl 3 -treated rats but was moderate in G6PDH/AlCl 3 -treated rats. Strong tau staining was noted bilaterally in AlCl 3 -treated rats. In contrast, tau staining was only moderate in G6PDH/AlCl 3 -treated rats. Interpretation & conclusions: Our findings indicated that the G6PDH alleviated the signs of behavioural and biochemical effects of AlCl 3 -treatment suggesting its involvement in the pathogenesis of Al neurotoxicity and its potential

  19. Protective effects of glucose-6-phosphate dehydrogenase on neurotoxicity of aluminium applied into the CA1 sector of rat hippocampus

    Science.gov (United States)

    Jovanović, Marina D.; Jelenković, Ankica; Stevanović, Ivana D.; Bokonjić, Dubravko; Čolić, Miodrag; Petronijević, Nataša; Stanimirović, Danica B.

    2014-01-01

    Background & objectives: Aluminum (Al) toxicity is closely linked to the pathogenesis of Alzheimer's disease (AD). This experimental study was aimed to investigate the active avoidance behaviour of rats after intrahippocampal injection of Al, and biochemical and immunohistochemical changes in three bilateral brain structures namely, forebrain cortex (FBCx), hippocampus and basal forebrain (BF). Methods: Seven days after intra-hippocampal (CA1 sector) injection of AlCl3 into adult male Wistar rats they were subjected to two-way active avoidance (AA) tests over five consecutive days. Control rats were treated with 0.9% w/v saline. The animals were decapitated on the day 12 post-injection. The activities of acetylcholinesterase (AChE) and glucose-6-phosphate dehydrogenase (G6PDH) were measured in the FBCx, hippocampus and BF. Immunohistochemical staining was performed for transferrin receptors, amyloid β and tau protein. Results: The activities of both AChE and G6PDH were found to be decreased bilaterally in the FBCx, hippocampus and basal forebrain compared to those of control rats. The number of correct AA responses was reduced by AlCl3 treatment. G6PDH administered prior to AlCl3 resulted in a reversal of the effects of AlCl3 on both biochemical and behavioural parameters. Strong immunohistochemical staining of transferrin receptors was found bilaterally in the FBCx and the hippocampus in all three study groups. In addition, very strong amyloid β staining was detected bilaterally in all structures in AlCl3-treated rats but was moderate in G6PDH/AlCl3-treated rats. Strong tau staining was noted bilaterally in AlCl3-treated rats. In contrast, tau staining was only moderate in G6PDH/AlCl3-treated rats. Interpretation & conclusions: Our findings indicated that the G6PDH alleviated the signs of behavioural and biochemical effects of AlCl3-treatment suggesting its involvement in the pathogenesis of Al neurotoxicity and its potential therapeutic benefit. The present

  20. Effects of captivity and memory-based experiences on the hippocampus in mountain chickadees.

    Science.gov (United States)

    Ladage, Lara D; Roth, Timothy C; Fox, Rebecca A; Pravosudov, Vladimir V

    2009-04-01

    The complexity of an animal's physical environment is known to affect the hippocampus. Captivity may affect hippocampal anatomy and this may be attributable to the limited opportunities for memory-based experiences. This has tangential support, in that differential demands on memory can mediate changes in the hippocampus. What remains unclear is whether captivity directly affects hippocampal architecture and whether providing memory-based experiences in captivity can maintain hippocampal attributes comparable to wild-caught conspecifics. Using food-caching mountain chickadees (Poecile gambeli), we found that wild-caught individuals had larger hippocampal volumes relative to the rest of the telencephalon than captive birds with or without memory-based food-caching experiences, whereas there were no differences in neuron numbers or telencephalon volume. Also, there were no significant differences in relative hippocampal volume or neuron numbers between the captive birds with or without memory-based experiences. Our results demonstrate that captivity reduces hippocampal volume relative to the remainder of the telencephalon, but not at the expense of neuron numbers. Further, memory-based experiences in captivity may not be sufficient to maintain hippocampal volume comparable to wild-caught counterparts. (c) 2009 APA, all rights reserved.

  1. [Effects of electromagnetic radiation on RAF/MEK/ERK signaling pathway in rats hippocampus].

    Science.gov (United States)

    Zuo, Hong-yan; Wang, De-wen; Peng, Rui-yun; Wang, Shui-ming; Gao, Ya-bing; Xu, Xin-ping; Ma, Jun-Jie

    2009-05-01

    To study the development of changes for signaling molecules related to Raf/MEK/ERK pathway in hippocampus of rats after electromagnetic radiation, and investigate the mechanisms of radiation injury. Rats were exposed to X-HPM, S-HPM and EMP radiation source respectively, and animal model of electromagnetic radiation was established. Western blot was used to detect the expression of Raf-1, phosphorylated Raf-1 and phospholylated ERK. The expression of Raf-1 down-regulated during 6 h-14 d after radiation, most significantly at 7 d, and recovered at 28 d. There was no significant difference between the radiation groups. The expression of phosphorylated Raf-1 and phosphorylated ERK both up-regulated at 6 h and 7 d after radiation, more significantly at 6 h, and the two microwave groups were more serious for phosphorylated ERK. During 6 h-14 d after S-HPM radiation, the expression of phosphorylated Raf-1 increased continuously, but phosphorylated ERK changed wavily, 6 h and 7 d were expression peak. Raf/MEK/ERK signaling pathway participates in the hippocampus injury induced by electromagnetic radiation. The excessive activation of ERK pathway may result in the apoptosis and death of neurons, which is the important mechanism of recognition disfunction caused by electromagnetic radiation.

  2. Differential effects of duration and age upon the consequences of neuroinflammation in the hippocampus

    Science.gov (United States)

    Bardou, Isabelle; Brothers, Holly M.; Kaercher, Roxanne M.; Hopp, Sarah C.; Wenk, Gary L.

    2013-01-01

    The current study investigated the hypothesis that the duration of the pro-inflammatory environment plays a critical role in the brain’s response that result in negative consequences upon cognition, biochemistry and pathology. Lipopolysaccharide (LPS) or aCSF was slowly (250 ηg/hr) infused into the IVth ventricle of young (3 mo), adult (9 mo) or aged (23 mo) male F-344 rats for 21 or 56 days. The rats were then tested in the water pool task and endogenous hippocampal levels of pro- and anti-inflammatory proteins and genes as well as indicators of glutamatergic function were determined. The duration of the LPS infusion, as compared to the age of the rat, had the greatest impact upon 1) spatial working memory, 2) the density and distribution of activated microglia within the hippocampus, and 3) the cytokine protein and gene expression profiles within the hippocampus. The duration- and age-dependent consequences of neuroinflammation may explain why adult humans respond positively to anti-inflammatory therapies while aged humans do not. PMID:23639208

  3. Molecular determinants mediating effects of acute stress on hippocampus-dependent synaptic plasticity and learning.

    Science.gov (United States)

    Blank, Thomas; Nijholt, Ingrid; Spiess, Joachim

    2004-04-01

    The understanding of the molecular events underlying the neuroendocrine and behavioral sequelae of the response to stress has advanced rapidly over recent years. The hippocampus is a target of stress hormones, and we are beginning to dissect the molecular players in the modulation of synaptic plasticity and learning and memory involving this region of the brain. Given the wealth of data obtained from electrophysiological and behavioral experiments and in view of the importance to use identical experimental protocols in order to correlate the results obtained under both experimental conditions, this review focuses primarily on those contributions, which combine both approaches. From these studies it is evident that a single stressful event elicits responses in the hippocampus with different time-spans ranging from rapid changes in glutamatergic neurotransmission (i.e., N-methyl-d-aspartate receptor signaling), activation of second messenger cascades by corticotropin-releasing factor to long-lasting transcriptional changes of acetylcholinesterase. The relative contribution of these molecular targets to the stress response, the relation to hippocampal synaptic plasticity and memory formation, and the possible interaction of the underlying processes are discussed.

  4. Effect of environmental enrichment exposure on neuronal morphology of streptozotocin-induced diabetic and stressed rat hippocampus

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    Narendra Pamidi

    2014-08-01

    Full Text Available Background: Environmental enrichment (EE exposure is known to influence the structural changes in the neuronal network of hippocampus. In the present study, we evaluated the effects of EE exposure on the streptozotocin (STZ-induced diabetic and stressed rat hippocampus. Methods: Male albino rats of Wistar strain (4-5 weeks old were grouped into normal control (NC, vehicle control (VC, diabetes (DI, diabetes + stress (DI + S, diabetes + EE (DI + E, and diabetes + stress + EE (DI + S + E groups (n = 8 in each group. Rats were exposed to stress and EE after inducing diabetes with STZ (40 mg/kg. Rats were sacrificed on Day 30 and brain sections were processed for cresyl violet staining to quantify the number of surviving neurons in the CA1, CA3, and dentate hilus (DH regions of hippocampus. Results: A significant (p < 0.001 decrease in the number of survived neurons was noticed in DI (CA1, 34.06 ± 3.2; CA3, 36.1 ± 3.62; DH, 9.83 ± 2.02 as well as DI + S (CA1, 14.03 ± 3.12; CA3, 20.27 ± 4.09; DH, 6.4 ± 1.21 group rats compared to NC rats (CA1, 53.64 ± 2.96; CA3, 62.1 ± 3.34; DH, 21.11 ± 1.03. A significant (p < 0.001 increase in the number of survived neurons was observed in DI + E (CA1, 42.3 ± 3.66; CA3, 46.73 ± 4.74; DH, 17.03 ± 2.19 and DI + S + E (CA1, 29.69 ± 4.47; CA3, 36.73 ± 3.89; DH, 12.23 ± 2.36 group rats compared to DI and DI + S groups, respectively. Conclusions: EE exposure significantly reduced the amount of neuronal damage caused by complications of diabetes and stress to the neurons of hippocampus.

  5. Effect of chronic maternal ethanol administration on nitric oxide synthase activity in the hippocampus of the mature fetal guinea pig.

    Science.gov (United States)

    Kimura, K A; Parr, A M; Brien, J F

    1996-08-01

    Nitric oxide is a novel messenger that is involved in neuronal cell-cell communication and seems to play a neurotrophic role in normal brain development. Chronic prenatal ethanol exposure can produce central nervous system (CNS) teratogenesis, in which one of the target sites is the hippocampus. The main objective of our study was to test the following hypothesis: chronic maternal administration of an ethanol dosage regimen that produces CNS teratogenesis decreases nitric oxide synthase (NOS) activity in the fetal hippocampus. The ontogeny of NOS activity in the hippocampus of the developing guinea pig was further elucidated at two prenatal and two postnatal ages. The effects of chronic maternal oral administration of 4 g of ethanol/kg maternal body weight/day, isocaloric sucrose and pair feeding, or water [given as two equally divided doses 2 hr apart from gestational day (GD) 2 to GD 61] on body, brain, and hippocampal weights and hippocampal NOS activity were determined in the mature fetal guinea pig at GD 62 (term, about GD 68). NOS activity in the 25,000 x g supernatant fraction of hippocampal homogenate was measured using an optimized radiometric assay, based on the oxidation of L-[14C]arginine to L-[14C]citrulline. For the chronic ethanol regimen, the maternal blood ethanol concentration at 1 hr after the second divided dose on GD 57 was 157 +/- 45 mg/dl. Chronic maternal administration of ethanol decreased fetal body, brain, and hippocampal weights, compared with the isocaloric-sucrose/pair-fed and water treatment groups. The rate of L-[14C]citrulline formation and NOS activity in the fetal hippocampus were decreased in the ethanol treatment group, compared with the isocaloric-sucrose/ pair-fed and water treatment groups. There was no difference in the rate of L-[14C]citrulline formation, NOS activity, and fetal hippocampal and body weights between the isocaloric-sucrose/pair-fed and water treatment groups; however, fetal brain weight was decreased in the

  6. Effect of Alcohol and Tobacco Smoke on Long-Term Memory and Cell Proliferation in the Hippocampus of Rats.

    Science.gov (United States)

    Gomez, Rosane; Schneider, Ricardo; Quinteros, Dayane; Santos, Carolina Ferreira; Bandiera, Solange; Thiesen, Flavia Valadão; Coitinho, Adriana Simon; Fernandes, Marilda da Cruz; Wieczorek, Marina Godinho

    2015-12-01

    Alcohol is frequently used in combination with tobacco and few studies explore interactions between these two drugs of abuse. Here, we evaluated the effect of chronic alcohol administration and concomitant exposure to tobacco smoke on long-term memory and on cell proliferation in the hippocampus of rats. Forty male Wistar rats were assigned to four groups and treated with alcohol (2g/kg by gavage) and/or exposed to tobacco smoke (from six cigarettes, by inhalation) twice a day (at 9:00 AM and 2:00 PM) for 30 days. Long-term memory was evaluated in the inhibitory avoidance test and hippocampal cell proliferation was analyzed for bromodeoxyuridine immunohistochemistry. Our results showed that alcohol, tobacco smoke, or their combination improved the long-term memory evaluated by the memory index in rats. Moreover, alcohol and tobacco coadministration decreased bromodeoxyuridine-labeled cells by 60% when compared to the control group, while alcohol treatment decreased labeled cells by 40%. The tobacco group showed a nonsignificant 26% decrease in labeled cells compared to the control group. Chronic alcohol and tobacco coadministration improves the long-term memory in rats in the inhibitory avoidance test. However, coadministration decreases the cell proliferation in the hippocampus of rats, suggesting a deleterious effect by the combined use of these drugs of abuse. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Effects of sevoflurane on learning, memory, and expression of pERK1/2 in hippocampus in neonatal rats.

    Science.gov (United States)

    Yu, X; Liu, Y; Bo, S; Qinghua, L

    2015-01-01

    Sevoflurane may be associated with neural toxicity in the developing brain, but the mechanism is still unclear. Phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2) are important for developing neurons. The aim of our study was to investigate the effects of sevoflurane on spatial learning and memory and on expression of pERK1/2 in hippocampus of neonatal rats. Sixty-three neonatal rats were randomly divided into three groups: control group, sevoflurane (sevo) group, and sham group. Rats in the control group were placed in a plastic chamber flushed continuously for 4 h with air alone, rats in the sevo group were exposed in 5% sevoflurane and air for 4 h, and rats in the sham group were exposed in 5% carbon dioxide and air for 4 h, with identical flow rates for all groups. All three groups were subjected to Morris water maze test 1 day after sevoflurane exposure. Moreover, expression of pERK1/2 was determined by immunochemistry and Western blot at 1, 3, and 6 weeks after exposure. Compared with the control group, the escape latency was longer in sevo group and the expression of pERK1/2 was significantly inhibited in the sevo group (P learning and memory, and this may be attributed to decreased pERK1/2 in the hippocampus. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  8. Effects of long-term infusion of sedatives on the cognitive function and expression level of RAGE in hippocampus of rats.

    Science.gov (United States)

    Wang, Junyan; Niu, Mengxuan; Bai, Shuancheng

    2016-08-01

    This study aims to investigate the effects of long-term infusion of midazolam, propofol, and lytic cocktail on the rat cognitive ability and expression of receptor for advanced glycation end products (RAGE) in the hippocampus. The correlation between cognitive function and RAGE protein expression level could provide basis for clinical application. Adult male Wistar rats were first treated with midazolam, propofol, lytic cocktail, and saline solution for 5 consecutive days, respectively, and then their behavioral performance in a Morris water maze was monitored to determine the effects of these sedatives on the cognition of spatial learning and memory. After the behavioral tests, the expression level of RAGE protein in the hippocampus of each rat was determined by ELISA and immunohistochemistry. Compared with the control rats, the sedative-treated rats showed impaired performance in the Morris water maze. These three sedatives rendered similar extents of impairment of learning and memory at the first day after the treatment (p  0.05). In addition, midazolam and propofol, but not lytic cocktail, caused significant upregulation of RAGE expression in the hippocampus. The upregulation of RAGE protein was further corroborated by the increment of RAGE-positive cells in the CA1 region of hippocampus from midazolam- and propofol-treated rats. The long-term treatment of propofol, midazolam, and lytic cocktail could impair cognition. The upregulation of RAGE protein in hippocampus might play a role in the midazolam- and propofol-caused cognitive dysfunction.

  9. Effects of previous physical exercise to chronic stress on long-term aversive memory and oxidative stress in amygdala and hippocampus of rats.

    Science.gov (United States)

    Dos Santos, Tiago Marcon; Kolling, Janaína; Siebert, Cassiana; Biasibetti, Helena; Bertó, Carolina Gessinger; Grun, Lucas Kich; Dalmaz, Carla; Barbé-Tuana, Florencia María; Wyse, Angela T S

    2017-02-01

    Since stressful situations are considered risk factors for the development of depression and there are few studies evaluating prevention therapies for this disease, in the present study we evaluated the effect of previous physical exercise in animals subjected to chronic variable stress (CVS), an animal model of depression, on behavior tasks. We also investigated some parameters of oxidative stress and Na+, K+-ATPase activity, immunocontent and gene expression of alpha subunits in amygdala and hippocampus of rats. Young male rats were randomized into four study groups (control, exercised, stressed, exercised+stressed). The animals were subjected to controlled exercise treadmill for 20min,three times a week, for two months prior to submission to the CVS (40days). Results show that CVS impaired performance in inhibitory avoidance at 24h and 7days after training session. CVS induced oxidative stress, increasing reactive species, lipoperoxidation and protein damage, and decreasing the activity of antioxidant enzymes. The activity of Na+, K+-ATPase was decreased, but the immunocontents and gene expression of catalytic subunits were not altered. The previous physical exercise was able to improve performance in inhibitory avoidance at 24h after training; additionally, exercise prevented oxidative damage, but was unable to reverse completely the changes observed on the enzymatic activities. Our findings suggest that physical exercise during the developmental period may protect against aversive memory impairment and brain oxidative damage caused by chronic stress exposure later in life. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  10. Synaptophysin and the dopaminergic system in hippocampus are involved in the protective effect of rutin against trimethyltin-induced learning and memory impairment.

    Science.gov (United States)

    Zhang, Lei; Zhao, Qi; Chen, Chun-Hai; Qin, Qi-Zhong; Zhou, Zhou; Yu, Zheng-Ping

    2014-09-01

    This study aimed to investigate the protective effect of rutin against trimethyltin-induced spatial learning and memory impairment in mice. This study focused on the role of synaptophysin, growth-associated protein 43 and the action of the dopaminergic system in mechanisms associated with rutin protection and trimethyltin-induced spatial learning and memory impairment. Cognitive learning and memory was measured by Morris Water Maze. The expression of synaptophysin and growth-associated protein 43 in hippocampus was analyzed by western blot. The concentrations of dopamine, homovanillic acid, and dihyroxyphenylacetic acid in hippocampus were detected using reversed phase high-performance liquid chromatography with electrochemical detection. Trimethyltin-induced spatial learning impairment showed a dose-dependent mode. Synaptophysin but not growth-associated protein 43 was decreased in the hippocampus after trimethyltin administration. The concentration of dopamine decreased, while homovanillic acid increased in the hippocampus after trimethyltin administration. Mice pretreated with 20 mg/kg of rutin for 7 consecutive days exhibited improved water maze performance. Moreover, rutin pretreatment reversed the decrease of synaptophysin expression and dopamine alteration. These results suggest that rutin may protect against spatial memory impairment induced by trimethyltin. Synaptophysin and the dopaminergic system may be involved in trimethyltin-induced neuronal damage in hippocampus.

  11. Histological studies of neuroprotective effects of Curcuma longa Linn. on neuronal loss induced by dexamethasone treatment in the rat hippocampus.

    Science.gov (United States)

    Issuriya, Acharaporn; Kumarnsit, Ekkasit; Wattanapiromsakul, Chatchai; Vongvatcharanon, Uraporn

    2014-10-01

    Long term exposure to dexamethasone (Dx) is associated with brain damage especially in the hippocampus via the oxidative stress pathway. Previously, an ethanolic extract from Curcuma longa Linn. (CL) containing the curcumin constituent has been reported to produce antioxidant effects. However, its neuroprotective property on brain histology has remained unexplored. This study has examined the effects of a CL extract on the densities of cresyl violet positive neurons and glial fibrillary acidic protein immunoreactive (GFAP-ir) astrocytes in the hippocampus of Dx treated male rats. It showed that 21 days of Dx treatment (0.5mg/kg, i.p. once daily) significantly reduced the densities of cresyl violet positive neurons in the sub-areas CA1, CA3 and the dentate gyrus, but not in the CA2 area. However, CL pretreatment (100mg/kg, p.o.) was found to significantly restore neuronal densities in the CA1 and dentate gyrus. In addition, Dx treatment also significantly decreased the densities of the GFAP-ir astrocytes in the sub-areas CA1, CA3 and the dentate gyrus. However, CL pretreatment (100mg/kg, p.o.) failed to protect the loss of astrocytes in these sub-areas. These findings confirm the neuroprotective effects of the CL extract and indicate that the cause of astrocyte loss might be partially reduced by a non-oxidative mechanism. Moreover, the detection of neuronal and glial densities was suitable method to study brain damage and the effects of treatment. Copyright © 2014 Elsevier GmbH. All rights reserved.

  12. Caffeine Consumption Prevents Diabetes-Induced Memory Impairment and Synaptotoxicity in the Hippocampus of NONcZNO10/LTJ Mice: e21899

    National Research Council Canada - National Science Library

    João M N Duarte; Paula M Agostinho; Rui A Carvalho; Rodrigo A Cunha

    2012-01-01

    ... (a mixed antagonist of adenosine A1 and A2A receptors) emerges as a promising candidate since caffeine consumption reduces the risk of diabetes and effectively prevents memory deficits caused by different noxious stimuli...

  13. Differential proteomics analysis of the analgesic effect of electroacupuncture intervention in the hippocampus following neuropathic pain in rats

    Directory of Open Access Journals (Sweden)

    Gao Yong-Hui

    2012-12-01

    Full Text Available Abstract Background Evidence is building steadily on the effectiveness of acupuncture therapy in pain relief and repeated acupuncture-induced pain relief is accompanied by improvement of hippocampal neural synaptic plasticity. To further test the cellular and molecular changes underlying analgesic effect of acupuncture, the global change of acupuncture associated protein profiles in the hippocampus under neuropathic pain condition was profiled. Methods The chronic constrictive injury (CCI model was established by ligature of the unilateral sciatic nerve in adult Wistar rats. Rats were randomized into normal control (NC group, CCI group, and CCI with electroacupuncture (EA stimulation group. EA was applied to bilateral Zusanli (ST36 and Yanglingquan (GB34 in the EA group. Differentially expressed proteins in the hippocampus in the three groups were identified by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. The functional clustering of the identified proteins was analyzed by Mascot software. Results After CCI, the thermal pain threshold of the affected hind footpad was decreased and was reversed gradually by 12 sessions of acupuncture treatment. Following EA, there were 19 hippocampal proteins identified with significant changes in expression (>2-fold, which are involved in metabolic, physiological, and cellular processes. The top three canonical pathways identified were “cysteine metabolism”, “valine, leucine, and isoleucine degradation” and “mitogen-activated protein kinase (MAPK signaling”. Conclusions These data suggest that the analgesic effect of EA is mediated by regulation of hippocampal proteins related to amino acid metabolism and activation of the MAPK signaling pathway.

  14. Temporary inhibition of dorsal or ventral hippocampus by muscimol: distinct effects on measures of innate anxiety on the elevated plus maze, but similar disruption of contextual fear conditioning.

    Science.gov (United States)

    Zhang, Wei-Ning; Bast, Tobias; Xu, Yan; Feldon, Joram

    2014-04-01

    Studies in rats, involving hippocampal lesions and hippocampal drug infusions, have implicated the hippocampus in the modulation of anxiety-related behaviors and conditioned fear. The ventral hippocampus is considered to be more important for anxiety- and fear-related behaviors than the dorsal hippocampus. In the present study, we compared the role of dorsal and ventral hippocampus in innate anxiety and classical fear conditioning in Wistar rats, examining the effects of temporary pharmacological inhibition by the GABA-A agonist muscimol (0.5 ug/0.5 ul/side) in the elevated plus maze and on fear conditioning to a tone and the conditioning context. In the elevated plus maze, dorsal and ventral hippocampal muscimol caused distinct behavioral changes. The effects of ventral hippocampal muscimol were consistent with suppression of locomotion, possibly accompanied by anxiolytic effects, whereas the pattern of changes caused by dorsal hippocampal muscimol was consistent with anxiogenic effects. In contrast, dorsal and ventral hippocampal muscimol caused similar effects in the fear conditioning experiments, disrupting contextual, but not tone, fear conditioning. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Effect of ischemic preconditioning on the expression of c-myb in the CA1 region of the gerbil hippocampus after ischemia/reperfusion injury.

    Science.gov (United States)

    Lee, Hui Young; Tae, Hyun-Jin; Cho, Geum-Sil; Kim, In Hye; Cho, Jeong Hwi; Park, Joon Ha; Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Won, Moo-Ho; Park, Chan Woo; Cho, Jun Hwi; Seo, Jeong Yeol; Lee, Jae-Chul

    2016-06-01

    In the present study, we investigated the effect of ischemic preconditioning (IPC) on c-myb immunoreactivity as well as neuronal damage/death after a subsequent lethal transient ischemia in gerbils. IPC was subjected to a 2 min sublethal ischemia and a lethal transient ischemia was given 5 min transient ischemia. The animals in all of the groups were given recovery times of 1 day, 2 days and 5 days and we examined change in c-myb immunoreactivity as well as neuronal damage/death in the hippocampus induced by a lethal transient ischemia. A lethal transient ischemia induced a significant loss of cells in the stratum pyramidale (SP) of the hippocampal CA1 region at 5 days post-ischemia, and this insult showed that c-myb immunoreactivity in cells of the SP of the CA1 region was significantly decreased at 2 days post-ischemia and disappeared at 5 days post-ischemia. However, IPC effectively prevented the neuronal loss in the SP and showed that c-myb immunoreactivity was constitutively maintained in the SP after a lethal transient ischemia. Our results show that a lethal transient ischemia significantly decreased c-myb immunoreactivity in the SP of the CA1 region and that IPC well preserved c-myb immunoreactivity in the SP of the CA1 region. We suggest that the maintenance of c-myb might be related with IPC-mediated neuroprotection after a lethal ischemic insult.

  16. Effects of realgar on GSH synthesis in the mouse hippocampus: Involvement of system XAG(-), system XC(-), MRP-1 and Nrf2.

    Science.gov (United States)

    Wang, Yanlei; Chen, Mo; Zhang, Yinghua; Huo, Taoguang; Fang, Ying; Jiao, Xuexin; Yuan, Mingmei; Jiang, Hong

    2016-10-01

    Realgar is a type of mineral drug that contains arsenic and has neurotoxicity. Glutathione (GSH), which is the main antioxidant in the central nervous system, plays a key role in antioxidant defenses and the detoxification of arsenic. However, whether realgar interferes with the synthesis of GSH in the brain and the molecular mechanisms underlying its effects are largely unknown. Here, we used mouse models of exposure to realgar to show that realgar affects the synthesis of GSH in the hippocampus, leading to ultrastructural changes in hippocampal neurons and synapses and deficiencies in cognitive abilities, and that the mechanisms that cause this effect may be associated with alterations in the expression of system XAG(-), system XC(-), multidrug resistance-associated protein 1(MRP-1), nuclear factor E2-related factor 2 (Nrf2), γ-glutamylcysteine synthetase (γ-GCS), and the levels of glutamate (Glu) and cysteine (Cys) in the extracellular fluid. These findings provide a theoretical basis for preventing the drug-induced chronic arsenic poisoning in the nervous system that is triggered by realgar. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Effect of Paullinia cupana Mart. Commercial Extract During the Aging of Middle Age Wistar Rats: Differential Effects on the Hippocampus and Striatum.

    Science.gov (United States)

    Mingori, Moara Rodrigues; Heimfarth, Luana; Ferreira, Charles Francisco; Gomes, Henrique Mautone; Moresco, Karla Suzana; Delgado, Jeferson; Roncato, Sabrina; Zeidán-Chuliá, Fares; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2017-08-01

    During aging, there is a marked decline in the antioxidant capacity of brain tissue, leading to a gradual loss of the antioxidant/oxidant balance, which causes oxidative damage. The effects of Paullinia cupana Mart. extract, which is described as being rich in caffeine and many polyphenol compounds, on the central nervous system have not been extensively investigated. The aim of this study was to therefore investigate the effect of a commercial guarana extract (CGE) on cognitive function, oxidative stress, and brain homeostasis proteins related to cognitive injury and senescence in middle age, male Wistar rats. Animals were randomly assigned to a group according to their treatment (saline, CGE, or caffeine). Solutions were administered daily by oral gavage for 6 months. Open field and novel object recognition tasks were performed before and after treatment. Biochemical analyses were carried out on the hippocampus and striatum. Our open field data showed an increase in exploratory activity and a decrease in anxiety-like behavior with caffeine but not with the CGE treatment. In the CGE-treated group, catalase activity decreased in the hippocampus and increased in the striatum. Analyses of the hippocampus and striatum indicate that CGE and/or caffeine altered some of the analyzed parameters in a tissue-specific manner. Our data suggest that CGE intake does not improve cognitive development, but modifies the oxidative stress machinery and neurodegenerative-signaling pathway, inhibiting pro-survival pathway molecules in the hippocampus and striatum. This may contribute to the development of unfavorable microenvironments in the brain and neurodegenerative disorders.

  18. [Effect of Dipsacus total saponins on the ability of learning and memory and acetylcholine metabolism of hippocampus in AD rats].

    Science.gov (United States)

    Wan, Qiu-ying

    2015-01-01

    To study the effects of Dipsacus total saponins on the ability of learning and memory and its mechanism of action. Forty rats were randomly divided into blank control group, model group, Dipsacus group and positive control group (n = 10), general situation of rats were observed, the ability of learning and memory of rats was tested by Square water maze, the activities of acetylcholinesterase (AChE)and choline acetyltransferase (ChAT) of hippocampus in rats were measured using double antibody sandwich method. During the period of treatment, general situation had no obvious change in model group, but general situation and the ability of activity were gradually improved in Dipsacus group and positive control group. Compared with blank control group, the swimming time was obviously prolonged and the number of mistakes was obviously increased at different time, the activity of AChE was significantly enhanced and the activity of ChAT was significantly decreased in model group. Compared with model group, the swimming time was obviously shortened and the number of mistakes was obviously reduced at different time, the activities of AChE were significantly decreased and the activities of ChAT were significantly enhanced in Dipsacus group and positive control group; Compared with positive control group, the swimming time and the number of mistakes at different time and the activities of AChE and ChAT had no significant difference in Dipsacus group. Dipsacus total saponins can improve the ability of learning and memory in Alzheimer' s disease(AD) rats, its mechanism of 'action may be related to regulating ACh metabolism of hippocampus.

  19. AGONIST EFFECTS AT PUTATIVE CENTRAL 5-HT(4)RECEPTORS IN RAT HIPPOCAMPUS BY R(+)-ZACOPRIDE AND S(-)-ZACOPRIDE - NO EVIDENCE FOR STEREOSELECTIVITY

    NARCIS (Netherlands)

    BODDEKE, HWGM; KALKMAN, HO

    1992-01-01

    The EEG of halothane anaesthetized rats was recorded from an electrode implanted into the hippocampus. In the present study the effect of R(+)- and S()-zacopride, administered intra-cerebroventricularly, on different frequency bands of the EEG was investigated. Both enantiomers induced similar

  20. Agonist effects at putative central 5-HT4receptors in rat hippocampus by R(+)- and S(-)-zacopride; no evidence for stereo-selectivity

    NARCIS (Netherlands)

    Boddeke, H.W.G.M.; Kalkman, H.O.

    1992-01-01

    The EEG of halothane anaesthetized rats was recorded from an electrode implanted into the hippocampus. In the present study the effect of R(+)- and S(-)-zacopride, administered intra-cerebroventricularly, on different frequency bands of the EEG was investigated. Both enantiomers induced similar

  1. THE EFFECT OF THEOPHYLLINE AND IMMOBILIZATION STRESS ON HALOPERIDOL-INDUCED CATALEPSY AND ON METABOLISM IN THE STRIATUM AND HIPPOCAMPUS, STUDIED WITH LACTOGRAPHY

    NARCIS (Netherlands)

    DIJK, S; KRUGERS, HJ; KORF, J

    Whether inducing catalepsy in the rat by an intraperitoneal injection of haloperidol (0.5 mg/kg) had an effect on metabolism in the striatum and in the hippocampus, as determined by lactography, and whether reducing the cataleptic state with stress or theophylline (8 mg/kg i.v.) had any impact on

  2. Effects of combined acupuncture and eugenol on learning-memory ability and antioxidation system of hippocampus in Alzheimer disease rats via olfactory system stimulation.

    Science.gov (United States)

    Liu, Zhibin; Niu, Wenmin; Yang, Xiaohang; Wang, Yuan

    2013-06-01

    To investigate the effects of combined acupuncture and eugenol on learning-memory ability and the antioxidation system of the hippocampus in Alzheimer disease (AD) rats. Sixty Sprague Dawley rats, weighing (300 +/- 10) g, were randomly divided with 10 rats per group into a normal control group, AD model group, AD with cut olfactory nerve group, Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group. The AD model was established by injection of amyloid beta1-40 (Abeta 1-40). Morris maze tests were conducted for evaluating the learning-memory ability. Content of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus were detected. The average escape latency and the mean swimming distance in the normal control group, the Xiu three-needle group, the eugenol group, and the combined acupuncture and eugenol group were significantly shorter than those in the AD model group (all P 0.05). Compared with the normal control group, the MDA content in the hippocampus significantly increased (P 0.05). Both Xiu three-needle and eugenol can increase learning-memory ability, decrease MDA content, and increase SOD and GSH-Px activities in the hippocampus in AD rats. The combination of acupuncture with eugenol has stronger effects, and the effects depend on the olfactory pathway.

  3. Effects of eslicarbazepine acetate on acute and chronic latrunculin A-induced seizures and extracellular amino acid levels in the mouse hippocampus.

    Science.gov (United States)

    Sierra-Paredes, Germán; Loureiro, Ana I; Wright, Lyndon C; Sierra-Marcuño, Germán; Soares-da-Silva, Patrício

    2014-12-20

    Latrunculin A microperfusion of the hippocampus induces acute epileptic seizures and long-term biochemical changes leading to spontaneous seizures. This study tested the effect of eslicarbazepine acetate (ESL), a novel antiepileptic drug, on latrunculin A-induced acute and chronic seizures, and changes in brain amino acid extracellular levels. Hippocampi of Swiss mice were continuously perfused with a latrunculin A solution (4 μM, 1 μl/min, 7 h/day) with continuous EEG and videotape recording for 3 consecutive days. Microdialysate samples were analyzed by HPLC and fluorescence detection of taurine, glycine, aspartate, glutamate and GABA. Thereafter, mice were continuously video monitored for two months to identify chronic spontaneous seizures or behavioral changes. Control EEG recordings (8 h) were performed in all animals at least once a week for a minimum of one month. Oral administration of ESL (100 mg/kg), previous to latrunculin A microperfusion, completely prevented acute latrunculin A-induced seizures as well as chronic seizures and all EEG chronic signs of paroxysmal activity. Hippocampal extracellular levels of taurine, glycine and aspartate were significantly increased during latrunculin A microperfusion, while GABA and glutamate levels remained unchanged. ESL reversed the increases in extracellular taurine, glycine and aspartate concentrations to basal levels and significantly reduced glutamate levels. Plasma and brain bioanalysis showed that ESL was completely metabolized within 1 h after administration to mainly eslicarbazepine, its major active metabolite. ESL treatment prevented acute latrunculin A-induced seizures as well as chronic seizures and all EEG chronic signs of paroxysmal activity, supporting a possible anti-epileptogenic effect of ESL in mice.

  4. Effects of visual deprivation during brain development on expression of AMPA receptor subunits in rat’s hippocampus

    Directory of Open Access Journals (Sweden)

    Sayyed Alireza Talaei

    2015-06-01

    Conclusion: Dark rearing of rats during critical period of brain development changes the relative expression and also arrangement of both AMPA receptor subunits, GluR1 and GluR2 in the hippocampus, age dependently.

  5. Effects of Short-Term Exposure to Lithium on Antiapoptotic Bcl-xL Protein Expression in Cortex and Hippocampus of Rats after Acute Stress.

    Science.gov (United States)

    Dygalo, N N; Bannova, A V; Sukhareva, E V; Shishkina, G T; Ayriyants, K A; Kalinina, T S

    2017-03-01

    The antiapoptotic protein Bcl-xL is involved in development of neurobiological resilience to stress; hence, the possibility of use of psychotropic drugs to increase its expression in brain in response to stress is of considerable interest. Lithium is a neurotropic drug widely used in psychiatry. In work, we studied effects of lithium administration (for 2 or 7 days) on the expression of Bcl-xL mRNA and protein in the hippocampi and cortices of rats subjected to stress that induced depression-like behavior in the animals. In contrast to the brain-derived neurotrophic factor (BDNF), whose expression decreased in the hippocampus in response to acute stress, stress increased the level of Bcl-xL mRNA in the hippocampus, but decreased it in the frontal cortex. Treatment of stressed animals with lithium for 2 or 7 days increased Bcl-xL protein levels 1.5-fold in the hippocampus, but it decreased them in the cortex. Therefore, Bcl-xL expression in the brain can be modulated by both stress and psychotropic drugs, and the effects of these factors are brain region-specific: both stress exposure and lithium administration activated Bcl-xL expression in the hippocampus and suppressed it in the frontal cortex. The activation of Bcl-xL expression in the hippocampus by lithium, demonstrated for the first time in this study, suggests an important role of this protein in the therapeutic effects of lithium in the treatment of stress-induced psychoemotional disorders.

  6. Proteomic Analysis of the Effect of Acupuncture on the Suppression of Kainic Acid-Induced Neuronal Destruction in Mouse Hippocampus

    OpenAIRE

    Bae, Chang-Hwan; Kim, Dong-Soo; Jun, Ye Lee; Kwon, Sunoh; Park, Hi-Joon; Hahm, Dae-Hyun; Lee, Hyejung; Kim, Seung-Tae

    2013-01-01

    Kainic acid (KA) is a neurotoxin that induces epileptic seizures and excitotoxicity in the hippocampus. Acupuncture is frequently used as an alternative therapy for epilepsy, and it has been known to protect hippocampal neurons against KA toxicity. Using proteomic analysis, we investigated protein expression changes in the hippocampus following acupuncture stimulation at HT8. Eight-week-old male C57BL/6 mice (20–25 g) received acupuncture treatment at HT8 acupoint bilaterally once a day for 3...

  7. Proteomic analysis of the effect of acupuncture on the suppression of kainic Acid-induced neuronal destruction in mouse hippocampus.

    Science.gov (United States)

    Bae, Chang-Hwan; Kim, Dong-Soo; Jun, Ye Lee; Kwon, Sunoh; Park, Hi-Joon; Hahm, Dae-Hyun; Lee, Hyejung; Kim, Seung-Tae

    2013-01-01

    Kainic acid (KA) is a neurotoxin that induces epileptic seizures and excitotoxicity in the hippocampus. Acupuncture is frequently used as an alternative therapy for epilepsy, and it has been known to protect hippocampal neurons against KA toxicity. Using proteomic analysis, we investigated protein expression changes in the hippocampus following acupuncture stimulation at HT8. Eight-week-old male C57BL/6 mice (20-25 g) received acupuncture treatment at HT8 acupoint bilaterally once a day for 3 days and were then administered KA (30 mg/kg) intraperitoneally. Twenty-four hours after KA injection, neuronal survival and astrocyte activation in the hippocampus were measured, and protein expression in the hippocampus was identified by 2-dimensional electrophoresis. Acupuncture stimulation at HT8 suppressed KA-induced neuronal death and astrocyte activation in the hippocampus. We identified the changes in the expression of 11 proteins by KA or acupuncture stimulation at HT8 and found that acupuncture stimulation at HT8 normalized the expression of dihydropyrimidinase-related protein 2 and upregulated the expression of transcriptional activator protein pur-alpha, serine/threonine-protein phosphatase 5, and T-complex protein 1 subunit alpha, which are related to the survival of neurons. These results suggest that acupuncture stimulation at HT8 changes protein expression profiles in the hippocampus in favor of neuronal survival in KA-treated mice.

  8. Proteomic Analysis of the Effect of Acupuncture on the Suppression of Kainic Acid-Induced Neuronal Destruction in Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Chang-Hwan Bae

    2013-01-01

    Full Text Available Kainic acid (KA is a neurotoxin that induces epileptic seizures and excitotoxicity in the hippocampus. Acupuncture is frequently used as an alternative therapy for epilepsy, and it has been known to protect hippocampal neurons against KA toxicity. Using proteomic analysis, we investigated protein expression changes in the hippocampus following acupuncture stimulation at HT8. Eight-week-old male C57BL/6 mice (20–25 g received acupuncture treatment at HT8 acupoint bilaterally once a day for 3 days and were then administered KA (30 mg/kg intraperitoneally. Twenty-four hours after KA injection, neuronal survival and astrocyte activation in the hippocampus were measured, and protein expression in the hippocampus was identified by 2-dimensional electrophoresis. Acupuncture stimulation at HT8 suppressed KA-induced neuronal death and astrocyte activation in the hippocampus. We identified the changes in the expression of 11 proteins by KA or acupuncture stimulation at HT8 and found that acupuncture stimulation at HT8 normalized the expression of dihydropyrimidinase-related protein 2 and upregulated the expression of transcriptional activator protein pur-alpha, serine/threonine-protein phosphatase 5, and T-complex protein 1 subunit alpha, which are related to the survival of neurons. These results suggest that acupuncture stimulation at HT8 changes protein expression profiles in the hippocampus in favor of neuronal survival in KA-treated mice.

  9. [Effects of Tianbingtiaodu capsule on improvement of learning and memory abilities and expression of NMDAR1 of epileptic rats in the hippocampus].

    Science.gov (United States)

    Wang, Yu; Pei, Lin; Liu, Chun-Yan; Pei, Yi-Ran; Jia, Xiao-Ming

    2010-06-01

    To study effects of Tianbingtiaodu capsule on changement of learning and memory abilities and expression of NMDAR1 in epileptic rats. Picrotoxin (1.5 mg/kg) was injected intraperitonrally in SD rats for thirty days. After the repeated attacks epilepsy model had been established successfully, model rats were randomly divided into model group, Tianbingtiaodu capsule low dosage (0.4 g/kg) group, Tianbingtiaodu capsules high dosage(0. 8 g/kg) group, Piracetam group and Piracetam and Valproate group. All groups were fed everyday. Sixty days later, the learning and memory abilities were tested with Morris water maze method. Expression of NMDAR1 in hippocampus was observed with western-blot and immunohistochemical method. The expression of NMDAR1 mRNA in hippocampus was determined by RT-PCR. Compared to the control group, the learning and memory abilities were significantly lower (P hippocampus AC3 significantly increased in model group (P learning and memory abilities and expression of NMDAR1 in hippocampus was improved significantly in Tianbingtiaodu group (P learning and memory in rats after repeated attacks of epilepsy through adjusting the NMDAR1 expression.

  10. Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats

    Science.gov (United States)

    Baquedano, Eva; García-Cáceres, Cristina; Diz-Chaves, Yolanda; Lagunas, Natalia; Calmarza-Font, Isabel; Azcoitia, Iñigo; Garcia-Segura, Luis M.; Argente, Jesús; Chowen, Julie A.; Frago, Laura M.

    2011-01-01

    Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID:22096592

  11. Effects of arsenic exposure from drinking water on spatial memory, ultra-structures and NMDAR gene expression of hippocampus in rats.

    Science.gov (United States)

    Luo, Jiao-hua; Qiu, Zhi-qun; Shu, Wei-qun; Zhang, Yong-yan; Zhang, Liang; Chen, Ji-an

    2009-01-30

    Epidemiological investigations indicate that chronic arsenic exposure can damage neurobehavioral function in children. The present study was aimed to study the effects of arsenic exposure from drinking water on the spatial memory, and hippocampal ultra-structures and N-methyl-d-aspartate receptor (NMDAR) gene expression in rats. Sprague-Dawley rats were assigned to four groups: rats in control group drank regular water, rats in other groups drank water with final arsenic concentration of 2.72 mg/L (group A), 13.6 mg/L (group B) and 68 mg/L (group C), respectively, for 3 months. The levels of arsenic in blood serum and hippocampus were monitored. Rats were tested in Morris water maze (MWM) for memory status. Samples of hippocampus were collected from two rats in each group for transmission electron microscopic study and the detection of NMDAR expression by RT-PCR. The rats in group C showed a significant delay in hidden platform acquisition. Neurons and endothelial cells presented pathological changes and the expression of NR2A was down-regulated in hippocampus in arsenic exposed rats. Our data indicated that arsenic exposure of 68 mg/L caused spatial memory damage, of which the morphological and biochemical bases could be the ultra-structure changes and reduced NR2A expression in hippocampus.

  12. The hippocampus and dorsal raphe nucleus are key brain areas associated with the antidepressant effects of lithium augmentation of desipramine.

    Science.gov (United States)

    Cussotto, Sofia; Cryan, John F; O'Leary, Olivia F

    2017-05-01

    Approximately 50% of depressed individuals fail to achieve remission with first-line antidepressant drugs and a third remain treatment-resistant. When first-line antidepressant treatment is unsuccessful, second-line strategies include dose optimisation, switching to another antidepressant, combination with another antidepressant, or augmentation with a non-antidepressant medication. Much of the evidence for the efficacy of augmentation strategies comes from studies using lithium to augment the effects of tricyclic antidepressants. The neural circuitry underlying the therapeutic effects of lithium augmentation is not yet fully understood. Recently, we reported that chronic treatment with a combination of lithium and the antidepressant desipramine, exerted antidepressant-like behavioural effects in a mouse strain (BALB/cOLaHsd) that did not exhibit an antidepressant-like behavioural response to either drug alone. In the present study, we used this model in combination with ΔFosB/FosB immunohistochemistry to identify brain regions chronically affected by lithium augmentation of desipramine when compared to either treatment alone. The data suggest that the dorsal raphe nucleus and the CA3 regions of the dorsal hippocampus are key nodes in the neural circuitry underlying antidepressant action of lithium augmentation of desipramine. These data give new insight into the neurobiology underlying the mechanism of lithium augmentation in the context of treatment-resistant depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Recognition memory for social and non-social odors: differential effects of neurotoxic lesions to the hippocampus and perirhinal cortex.

    Science.gov (United States)

    Feinberg, Leila M; Allen, Timothy A; Ly, Denise; Fortin, Norbert J

    2012-01-01

    The contributions of the hippocampus (HC) and perirhinal cortex (PER) to recognition memory are currently topics of debate in neuroscience. Here we used a rapidly-learned (seconds) spontaneous novel odor recognition paradigm to assess the effects of pre-training N-methyl-D-aspartate lesions to the HC or PER on odor recognition memory. We tested memory for both social and non-social odor stimuli. Social odors were acquired from conspecifics, while non-social odors were household spices. Conspecific odor stimuli are ethologically-relevant and have a high degree of overlapping features compared to non-social household spices. Various retention intervals (5 min, 20 min, 1h, 24h, or 48 h) were used between study and test phases, each with a unique odor pair, to assess changes in novelty preference over time. Consistent with findings in other paradigms, modalities, and species, we found that HC lesions yielded no significant recognition memory deficits. In contrast, PER lesions caused significant deficits for social odor recognition memory at long retention intervals, demonstrating a critical role for PER in long-term memory for social odors. PER lesions had no effect on memory for non-social odors. The results are consistent with a general role for PER in long-term recognition memory for stimuli that have a high degree of overlapping features, which must be distinguished by conjunctive representations. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. [Effect of electroacupuncture on epileptic EEG and intracellular Ca2+ content in the hippocampus in epilepsy rats].

    Science.gov (United States)

    Yang, Fan; Xu, Guo-long; Yang, Yong-qing; Shen, De-kai; Feng, Pin-zhi; Wang, Pin; Liu, Xiang-guo

    2009-06-01

    To study the underlying mechanism of electroacupuncture (EA) in relieving epilepsy in pentylenetetrazole (PTZ)-induced epilepsy rats. Twenty SD rats were randomly divided into normal control, model, EA, Nimodipine groups, with 5 cases in each. Epilepsy model was established by intraperitoneal injection of PTZ (32.0 mg/kg), once daily for 28 days. EA (100 Hz, 0.6 mA) was applied to "Baihui" (GV 20) and "Dazhui" (GV 14), once daily for 7 days. For Nimodipine group, the rats were given with nimodipine (0.25 mg/kg, i.p.), once daily for 7 days. Electroencephalogram (EEG) was recorded and the fluorescence intensity of Ca2+ of the hippocampus tissue sections was detected by laser scanning confocal microscope (LSCM) after incubation in artificial cerebrospinal fluid containing Flou-3/AM (10 micromol/L) and pluronic F-127 (5 microl). Compared with model group, the latencies of epileptic EEG seizure prolonged obviously (P 0.05). EA has an obvious anti-epileptic effect, which may be closely related to its effect in downregulating the increased hippocampal Ca2+ level in PTZ-kindled epilepsy rats.

  15. Effects of hippocampal state-contingent trial presentation on hippocampus-dependent nonspatial classical conditioning and extinction.

    Science.gov (United States)

    Nokia, Miriam S; Wikgren, Jan

    2014-04-23

    Hippocampal local field potentials are characterized by two mutually exclusive states: one characterized by regular θ oscillations (∼4-8 Hz) and the other by irregular sharp-wave ripples. Presenting stimuli during dominant θ oscillations leads to expedited learning, suggesting that θ indexes a state in which encoding is most effective. However, ripple-contingent training also expedites learning, suggesting that any discrete brain state, much like the external context, can affect learning. We trained adult rabbits in trace eyeblink conditioning, a hippocampus-dependent nonspatial task, followed by extinction. Trials were delivered either in the presence or absence of θ or regardless of hippocampal state. Conditioning in the absence of θ led to more animals learning, although learning was slower compared with a yoked control group. Contrary to expectations, conditioning in the presence of θ did not affect learning. However, extinction was expedited both when it was conducted contingent on θ and when it was conducted in a state contrary to that used to trigger trials during conditioning. Strong phase-locking of hippocampal θ-band responses to the conditioned stimulus early on during conditioning predicted good learning. No such connection was observed during extinction. Our results suggest that any consistent hippocampal oscillatory state can potentially be used to regulate learning. However, the effects depend on the specific state and task at hand. Finally, much like the external environment, the ongoing neural state appears to act as a context for learning and memory retrieval.

  16. Adverse effect of the combination of hypothyroidism and chronic psychosocial stress on hippocampus-dependent memory in rats.

    Science.gov (United States)

    Gerges, Nashaat Z; Alzoubi, Karem H; Park, Collin R; Diamond, David M; Alkadhi, Karim A

    2004-11-05

    Both hypothyroidism and stress interfere with cognitive function in patients. This study examined the effect of hypothyroidism and stress on hippocampus-dependent learning and memory in rats using the novel radial arm water maze (RAWM), which measures spatial working memory. Hypothyroidism was accomplished by thyroidectomy and 2 weeks later a form of intruder stress was used as the chronic psychosocial stressor. After 4-6 weeks of stress, rats were trained to learn (during the acquisition phase; four trials) and then remember (during two memory test trials occurring 15 and 120 min after the acquisition phase) the within-day location of a hidden escape platform, which was in different arm every day. The number of errors (entry into arms other than the platform arm) was noted. Within-day learning of the platform location was largely unaffected by the experimental manipulations, indicating that rats in all groups were equally capable of finding the platform to escape from the water with similar numbers of errors (P > 0.005). The number of days a rat took to reach a criterion (DTC; a maximum of one error in three consecutive days) indicated that chronic stress or hypothyroidism, alone, resulted in a mild impairment of spatial memory, and the combination of chronic stress and hypothyroidism resulted in a more severe and long-lasting memory impairment. The data indicated that the combination of stress and hypothyroidism produced more deleterious effects on hippocampal function than either chronic stress or hypothyroidism alone.

  17. Disparate Effects of Lithium and a GSK-3 Inhibitor on Neuronal Oscillatory Activity in Prefrontal Cortex and Hippocampus

    Directory of Open Access Journals (Sweden)

    Tuan Nguyen

    2018-01-01

    Full Text Available Glycogen synthase kinase-3 (GSK-3 plays a critical role in cognitive dysfunction associated with Alzheimer’s disease (AD, yet the mechanism by which GSK-3 alters cognitive processes in other disorders, such as schizophrenia, remains unknown. In the present study, we demonstrated a role for GSK-3 in the direct regulation of neuronal oscillations in hippocampus (HIP and prelimbic cortex (PL. A comparison of the GSK-3 inhibitors SB 216763 and lithium demonstrated disparate effects of the drugs on spatial memory and neural oscillatory activity in HIP and PL. SB 216763 administration improved spatial memory whereas lithium treatment had no effect. Analysis of neuronal local field potentials in anesthetized animals revealed that whereas both repeated SB 216763 (2.5 mg/kg and lithium (100 mg/kg induced a theta frequency spike in HIP at approximately 10 Hz, only SB 216763 treatment induced an overall increase in theta power (4–12 Hz compared to vehicle. Acute administration of either drug suppressed slow (32–59 Hz and fast (61–100 Hz gamma power. In PL, both drugs induced an increase in theta power. Repeated SB 216763 increased HIP–PL coherence across all frequencies except delta, whereas lithium selectively suppressed delta coherence. These findings demonstrate that GSK-3 plays a direct role in the regulation of theta oscillations in regions critically involved in cognition, and highlight a potential mechanism by which GSK-3 may contribute to cognitive decline in disorders of cognitive dysfunction.

  18. Antinociceptive Effect of Morphine Microinjections into the Dorsal Hippocampus in the Formalin-Induced Orofacial Pain in Rats

    Directory of Open Access Journals (Sweden)

    Emad Khalilzadeh

    2010-09-01

    Full Text Available In the present study, the effects of intra-hippocampal microinjections of morphine (an opioid agonist and naloxone (an opioid antagonist were investigated in the formalin-induced orofacial pain in rats. Orofacial pain was induced by subcutaneous injection of formalin (1 %, 50 μl in the upper lip region and the time spent of face rubbing was measured in 3-min blocks for 45 min. Formalin induced a biphasic (first phase: 0-3 min; second phase: 15-33 min pain response. Intra-hippocampal microinjections of morphine at doses of 2 and 4 μg significantly (P < 0.05 attenuated the first phase, and at doses of 1, 2 and 4 μg, morphine significantly (P < 0.05 suppressed both phases of formalin-induced orofacial pain response. Intra-hippocampal microinjections of naloxone (1 and 4 μg non-significantly increased pain when used alone, and in pretreatment microinjection, naloxone (4 μg reversed morphine (2 μg-induced antinociception. These results indicate that at the level of hippocampus of the brain, morphine through a naloxone-reversible mechanism produced an antinociceptive effect confronting the pain induced by formalin in the orofacial region in rats.

  19. Comparative effects of parathion and chlorpyrifos on extracellular endocannabinoid levels in rat hippocampus: Influence on cholinergic toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jing [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States); Parsons, Loren [Committee on Neurobiology of Affective Disorders, The Scripps Research Institute, La Jolla, CA (United States); Pope, Carey, E-mail: carey.pope@okstate.edu [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States)

    2013-11-01

    Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). Endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) can modulate neurotransmission by inhibiting neurotransmitter release. We proposed that differential inhibition of eCB-degrading enzymes (fatty acid amide hydrolase, FAAH, and monoacylglycerol lipase, MAGL) by PS and CPF leads to differences in extracellular eCB levels and toxicity. Microdialysis cannulae were implanted into hippocampus of adult male rats followed by treatment with vehicle (peanut oil, 2 ml/kg, sc), PS (27 mg/kg) or CPF (280 mg/kg) 6–7 days later. Signs of toxicity, AChE, FAAH and MAGL inhibition, and extracellular levels of AEA and 2AG were measured 2 and 4 days later. Signs were noted in PS-treated rats but not in controls or CPF-treated rats. Cholinesterase inhibition was extensive in hippocampus with PS (89–90%) and CPF (78–83%) exposure. FAAH activity was also markedly reduced (88–91%) by both OPs at both time-points. MAGL was inhibited by both OPs but to a lesser degree (35–50%). Increases in extracellular AEA levels were noted after either PS (about 2-fold) or CPF (about 3-fold) while lesser treatment-related 2-AG changes were noted. The cannabinoid CB1 receptor antagonist/inverse agonist AM251 (3 mg/kg, ip) had no influence on functional signs after CPF but markedly decreased toxicity in PS-treated rats. The results suggest that extracellular eCBs levels can be markedly elevated by both PS and CPF. CB1-mediated signaling appears to play a role in the acute toxicity of PS but the role of eCBs in CPF toxicity remains unclear. - Highlights: • Chlorpyrifos and parathion both extensively inhibited hippocampal cholinesterase. • Functional signs were only noted with parathion. • Chlorpyrifos and parathion increased hippocampal extracellular anandamide levels. • 2-Arachidonoylglycerol levels were

  20. Hippocampus at 25

    Science.gov (United States)

    Eichenbaum, Howard; Amaral, David G.; Buffalo, Elizabeth A.; Buzsáki, György; Cohen, Neal; Davachi, Lila; Frank, Loren; Heckers, Stephan; Morris, Richard G. M.; Moser, Edvard I.; Nadel, Lynn; O'Keefe, John; Preston, Alison; Ranganath, Charan; Silva, Alcino; Witter, Menno

    2017-01-01

    The journal Hippocampus has passed the milestone of 25 years of publications on the topic of a highly studied brain structure, and its closely associated brain areas. In a recent celebration of this event, a Boston memory group invited 16 speakers to address the question of progress in understanding the hippocampus that has been achieved. Here we present a summary of these talks organized as progress on four main themes: (1) Understanding the hippocampus in terms of its interactions with multiple cortical areas within the medial temporal lobe memory system, (2) understanding the relationship between memory and spatial information processing functions of the hippocampal region, (3) understanding the role of temporal organization in spatial and memory processing by the hippocampus, and (4) understanding how the hippocampus integrates related events into networks of memories. PMID:27399159

  1. Effects of doxepin on gene expressions of Bcl-2 family, TNF-α, MAP kinase 14, and Akt1 in the hippocampus of rats exposed to stress.

    Science.gov (United States)

    Reisi, Parham; Eidelkhani, Nastaran; Rafiee, Laleh; Kazemi, Mohammad; Radahmadi, Maryam; Alaei, Hojjatallah

    2017-02-01

    Stress is one of the effective factors in the development of depressive disorders that performs some parts of its effects by affecting hippocampus. Since doxepin has been shown to have neuroprotective effects, in this study, we focused on the effects of doxepin on the expression of involved genes in neuronal survival and plasticity in the rat hippocampus following chronic stress. Male Wistar rats were divided into four groups, the control, the stress, the stress-doxepin 1 mg/kg and the stress-doxepin 5 mg/kg, respectively. To induce stress, the rats were placed within adjustable restraint chambers for 6 h/day, for 21 days. Before daily induction of the stress, rats received an i.p. injection of doxepin. At the end of experiments, expression of Bax, Bad, Bcl-2, tumor necrosis factor alpha (TNF-α), mitogen-activated protein kinase 14 (MAPK14) and serine-threonine protein kinase AKT1 genes were detected by reverse transcription polymerase chain reaction (RT-PCR) in the hippocampus. Results showed significant enhancements in expression of Bax, Bad and Bcl-2 genes in the stressed rats, whereas expression of TNF-α, MAPK14, and AKT1 genes didn't show significant differences. Doxepin could decrease the expression of Bax and Bad genes in the stress group, but had no significant effects on the expression of other genes. The present findings indicated that doxepin can probably change the pattern of gene expression in the hippocampus to maintain neurons against destructive effects of stress.

  2. LTP enhances synaptogenesis in the developing hippocampus.

    Science.gov (United States)

    Watson, Deborah J; Ostroff, Linnaea; Cao, Guan; Parker, Patrick H; Smith, Heather; Harris, Kristen M

    2016-05-01

    In adult hippocampus, long-term potentiation (LTP) produces synapse enlargement while preventing the formation of new small dendritic spines. Here, we tested how LTP affects structural synaptic plasticity in hippocampal area CA1 of Long-Evans rats at postnatal day 15 (P15). P15 is an age of robust synaptogenesis when less than 35% of dendritic spines have formed. We hypothesized that LTP might therefore have a different effect on synapse structure than in adults. Theta-burst stimulation (TBS) was used to induce LTP at one site and control stimulation was delivered at an independent site, both within s. radiatum of the same hippocampal slice. Slices were rapidly fixed at 5, 30, and 120 min after TBS, and processed for analysis by three-dimensional reconstruction from serial section electron microscopy (3DEM). All findings were compared to hippocampus that was perfusion-fixed (PF) in vivo at P15. Excitatory and inhibitory synapses on dendritic spines and shafts were distinguished from synaptic precursors, including filopodia and surface specializations. The potentiated response plateaued between 5 and 30 min and remained potentiated prior to fixation. TBS resulted in more small spines relative to PF by 30 min. This TBS-related spine increase lasted 120 min, hence, there were substantially more small spines with LTP than in the control or PF conditions. In contrast, control test pulses resulted in spine loss relative to PF by 120 min, but not earlier. The findings provide accurate new measurements of spine and synapse densities and sizes. The added or lost spines had small synapses, took time to form or disappear, and did not result in elevated potentiation or depression at 120 min. Thus, at P15 the spines formed following TBS, or lost with control stimulation, appear to be functionally silent. With TBS, existing synapses were awakened and then new spines formed as potential substrates for subsequent plasticity. © 2015 The Authors Hippocampus Published by Wiley

  3. Anti-androgenic effects of bisphenol-A on spatial memory and synaptic plasticity of the hippocampus in mice.

    Science.gov (United States)

    Fang, Zhaoqing; Zhu, Qingjie; Gu, Ting; Shen, Xiuying; Yang, Yang; Liang, Yufeng; Zhang, Zigui; Xu, Xiaohong

    2017-07-01

    Bisphenol-A (BPA) is a common environmental endocrine disruptor. Our recent studies found that exposure to BPA in both adolescent and adulthood sex-specifically impaired spatial memory in male mice. In this study, 11-week-old gonadectomied (GDX) male mice daily received subcutaneous injections of testosterone propionate (TP, 0.5mg/kg), TP and BPA (0.4 and 4mg/kg), or vehicle for 45days. The results of Morris water maze task showed that exposure to BPA did not affect the spatial memory of GDX mice but impaired that of sham (4mg/kg/day) and TP-treated GDX mice (0.4mg/kg/day). In addition, BPA reduced the level of testosterone (T) in the serum and brain of sham and TP-treated GDX mice. Exposure to BPA decreased the synaptic density and had an adverse effect on the synaptic interface of the hippocampus in sham and TP-treated GDX mice. The results of western blot analysis further showed that BPA (4mg/kg) reduced the levels of synaptic proteins (synapsin I and PSD-95) and NMDA receptor subunit NR2B in sham and TP-treated GDX mice. BPA decreased the phosphorylation of ERK1/2 but increased the phosphorylation of p38 in sham and TP-treated GDX mice. These results suggest that impairment of spatial memory and adverse effects on synaptic remodeling of hippocampal neurons in males after long-term BPA exposure is related to the anti-androgen effect of BPA. These effects of BPA may be associated with downregulated synaptic proteins and NMDA receptor through inhibiting ERKs and promoting the p38 pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. When music and long-term memory interact: effects of musical expertise on functional and structural plasticity in the hippocampus.

    Science.gov (United States)

    Groussard, Mathilde; La Joie, Renaud; Rauchs, Géraldine; Landeau, Brigitte; Chételat, Gaël; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis; Platel, Hervé

    2010-10-05

    The development of musical skills by musicians results in specific structural and functional modifications in the brain. Surprisingly, no functional magnetic resonance imaging (fMRI) study has investigated the impact of musical training on brain function during long-term memory retrieval, a faculty particularly important in music. Thus, using fMRI, we examined for the first time this process during a musical familiarity task (i.e., semantic memory for music). Musical expertise induced supplementary activations in the hippocampus, medial frontal gyrus, and superior temporal areas on both sides, suggesting a constant interaction between episodic and semantic memory during this task in musicians. In addition, a voxel-based morphometry (VBM) investigation was performed within these areas and revealed that gray matter density of the hippocampus was higher in musicians than in nonmusicians. Our data indicate that musical expertise critically modifies long-term memory processes and induces structural and functional plasticity in the hippocampus.

  5. When music and long-term memory interact: effects of musical expertise on functional and structural plasticity in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Mathilde Groussard

    Full Text Available The development of musical skills by musicians results in specific structural and functional modifications in the brain. Surprisingly, no functional magnetic resonance imaging (fMRI study has investigated the impact of musical training on brain function during long-term memory retrieval, a faculty particularly important in music. Thus, using fMRI, we examined for the first time this process during a musical familiarity task (i.e., semantic memory for music. Musical expertise induced supplementary activations in the hippocampus, medial frontal gyrus, and superior temporal areas on both sides, suggesting a constant interaction between episodic and semantic memory during this task in musicians. In addition, a voxel-based morphometry (VBM investigation was performed within these areas and revealed that gray matter density of the hippocampus was higher in musicians than in nonmusicians. Our data indicate that musical expertise critically modifies long-term memory processes and induces structural and functional plasticity in the hippocampus.

  6. Prior regular exercise reverses the decreased effects of sleep deprivation on brain-derived neurotrophic factor levels in the hippocampus of ovariectomized female rats.

    Science.gov (United States)

    Saadati, Hakimeh; Sheibani, Vahid; Esmaeili-Mahani, Saeed; Darvishzadeh-Mahani, Fatemeh; Mazhari, Shahrzad

    2014-11-01

    Previous studies indicated that brain-derived neurotrophic factor (BDNF) is the main candidate to mediate the beneficial effects of exercise on cognitive function in sleep deprived male rats. In addition, our previous findings demonstrate that female rats are more vulnerable to the deleterious effects of sleep deprivation on cognitive performance and synaptic plasticity. Therefore, the current study was designed to investigate the effects of treadmill exercise and/or sleep deprivation (SD) on the levels of BDNF mRNA and protein in the hippocampus of female rats. Intact and ovariectomized (OVX) female Wistar rats were used in the present experiment. The exercise protocol was four weeks treadmill running and sleep deprivation was accomplished using the multiple platform method. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot analysis were used to evaluate the level of BDNF mRNA and protein in the rat hippocampus respectively. Our results showed that protein and mRNA expression of BDNF was significantly (prats in compared with other groups. Furthermore, sleep deprived OVX rats under exercise conditions had a significant (pexercise can exert a protective effect against hippocampus-related functions and impairments induced by sleep deprivation probably by inducing BDNF expression. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. [Effect of puerarin on learning-memory behavior and synaptic structure of hippocampus in the aging mice induced by D-galactose].

    Science.gov (United States)

    Xu, Xiao-hong; Zhang, Zi-gui

    2002-01-01

    To study the effects of puerarin on learning-memory behavior of aging mice induced by D-galactose and its possible mechanism of action. The aging mice were induced by s.c. 0.12 g.kg-1 D-galactose for 6 weeks. The aging mice were treated with three doses of puerarin once a day for 5 weeks. The spontaneous behavior and the learning memory behavior were tested in the aging mice using open field and Y-maze at the next day after the last treatment. The structure of Gray I synaptic interface in the CA3 area of the hippocampus was quantitatively analyzed by electronic microscope and computer image processing appliance. Compared with the D-galactose control group, puerarin (60 mg.kg-1) was shown to increase significantly the spontaneous behavior and explorative response in the open field, and improve remarkablely the learning and memory ability of the aging mice induced by D-galactose. Meanwhile, the thickness of post-synaptic density (PSD) was increased, and the width of the synaptic cleft in the hippocampus CA3 area was shortened. Puerarin showed an improvement effect against the memory impairment in the modelling aging-mice induced by D-galactose. A pathological alteration of synaptic interface structure in hippocampus of the mice may be involved in the effect.

  8. A novel mechanism for the anticonvulsant effect of furosemide in rat hippocampus in vitro.

    Science.gov (United States)

    Uwera, Josiane; Nedergaard, Steen; Andreasen, Mogens

    2015-11-02

    Though both in vivo and in vitro studies have demonstrated an anticonvulsant effect of the loop diuretic furosemide, the precise mechanism behind this effect is still debated. The current study investigates the effect of furosemide on Cs-induced epileptiform activity (Cs-FP) evoked in area CA1 of rat hippocampal slices in the presence of Cs(+) (5mM) and ionotropic glutamatergic and GABAergic receptor antagonists. As this model diverges in several respects from other epilepsy models it can offer new insight into the mechanism behind the anticonvulsive effect of furosemide. The present study shows that furosemide suppresses the Cs-FP in a dose-dependent manner with a near complete block at concentrations ≥ 1.25 mM. Because furosemide targets several types of ion transporters we examined the effect of more selective antagonists. Bumetanide (20 μM), which selectively inhibits the Na-K-2Cl co-transporter (NKCC1), had no significant effect on the Cs-FP. VU0240551 (10 μM), a selective antagonist of the K-Cl co-transporter (KCC2), reduced the ictal-like phase by 51.73 ± 8.5% without affecting the interictal-like phase of the Cs-FP. DIDS (50 μM), a nonselective antagonist of Cl(-)/HCO3(-)-exchangers, Na(+)-HCO3(-)-cotransporters, chloride channels and KCC2, suppressed the ictal-like phase by 60.8 ± 8.1% without affecting the interictal-like phase. At 500 μM, DIDS completely suppressed the Cs-FP. Based on these results we propose that the anticonvulsant action of furosemide in the Cs(+)-model is exerted through blockade of the neuronal KCC2 and Na(+)-independent Cl(-)/HCO3(-)-exchanger (AE3) leading to stabilization of the activity-induced intracellular acidification in CA1 pyramidal neurons. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures

    DEFF Research Database (Denmark)

    Woldbye, David Paul Drucker; Ängehagen, Mikael; Gøtzsche, Casper René

    2010-01-01

    Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure...... suppression by neuropeptide Y in the hippocampus is predominantly mediated by Y2 receptors, which, together with neuropeptide Y, are upregulated after seizures as a compensatory mechanism. To explore whether such upregulation could prevent seizures, we overexpressed Y2 receptors in the hippocampus using...... recombinant adeno-associated viral vectors. In two temporal lobe epilepsy models, electrical kindling and kainate-induced seizures, vector-based transduction of Y2 receptor complementary DNA in the hippocampus of adult rats exerted seizure-suppressant effects. Simultaneous overexpression of Y2...

  10. p63 Expression in the Gerbil Hippocampus Following Transient Ischemia and Effect of Ischemic Preconditioning on p63 Expression in the Ischemic Hippocampus.

    Science.gov (United States)

    Lee, Jae-Chul; Cho, Geum-Sil; Kim, In Hye; Park, Joon Ha; Cho, Jeong-Hwi; Ahn, Ji Hyeon; Bae, Eun Joo; Ahn, Ji Yun; Park, Chan Woo; Cho, Jun Hwi; Kim, Young-Myeong; Won, Moo-Ho; Lee, Hui Young

    2015-05-01

    p63 is a transcription factor of p53 gene family, which are involved in development, differentiation and cell response to stress; however, its roles in ischemic preconditioning (IPC) in the brain are not clear. In the present study, we investigated the effect of IPC on p63 immunoreactivity caused by 5 min of transient cerebral ischemia in gerbils. IPC was induced by subjecting the gerbils to 2 min of transie ischemia 1 day prior to 5 min of transient ischemia. The animals were randomly assigned to four groups (sham-operated-group, ischemia-operated-group, IPC plus (+)-sham-operated-group and IPC + ischemia-operated-group). The number of viable neurons in the stratum pyramidale of the hippocampal CA1 region (CA1) was significantly increased by IPC + ischemia-operated-group compared with that in the ischemia-operated-group 5 days after ischemic insult. We found that strong p63 immunoreactivity was detected in the CA1 pyramidal neurons in the sham-operated-group, and the immunoreactivity was decreased with time after ischemia-reperfusion. In addition, strong p63 immunoreactivity was newly expressed in microglial cells of the CA1 region from 2 days after ischemia-reperfusion. In all the IPC + sham-operated-groups, p63 immunoreactivity in the CA1 pyramidal neurons was similar to that in the sham-operated-group, and the immunoreactivity was well maintained in the IPC + ischemia-operated-groups after cerebral ischemia. In brief, our present findings show that IPC dramatically protected the reduction of p63 immunoreactivity in the pyramidal neurons of the CA1 region after ischemia-reperfusion, and this result suggests that the expression of p63 may be necessary for neurons to survive after transient cerebral ischemia.

  11. Regular exercise prevents sleep deprivation associated impairment of long-term memory and synaptic plasticity in the CA1 area of the hippocampus.

    Science.gov (United States)

    Zagaar, Munder; Dao, An; Levine, Amber; Alhaider, Ibrahim; Alkadhi, Karim

    2013-05-01

    The present study aimed to investigate the effects of treadmill exercise on sleep deprivation (S-D)-induced impairment of hippocampal dependent long-term memory, late phase long-term potentiation (L-LTP) and its signaling cascade in the cornu ammonis 1 (CA1) area. Animals were conditioned to run on treadmills for 4 weeks then deprived of sleep for 24 h using the columns-in-water method. We tested the effect of exercise and/or S-D on behavioral performance using a post-learning paradigm in the radial arm water maze (RAWM) and in vivo extracellular recording in the CA1 area. The levels of L-LTP-related molecules in the CA1 area were then assessed both before and after L-LTP induction. After 24 h of S-D, spatial long-term memory impairment in the RAWM and L-LTP suppression was prevented by 4 weeks of regular exercise. Regular exercise also restored the S-D-associated decreases in the basal levels of key signaling molecules such as: calcium/calmodulin kinase IV (CaMKIV), mitogen-activated protein kinase (MAPK/ERK), phosphorylated cAMP response element-binding protein (P-CREB) and brain derived neurotrophic factor (BDNF), in the CA1 area. After L-LTP induction, regular exercise also prevented the S-D-induced down regulation of BDNF and P-CREB protein levels. The results suggest that our exercise protocol may prevent 24-h S-D-induced impairments in long-term memory and LTP by preventing deleterious changes in the basal and post-stimulation levels of P-CREB and BDNF associated with S-D.

  12. Valproic acid effects in the hippocampus and prefrontal cortex in an animal model of post-traumatic stress disorder.

    Science.gov (United States)

    Wilson, C Brad; McLaughlin, Leslie D; Ebenezer, Philip J; Nair, Anand R; Francis, Joseph

    2014-07-15

    Reactive oxygen species (ROS) and pro-inflammatory cytokines (PIC) are upregulated in post-traumatic stress disorder (PTSD). Histone deacetylase inhibitors (HDACi) modify genetic transcription and can diminish ROS and PIC escalation. They can also modulate levels of neurotransmitters such as catecholamines and serotonin (5-HT). Thus, this study sought to analyze the effects of the HDACi valproic acid (VA) on oxidative stress, inflammation, and neurotransmitter modulation via a predator exposure/psychosocial stress animal model of PTSD. PTSD-like effects were induced in male Sprague-Dawley rats (n=6/group×4 groups). The rats were secured in Plexiglas cylinders and placed in a cage with a cat for 1h on days 1, 11, and 40 of a 40-day stress regimen. PTSD rats were also subjected to psychosocial stress via daily cage cohort changes. At the conclusion of the stress regimen, the treatment group (PTSD+VA) and control group (Control+VA) rats were given VA in their drinking water for 30 days. The rats were then euthanized and their brains were dissected to remove the hippocampus and prefrontal cortex (PFC). Whole blood was collected to assess systemic oxidative stress. ROS and PIC mRNA and protein elevation in the PTSD group were normalized with VA. Anxiety decreased in this group via improved performance on the elevated plus-maze (EPM). No changes were attributed to VA in the control group, and no improvements were noted in the vehicle groups. Results indicate VA can attenuate oxidative stress and inflammation, enhance fear extinction, and correct neurotransmitter aberrancies in a rat model of PTSD. Copyright © 2014. Published by Elsevier B.V.

  13. Timing is essential for rapid effects of corticosterone on synaptic potentiation in the mouse hippocampus.

    NARCIS (Netherlands)

    Wiegert, O.; Joëls, M.; Krugers, H.

    2006-01-01

    Stress facilitates memory formation, but only when the stressor is closely linked to the learning context. These effects are, at least in part, mediated by corticosteroid hormones. Here we demonstrate that corticosterone rapidly facilitates synaptic potentiation in the mouse hippocampal CA1 area

  14. BEHAVIORAL AND BIOCHEMICAL EFFECTS OF EARLY POSTNATAL CHOLINERGIC LESION IN THE HIPPOCAMPUS

    NARCIS (Netherlands)

    GASPAR, E; HEERINGA, M; MARKEL, E; LUITEN, PGM; NYAKAS, C

    The effects of early postnatal (PD 8) intracerebroventricular injection of ethylcholine mustard aziridinium ion (AF64A) on development of open-field and cognitive behaviors and cholinergic markers in several brain areas were examined in the rat. The cholinotoxin was bilaterally administered in a

  15. [Effects of dithizone on the electroencephalogram recorded from the mouse hippocampus in vivo].

    Science.gov (United States)

    Negi, T

    1986-01-01

    In the present study the author examined the effects of dithizone on hippocampal and cortical EEG by power spectral analysis in the moving mouse. Following results were obtained. Administration of dithizone 100 mg/kg i. p. produced almost loss of electrical activities on EEG which began 409 sec after injection and lasted approximately up to 706 sec. In recovery period waveform showed shift to slower frequencies apparent by 60 min. Heart rate decreases were seen between 5 and 20 min after 100 mg/kg i. p. injection. Dithizone produced dose-dependent changes in hippocampal and heart rate activities. Abolished EEG by dithizone administration were immediately recovered by zinc-acetate application. Injection of vehicle had no significant effect on hippocampal and cortical EEG.

  16. The combined effects of developmental lead and ethanol exposure on hippocampus dependent spatial learning and memory in rats: Role of oxidative stress.

    Science.gov (United States)

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

    2016-10-01

    Either developmental lead or ethanol exposure can impair learning and memory via induction of oxidative stress, which results in neuronal damage. we examined the effect of combined exposure with lead and ethanol on spatial learning and memory in offspring and oxidative stress in hippocampus. Rats were exposed to lead (0.2% in drinking water) or ethanol (4 g/kg) either individually or in combination in 5th day gestation through weaning. On postnatal days (PD) 30, rats were trained with six trials per day for 6 consecutive days in the water maze. On day 37, a probe test was done. Also, oxidative stress markers in the hippocampus were also evaluated. Results demonstrated that lead + ethanol co-exposed rats exhibited higher escape latency during training trials and reduced time spent in target quadrant, higher escape location latency and average proximity in probe trial test. There was significant decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and increase of malondialdehyde (MDA) levels in hippocampus of animals co-exposed to lead and ethanol compared with their individual exposures. We suggest that maternal consumption of ethanol during lead exposure has pronounced detrimental effects on memory, which may be mediated by oxidative stress. Copyright © 2016. Published by Elsevier Ltd.

  17. Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus.

    Science.gov (United States)

    Joëls, Marian; Karst, Henk; Alfarez, Deborah; Heine, Vivi M; Qin, Yongjun; van Riel, Els; Verkuyl, Martin; Lucassen, Paul J; Krugers, Harm J

    2004-12-01

    It has become increasingly clear that the increase in corticosteroid levels, e.g. after a brief stressor induce molecular and cellular changes in brain, including the hippocampal formation. These effects eventually result in behavioral adaptation. Prolonged exposure to stress, though, may lead to mal-adaptation and even be a risk factor for diseases like major depression in genetically predisposed individuals. We conducted a series of experiments where changes in brain function were examined after 3 weeks of unpredictable stress. After unpredictable stress, inhibitory input to neurons involved in the hypothalamus-pituitary-adrenal (HPA) axis regulation was suppressed, which may dysregulate the axis and lead to overexposure of the brain to glucocorticoids. Furthermore, glutamate transmission in the dentate gyrus (DG) was enhanced, possibly through transcriptional regulation of receptor subunits. Combined with enhanced calcium channel expression this could increase vulnerability to cell death. Neurogenesis and apoptosis in the dentate were diminished. Synaptic plasticity was suppressed both in the dentate and CA1 area. Collectively, these effects may give rise to deficits in memory formation. Finally, we observed reduced responses to serotonin in the CA1 area, which could contribute to the onset of symptoms of depression in predisposed individuals. All of these endpoints provide potential targets for novel treatment strategies of stress-related brain disorders.

  18. Effects of feed species and HUFA composition on survival and growth of the longsnout seahorse (Hippocampus reidi

    Directory of Open Access Journals (Sweden)

    Patrick eSchubert

    2016-04-01

    Full Text Available Globally, wild seahorse populations are threatened due to, habitat destruction and unsustainable human exploitation among others. Furthermore, aquaculture-based mass-scale rearing is still uncommon due to the low survival rates of seahorse juveniles and exceptionally high feed costs. Previous studies have demonstrated the importance of both highly unsaturated fatty acid (HUFA supplies and a copepod-based rearing for seahorse survival and growth. As the latter is expensive, the question arises as to how high survival rates of seahorse juveniles can be assured under low- to moderate-cost feed regimes. In particular, it remains unknown whether the diet species or their dietary HUFA profiles determine the successful development of seahorse fry.Therefore, the aims of this study were to assess the dependence of growth and survival rates of Hippocampus reidi brood on the animal feed and to infer the impact of feed species vs. dietary HUFA profiles on juvenile growth. A nutrition experiment was conducted where juveniles were treated either with enriched Artemia nauplii (low-cost diet Art or with a mixed diet of Artemia and copepods (moderate-cost diet Art/Cop. Larval survival and growth were analyzed using Cox proportional-hazard and mixed linear model analyses. We found that i both diets enabled good survival, ii diet Art/Cop resulted in superior weight and height growth, and iii the differential effects of diets Art/Cop and Art cannot be explained by their different HUFA compositions alone.From an economical point of view, our findings of high survival rates and relatively high growth rates with the medium-cost treatment Art/Cop may open new possibilities for the large-scale rearing of seahorses. Even the application of a low-cost Art diet might be appropriate for seahorse aquacultures as both survival and growth rates are only marginally lower compared to the former diet.

  19. Fish oil and treadmill exercise have age-dependent effects on episodic memory and oxidative state of the hippocampus.

    Science.gov (United States)

    Macêdo, Patrícia Fortes Cavalcanti de; de Melo, Janatar Stella Vasconcelos; Costa, Laís Alves Ribeiro; Braz, Glauber Rudá F; de Sousa, Shirley M; Lagranha, Cláudia J; Hornsby, Manuella Batista-de-Oliveira

    2017-05-01

    There is a growing interest to better understand how lifestyle choices can improve memory functions. Treadmill exercise and long-chain n-3 polyunsaturated fatty acids found in fish oil are able to stimulate hippocampal antioxidant defenses and improve memory. The aim was to test whether fish oil and exercise can improve rat's performance on memory tasks and optimize hippocampal antioxidant state in an age-dependent manner. Therefore, young and adult rats were exercised and received fish oil during 4 weeks. The exercise was performed for 30 min/day, with the speed gradually increasing from the first to the last week. Afterwards, episodic memory was measured by the recognition of object identity and spatial location. Hippocampal oxidative state was investigated with the levels of malondialdehyde (MDA), carbonyls content, antioxidant enzymatic activity (superoxide dismutase (SOD), catalase (CAT)), and antioxidant nonenzymatic activity (reduced glutathione, sulfhydryl content). The adult rats treated with fish oil and exercise (FO&EX) were able to recognize object's shape and placement; however, FO&EX young rats had impaired spatial recognition (p < 0.05). The FO&EX young rats did not have reduced MDA or carbonyl content, though either fish oil or exercise reduced MDA (p < 0.05) and carbonyl levels (p < 0.01). Exercise increased SOD (p < 0.001) and CAT activities (p < 0.05), and fish oil enhanced SOD activity (p < 0.05) in young rats. At adulthood, exercise increased MDA levels (p < 0.05), and FO&EX reduced MDA (p < 0.001). Finally, exercise and fish oil improved nonenzymatic antioxidant defense (p < 0.05) only in adult rats. Results support age-dependent effects of fish oil and exercise on memory and oxidative state of the hippocampus during either neurodevelopment or adulthood.

  20. Antiepileptic effects of GABAb receptor activation in area CA3 of rat hippocampus.

    Science.gov (United States)

    Morrisett, R A; Lewis, D V; Swartzwelder, H S; Wilson, W A

    1993-01-15

    The role of GABAb receptor activation in the expression of both interictal and ictal phenomena was investigated in slices of area CA3 of the rat hippocampal formation. Interictal-like bursts occurred following application of high frequency trains to the Schaffer collaterals. When two bursts were triggered using paired stimuli, profound depression of the second burst was seen 150-600 ms following the first burst. GABAb receptor antagonists potently reversed the paired pulse depression of the interictal-like bursts. Reversal of the paired depression was also accomplished by increasing the extracellular concentration of K+ by 2-3 mM. Additional experiments were performed in area CA3 to determine the role of GABAb receptor activation on the expression of ictal phenomena. Electrographic seizures (EGSs) were induced by application of high frequency trains. 2-Hydroxy-saclofen (200 microM) significantly decreased the duration of trains required to elicit EGSs. Taken together, these data suggest that GABAb receptor activation has potent inhibitory effects on both ictal and interictal-like events.

  1. The mTOR and canonical Wnt signaling pathways mediate the mnemonic effects of progesterone in the dorsal hippocampus.

    Science.gov (United States)

    Fortress, Ashley M; Heisler, John D; Frick, Karyn M

    2015-05-01

    Although much is known about the neural mechanisms responsible for the mnemonic effects of 17β-estradiol (E2 ), very little is understood about the mechanisms through which progesterone (P4 ) regulates memory. We previously showed that intrahippocampal infusion of P4 in ovariectomized female mice enhances object recognition (OR) memory consolidation in a manner dependent on activation of dorsal hippocampal ERK and mTOR signaling. However, the role of specific progesterone receptors (PRs) in mediating the effects of progesterone on memory consolidation and hippocampal cell signaling are unknown. Therefore, the goals of this study were to investigate the roles of membrane-associated and intracellular PRs in mediating hippocampal memory consolidation, and identify downstream cell signaling pathways activated by PRs. Membrane-associated PRs were targeted using bovine serum albumin-conjugated progesterone (BSA-P), and intracellular PRs (PR-A, PR-B) were targeted using the intracellular PR agonist R5020. Immediately after OR training, ovariectomized mice received bilateral dorsal hippocampal infusion of vehicle, P4 , BSA-P, or R5020. OR memory consolidation was enhanced by P4 , BSA-P, and R5020. However, only P4 and BSA-P activated ERK and mTOR signaling. Furthermore, dorsal hippocampal infusion of the ERK inhibitor U0126 blocked the memory-enhancing effects of BSA-P, but not R5020. The intracellular PR antagonist RU486 blocked the memory-enhancing effects of R5020, but not BSA-P. Interestingly, P4 robustly activated canonical Wnt signaling in the dorsal hippocampus, which is consistent with our recent findings that canonical Wnt signaling is necessary for OR memory consolidation. R5020, but not BSA-P, also elicited a modest increase in canonical Wnt signaling. Collectively, these data suggest that activation of ERK signaling is necessary for membrane-associated PRs to enhance OR, and indicate a role for canonical Wnt signaling in the memory-enhancing effects of

  2. Effect of total flavonoids of Scutellaria barbata on cognitive function and nogo-A expression in the hippocampus in cerebral ischemia model in gerbils.

    Science.gov (United States)

    Zhang, Yanping; Li, Yanmei

    2016-11-01

    To explore the effect of total flavonoids of Scutellaria barbata on cognitive function and nogo-A expression in the hippocampus region in cerebral ischemia model in gerbils. 30 gerbils were randomly divided into model group, sham operation group, large dose of total flavonoids of Scutellaria barbata group (large dose group), middle dose of total flavonoids of Scutellaria barbata group (middle dose group) and small dose of total flavonoids of Scutellaria barbata group (small dose group), with 6 cases in each group. All the groups except the sham operation group were received bilateral common carotid artery ligation to establish the cerebral ischemia model in gerbils. After that, the large, middle and small doses groups were given 400mg/kg, 200mg/kg and 100mg/kg of total flavonoids of Scutellaria barbata respectively, while the other two groups were injected with sodium chloride for 4 continuous weeks. At the 5th and 8th week after modeling, the cognitive function (e.g. escape latency period and original platform crossing times) of the gerbils in the three groups were detected by Morris water maze test. Moreover, the nogo-A expressions in the hippocampus region were detected by immunohistochemical staining method at the 8th week. The escape latency period and platform crossing times at the 5th and 8th week after modeling in the large dose group were significantly higher than the rest groups (except slam operation group) (p0.05). The difference of the gray value of nogo-A positive cells in hippocampus in the large dose group was not significant compared with middle dose group and sham operation group (p>0.05), while it was significant compared with model group and small dose group (pflavonoids of Scutellaria barbata can obviously improve the cognitive function in cerebral ischemia model in gerbils by reducing nogo-A expression in the hippocampus region.

  3. Effects of lentivirus-mediated CREB expression in the dorsolateral striatum: memory enhancement and evidence for competitive and cooperative interactions with the hippocampus.

    Science.gov (United States)

    Kathirvelu, Balachandar; Colombo, Paul J

    2013-11-01

    Neural systems specialized for memory may interact during memory formation or recall, and the results of interactions are important determinants of how systems control behavioral output. In two experiments, we used lentivirus-mediated expression of the transcription factor CREB (LV-CREB) to test if localized manipulations of cellular plasticity influence interactions between the hippocampus and dorsolateral striatum. In Experiment 1, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for response learning, and impairs memory for place learning. LV-CREB in the dorsolateral striatum had no effect on response learning, but impaired place memory; a finding consistent with competition between the striatum and hippocampus. In Experiment 2, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for cue learning, and impairs memory for contextual fear conditioning. LV-CREB in the dorsolateral striatum enhanced memory for cue learning and, in contrast to our prediction, also enhanced memory for contextual fear conditioning, consistent with a cooperative interaction between the striatum and hippocampus. Overall, the current experiments demonstrate that infusion of LV-CREB in the dorsolateral striatum (1) increases levels of CREB protein locally, (2) does not alter acquisition of place, response, cue, or contextual fear conditioning, (3) facilitates memory for cue learning and contextual fear conditioning, and (4) impairs memory for place learning. Taken together, the present results provide evidence that LV-CREB in the dorsolateral striatum can enhance memory formation and cause both competitive and cooperative interactions with the hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

  4. Effect of Four Weeks Exercise Prior Preparation before Alzheimer's Induction on the Levels of Nerve Growth Factor and Beta Amyloid in the Hippocampus of Wistar Male Rats

    Directory of Open Access Journals (Sweden)

    Atabak Shahed

    2018-02-01

    Full Text Available Abstract Background: The aim of this study was to investigate the effect of four weeks exercise prior preparation before Alzheimer's induction on the levels of nerve growth factor and beta amyloid in the hippocampus of Wistar male rats Materials and Methods: 84 male Wistar rats (8 weeks old with a weighing average of 20 ± 195 grams from Pasteur Institute of Iran were prepared, and rats were randomly divided to two exercise (4 weeks aerobic training on a treadmill with a gradient of 0 degrees, 5 days a week for 4 weeks and rest groups. Then, the rats of each group were randomly assigned to 3 sub groups of 14 numbers, injection Aβ1-42, control, and non-injected. 48 hours after the last exercise session, injections into the hippocampus amyloid beta or Dimethyl sulfoxide were performed. Seven days after surgery, the rats of each group were randomly sacrificed or subjected to behavioral testing. To determine the levels of of nerve growth factor and beta amyloid Sampling was performed from the hippocampus and plasma of animals, a Morris water maze test was used for spatial memory test. Kolmogorov-Smirnov test (KS and analysis of variance were used to analyze the data. Results: The results of one-way analysis of variance showed that there was a significant difference between the levels of amylohyd of hippocampus and NGF in different groups. Also, the results of the probe test for spatial memory showed that the time spent on the target circle in the Aβ1-42 injection group was significantly lower than the other groups (p≤ 0.01. Also, the exercise and exercise + sham groups had a significantly better performance than control group. Conclusion: It seems that performing physical activity before induction of Alzheimer's in rats is a kind of countermeasures and preeclampsia with physiological disorders and progression of the disease.

  5. Prenatal stress in rat causes long-term spatial memory deficit and hippocampus MRI abnormality: differential effects of postweaning enriched environment.

    Science.gov (United States)

    Lui, Chun Chung; Wang, Jia-Yi; Tain, You-Lin; Chen, Yu-Chieh; Chang, Kow-Aung; Lai, Ming-Chi; Huang, Li-Tung

    2011-02-01

    Prenatal stress (PS) can cause long-term hippocampus alternations in structure and plasticity in adult offspring. Enriched environment (EE) has an effect in rescuing a variety of neurological disorders. Pregnant dams were left undisturbed (prenatal control, PC) or restrained 6h per day from days 14 to 21 (prenatal stress, PS). Control and prenatal stressed offspring rats were subjected to a standard rearing environment (SE) or an EE on postnatal days 22-120 (PC/SE PC/EE, PS/SE, and PS/EE; n=5, each group). At ∼4 months of age, all rats underwent Morris water maze test and brain MRI examination. Hippocampi were then dissected for biochemical analyses, including, Western blot for NMDA receptor (NR) subunits and synaptophysin and RT-PCR forβ1 integrin and tissue-plasminogen activator (t-PA). MRI showed all 5 rats in the PS/SE group and 5 in the PS/EE group exhibited increased signals in bilateral hippocampus and increased T2 time in the PS/SE group. Exposure to EE treatment on postnatal days 22-120 counteracted the deficit in spatial memory and increased NR1 protein expression, but it did not affect the rate of high signals and increased T2 time, decreased NR2, synaptophysin, β1 integrin and t-PA mRNA expressions in PS adult offspring. The results of this study indicate PS in rats causes long-term spatial memory deficits and gross hippocampus pathology. Postnatal EE treatment has differential benefits in terms of spatial learning, signaling molecules, and gross hippocampus pathology. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Effect of soy milk on circulating 17- β estradiol, number of neurons in cerebral cortex and hippocampus and determination of their ratio in neonatal ovariectomized rats.

    Science.gov (United States)

    Marzban Abbasabadi, Behrokh; Tadjalli, Mina

    2016-01-01

    This study was conducted to evaluate the effect of soy milk on serum 17- β estradiol level and number of neurons in cerebral cortex and hippocampus as well as determination of the ratio of neurons in cortical and hippocampal regions in neonatal ovariectomized rats. Thirty female rats (one day old) were divided into six groups of five. At day 7, ovariectomy surgery was performed in four groups and two other groups were assumed as sham and control groups. Three groups of ovareictomaized rats were fed with soy milk at the doses of 0.75, 1.50 and 3.00 mL kg -1 per day since they were 14. At day 60, the blood samples were collected to measure the17- β estradiol concentration, and then the brain of rats were prepared for histological studies. The serum 17- β estradiol level significantly increased in ovariectomized rats fed with soy milk compared to ovariectomized rats with no soy milk supplementation. In addition, the results showed that soy milk significantly increased the number of neurons in CA1, CA2 and dentate gyrus regions of hippocampus and granular layer of cerebral cortex in ovariectomized rats, whereas there was no significant change in number of neurons in CA3 zone of hippocampus and molecular, pyramidal and multiform layers of cerebral cortex in ovariectomized rats fed with soy milk. The ratio of cerebral cortex neurons to hippocampal neurons had no significant changes among the experimental groups.

  7. [Effect of Yangxue Qingnao Granule on the Expression of CD11b in CA1 Region of Hippocampus of Vascular Dementia Rats].

    Science.gov (United States)

    Li, Jing; Ma, Yuan-yuan; Liu, Bin; Mao, Wen-jing; Zhang, Jin-xia; Li, Shi-ying

    2016-05-01

    To observe the effect of Yangxue Qingnao Granule (YQG) on the expression of CD11b in CA1 region of hippocampus of vascular dementia rats, and to explore its regulation on microglias. Totally 144 SD rats were randomly divided into the sham-operation group, the vascular dementia model group (model), and the YQG treated group (treated). The vascular dementia rat model was prepared by modified Pulsinelli's four-vessel occlusion. Rats in the sham-operation group and the model group were administered with normal saline -(at the daily dose of 10 mL/kg) by gastrogavage, while those in the treated group were administered with YQG (0.32 g/mL, at the daily dose of 10 mL/kg) by gastrogavage. All administration was performed once per day for 8 successive weeks. The expression of CD11b in CA1 region of hippocampus of vascular dementia rats was detected at week 1, 2, 4, and 8, respectively. Compared with the sham-operation group, the expression of CD11b in CA1 region of hippocampus of vascular dementia rats were significantly enhanced in the model group at each time point (P vascular dementia rats significantly decreased in the treated group at each time point (P vascular dementia rats, and YQG could inhibit activation and proliferation of microglias.

  8. Long-term green tea catechin administration prevents spatial learning and memory impairment in senescence-accelerated mouse prone-8 mice by decreasing Abeta1-42 oligomers and upregulating synaptic plasticity-related proteins in the hippocampus.

    Science.gov (United States)

    Li, Q; Zhao, H F; Zhang, Z F; Liu, Z G; Pei, X R; Wang, J B; Li, Y

    2009-10-20

    The senescence-accelerated mouse prone-8 (SAMP8) is characterized by early onset of learning and memory deficits along with spontaneous overproduction of soluble beta-amyloid peptide (Abeta) in the brain. In our study, 4 month old male SAMP8 mice were orally administered 0.05% and 0.1% green tea catechins (GTC, w/v) in drinking water for 6 months. We found that a supplementation with 0.05% or 0.1% GTC prevented spatial learning and memory impairments of mice in the Morris water maze. Better performance of GTC-treated mice was associated with decreased levels of Abeta(1-42) oligomers in the hippocampus. The activity of the protein kinase A/cAMP-response element binding protein (PKA/CREB) pathway, one of the molecular targets of Abeta oligomers which is crucial for late long-term potentiation and long-term memory formation, was significantly increased after GTC administration. We also found that chronic 0.05% or 0.1% GTC consumption prevented the reductions of three representative proteins of synaptic function and synaptic structure, including brain-derived neurotrophic factor(BDNF), post-synaptic density protein-95 (PSD95) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). These results demonstrated that long-term 0.05% or 0.1% green tea catechin administration may prevent spatial learning and memory decline of SAMP8 mice by decreasing Abeta(1-42) oligomers and upregulating synaptic plasticity-related proteins in the hippocampus.

  9. Impact of video games on plasticity of the hippocampus.

    Science.gov (United States)

    West, G L; Konishi, K; Diarra, M; Benady-Chorney, J; Drisdelle, B L; Dahmani, L; Sodums, D J; Lepore, F; Jolicoeur, P; Bohbot, V D

    2017-08-08

    The hippocampus is critical to healthy cognition, yet results in the current study show that action video game players have reduced grey matter within the hippocampus. A subsequent randomised longitudinal training experiment demonstrated that first-person shooting games reduce grey matter within the hippocampus in participants using non-spatial memory strategies. Conversely, participants who use hippocampus-dependent spatial strategies showed increased grey matter in the hippocampus after training. A control group that trained on 3D-platform games displayed growth in either the hippocampus or the functionally connected entorhinal cortex. A third study replicated the effect of action video game training on grey matter in the hippocampus. These results show that video games can be beneficial or detrimental to the hippocampal system depending on the navigation strategy that a person employs and the genre of the game.Molecular Psychiatry advance online publication, 8 August 2017; doi:10.1038/mp.2017.155.

  10. The hippocampus, medial prefrontal cortex, and selective memory retrieval: evidence from a rodent model of the retrieval-induced forgetting effect.

    Science.gov (United States)

    Wu, Jade Q; Peters, Greg J; Rittner, Pedro; Cleland, Thomas A; Smith, David M

    2014-09-01

    Inhibition is an important component of many cognitive functions, including memory. For example, the retrieval-induced forgetting (RIF) effect occurs when extra practice with some items from a study list inhibits the retrieval of the nonpracticed items relative to a baseline condition that does not involve extra practice. Although counterintuitive, the RIF phenomenon may be important for resolving interference by inhibiting potentially competing retrieval targets. Neuroimaging studies suggest that the hippocampus and prefrontal cortex are involved in the RIF effect, but controlled lesion studies have not yet been performed. We developed a rodent model of the RIF training procedure and trained control rats and rats with temporary inactivation of the hippocampus or medial prefrontal cortex (mPFC). Rats were trained on a list of odor cues, presented in cups of digging medium with a buried reward, followed by additional practice trials with a subset of the cues. We then tested the rats' memories for the cues and their association with reward by presenting them with unbaited cups containing the test odorants and measuring how long they persisted in digging. Control rats exhibited a robust RIF effect in which memory for the nonpracticed odors was significantly inhibited. Thus, extra practice with some odor cues inhibited memory for the others, relative to a baseline condition that involved an identical amount of training. Inactivation of either the hippocampus or the mPFC blocked the RIF effect. We also constructed a computational model of a representational learning circuit to simulate the RIF effect. We show in this model that "sideband suppression" of similar memory representations can reproduce the RIF effect and that alteration of the suppression parameters and learning rate can reproduce the lesion effects seen in our rats. Our results suggest that the RIF effect is widespread and that inhibitory processes are an important feature of memory function. © 2014 Wiley

  11. Frozen fruit pulp of Euterpe oleraceae Mart. (Acai) prevents hydrogen peroxide-induced damage in the cerebral cortex, cerebellum, and hippocampus of rats.

    Science.gov (United States)

    Spada, Patricia D S; Dani, Caroline; Bortolini, Giovana V; Funchal, Claudia; Henriques, João A P; Salvador, Mirian

    2009-10-01

    Oxidative stress is implicated in several human illnesses, including neurological disorders such as Parkinson's and Alzheimer's diseases. Acai is largely consumed in Brazil and contains high levels of antioxidant compounds. This work aims to study the antioxidant activity of acai frozen fruit pulp in the cerebral cortex, hippocampus, and cerebellum of rats treated with the oxidizing agent hydrogen peroxide (H(2)O(2)). Pretreatment of tissue with acai decreased H(2)O(2)-induced damage of both lipids and proteins in all tissues tested. This fruit was also able to reduce the activities of the antioxidant enzymes superoxide dismutase and catalase to basal levels. We observed a negative correlation between the polyphenol content of acai and the levels of lipid (r = -0.689; P data suggest that acai has a positive contribution in the development of age-related neurodegenerative diseases.

  12. Effects of combined prenatal stress and toluene exposure on apoptotic neurodegeneration in cerebellum and hippocampus of rats

    DEFF Research Database (Denmark)

    Ladefoged, Ole; Hougaard, Karin Sørig; Hass, Ulla

    2004-01-01

    Pregnant Wistar rats were exposed to 1500 ppm toluene 6 hr/day from gestational day 7-20 or to chronical mild stress from gestational day 9-20 as single exposure or in combination. Behavioural, immunohistopathological, molecular biological, and neurochemical methods were applied to investigate...... in the number of TUNEL positive cells was identified in cerebellum at postnatal day 22. There was no statistically significant influence of exposure except that DNA-laddering in cerebellum at postnatal day 27 was increased by toluene exposure. Caspase-3 activity decreased in cerebellum and hippocampus with age....... At postnatal day 6 stress and toluene, when singly exposed, increased activity in cerebellum whereas co-exposure to stress and toluene did not. Stress increased caspase-3 activity in hippocampus postnatal day 22. There was overall consistency between the results obtained by the three supplementary methods...

  13. Adolescent and adult rats differ in the amnesic effects of acute ethanol in two hippocampus-dependent tasks: Trace and contextual fear conditioning.

    Science.gov (United States)

    Hunt, Pamela S; Barnet, Robert C

    2016-02-01

    Experience-produced deficits in trace conditioning and context conditioning have been useful tools for examining the role of the hippocampus in learning. It has also been suggested that learning in these tasks is especially vulnerable to neurotoxic effects of alcohol during key developmental periods such as adolescence. In five experiments we systematically examined the presence and source of age-dependent vulnerability to the memory-disrupting effects of acute ethanol in trace conditioning and contextual fear conditioning. In Experiment 1a pre-training ethanol disrupted trace conditioning more strongly in adolescent (postnatal day, PD30-35) than adult rats (PD65-75). In Experiment 1b when pre-training ethanol was accompanied by pre-test ethanol no deficit in trace conditioning was observed in adolescents, suggesting that state-dependent retrieval failure mediated ethanol's disruption of trace conditioning at this age. Experiment 2a and b examined the effect of ethanol pretreatment on context conditioning. Here, adult but not adolescent rats were impaired in conditioned freezing to context cues. Experiment 2c explored state-dependency of this effect. Pre-training ethanol continued to disrupt context conditioning in adults even when ethanol was also administered prior to test. Collectively these findings reveal clear age-dependent and task-dependent vulnerabilities in ethanol's disruptive effects on hippocampus-dependent memory. Adolescents were more disrupted by ethanol in trace conditioning than adults, and adults were more disrupted by ethanol in context conditioning than adolescents. We suggest that adolescents may be more susceptible to changes in internal state (state-dependent retrieval failure) than adults and that ethanol disrupted performance in trace and context conditioning through different mechanisms. Relevance of these findings to theories of hippocampus function is discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Analysis of ribosomal protein S6 baseline phosphorylation and effect of tau pathology in the murine brain and human hippocampus.

    Science.gov (United States)

    Klingebiel, Maria; Dinekov, Maja; Köhler, Christoph

    2017-03-15

    We examined the distribution pattern of the phosphorylated 40S ribosomal subunit protein S6, a downstream target of the mTOR pathway, in the brains of 24-months-old human tau transgenic pR5 mice, non-transgenic littermates and in human hippocampi. We studied baseline levels of phosphorylated S6 and a possible effect of tau pathology. S6 phosphorylated at Ser235/236 (pS6Ser235/236) or Ser240/244 (pS6Ser240/244) has been used as a read-out of mTOR activity in several studies. The mTOR pathway regulates a wide variety of cellular functions including cell growth, ribosome biosynthesis, translational control and autophagy. Its dysregulation might underlie the neurodegenerative pathology of Alzheimer's disease and other tauopathies. pS6Ser235/236 and pS6Ser240/244 immunoreactivity in the mouse brain were widespread and similar distributed, but intensive pS6Ser235/236 immunoreactivity was more selective, especially highlighting certain brainstem regions. In the human hippocampus mainly granulovacuolar inclusions in neurons displayed pS6Ser235/236 immunoreactivity. In contrast, a considerable number of neurons displayed pS6Ser240/244 immunoreactivity in the cytoplasm without labeling of granulovacuolar inclusions. Except for a tendency of lower numbers of intensely phosphorylated S6-positive neurons in pR5 mice, the pattern of distribution of pS6Ser235/236 and pS6Ser240/244 immunoreactivity was largely unchanged when compared with non-transgenic mice and also when human hippocampi from AD cases and controls were compared. Similar to pR5 mice most neurons with hyper-phosphorylated tau in human hippocampi displayed no or only weak labeling for phosphorylated S6, suggesting that phosphorylated S6 is not especially associated with pathological tau, but is rather a feature of unaffected neurons. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Dose-response and relative biological effectiveness of fast neutrons: induction of apoptosis and inhibition of neurogenesis in the hippocampus of adult mice.

    Science.gov (United States)

    Yang, Miyoung; Kim, Joong-Sun; Song, Myoung-Sub; Kim, Jong-Choon; Shin, Taekyun; Lee, Seung-Sook; Kim, Sung-Ho; Moon, Changjong

    2010-06-01

    Our study compared the effects of high linear energy transfer (LET) fast neutrons on the induction of apoptosis and reduction of neurogenesis in the hippocampus of adult ICR mice with those of low-LET (60)Co gamma-rays, to evaluate the relative biological effectiveness (RBE) of fast neutrons in the adult hippocampal dentate gyrus (DG). The mice were exposed to 35 MeV fast neutrons or (60)Co gamma-rays. We evaluated acutely the incidence of apoptosis and expression of Ki-67 (a protein marker for cell proliferation originally defined by the monoclonal antibody Kiel-67) and doublecortin (DCX: an immature progenitor neuron marker) in the hippocampus after a single whole-body irradiation. The number of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling (TUNEL)-positive apoptotic nuclei in the DG increased and both Ki-67- and DCX-positive cells declined in a dose-dependent pattern, with fast neutrons or gamma-rays. In the hippocampus, which showed an apoptosis frequency between 2 and 8 per DG, the RBE of fast neutrons was approximately 1.9. Additionally, the inhibitory effects of fast neutrons on the expression frequencies of Ki-67 (4-8) and DCX (8-32) were approximately 3.2 and 2.5 times, respectively, the effects of gamma-rays at the same dose. Increased apoptotic cell death and decreased neurogenesis in the hippocampal DG were seen in a dose-dependent pattern after exposure to fast neutrons and gamma-rays. In addition, the different rate of hippocampal neurogenesis between different radiation qualities may be an index of RBE.

  16. Sleep restriction suppresses neurogenesis induced by hippocampus-dependent learning.

    Science.gov (United States)

    Hairston, Ilana S; Little, Milton T M; Scanlon, Michael D; Barakat, Monique T; Palmer, Theo D; Sapolsky, Robert M; Heller, H Craig

    2005-12-01

    Sleep deprivation impairs hippocampal-dependent learning, which, in turn, is associated with increased survival of newborn cells in the hippocampus. We tested whether the deleterious effects of sleep restriction on hippocampus-dependent memory were associated with reduced cell survival in the hippocampus. We show that sleep restriction impaired hippocampus-dependent learning and abolished learning-induced neurogenesis. Animals were trained in a water maze on either a spatial learning (hippocampus-dependent) task or a nonspatial (hippocampus-independent) task for 4 days. Sleep-restricted animals were kept awake for one-half of their rest phase on each of the training days. Consistent with previous reports, animals trained on the hippocampus-dependent task expressed increased survival of newborn cells in comparison with animals trained on the hippocampus-independent task. This increase was abolished by sleep restriction that caused overall reduced cell survival in all animals. Sleep restriction also selectively impaired spatial learning while performance in the nonspatial task was, surprisingly, improved. Further analysis showed that in both training groups fully rested animals applied a spatial strategy irrespective of task requirements; this strategy interfered with performance in the nonspatial task. Conversely, in sleep-restricted animals, this preferred spatial strategy was eliminated, favoring the use of nonspatial information, and hence improving performance in the nonspatial task. These findings suggest that sleep loss altered behavioral strategies to those that do not depend on the hippocampus, concomitantly reversing the neurogenic effects of hippocampus-dependent learning.

  17. Preventive Effects of Catechins on Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Xiao-Qiang Chen

    2016-12-01

    Full Text Available Catechins are polyphenolic phytochemicals with many important physiological activities that play a multifaceted health care function in the human body, especially in the prevention of cardiovascular disease. In this paper, various experimental and clinical studies have revealed the role of catechins in the prevention and treatment of cardiovascular disorders, and we review the preventive effects of catechins on cardiovascular disease from the following aspects: Regulating lipid metabolism, regulating blood lipid metabolism, vascular endothelial protection, and reducing blood pressure.

  18. Preventive Effects of Catechins on Cardiovascular Disease.

    Science.gov (United States)

    Chen, Xiao-Qiang; Hu, Ting; Han, Yu; Huang, Wei; Yuan, Hai-Bo; Zhang, Yun-Tian; Du, Yu; Jiang, Yong-Wen

    2016-12-21

    Catechins are polyphenolic phytochemicals with many important physiological activities that play a multifaceted health care function in the human body, especially in the prevention of cardiovascular disease. In this paper, various experimental and clinical studies have revealed the role of catechins in the prevention and treatment of cardiovascular disorders, and we review the preventive effects of catechins on cardiovascular disease from the following aspects: Regulating lipid metabolism, regulating blood lipid metabolism, vascular endothelial protection, and reducing blood pressure.

  19. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  20. Estriol preserves synaptic transmission in the hippocampus during autoimmune demyelinating disease.

    Science.gov (United States)

    Ziehn, Marina O; Avedisian, Andrea A; Dervin, Shannon M; O'Dell, Thomas J; Voskuhl, Rhonda R

    2012-08-01

    Cognitive deficits occur in over half of multiple sclerosis patients, with hippocampal-dependent learning and memory commonly impaired. Data from in vivo MRI and post-mortem studies in MS indicate that the hippocampus is targeted. However, the relationship between structural pathology and dysfunction of the hippocampus in MS remains unclear. Hippocampal neuropathology also occurs in experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS. Although estrogen treatment of EAE has been shown to be anti-inflammatory and neuroprotective in the spinal cord, it is unknown if estrogen treatment may prevent hippocampal pathology and dysfunction. In the current study we examined excitatory synaptic transmission during EAE and focused on pathological changes in synaptic protein complexes known to orchestrate functional synaptic transmission in the hippocampus. We then determined if estriol, a candidate hormone treatment, was capable of preventing functional changes in synaptic transmission and corresponding hippocampal synaptic pathology. Electrophysiological studies revealed altered excitatory synaptic transmission and paired-pulse facilitation (PPF) during EAE. Neuropathological experiments demonstrated that there were decreased levels of pre- and post-synaptic proteins in the hippocampus, diffuse loss of myelin staining and atrophy of the pyramidal layers of hippocampal cornu ammonis 1 (CA1). Estriol treatment prevented decreases in excitatory synaptic transmission and lessened the effect of EAE on PPF. In addition, estriol treatment prevented several neuropathological alterations that occurred in the hippocampus during EAE. Cross-modality correlations revealed that deficits in excitatory synaptic transmission were significantly correlated with reductions in trans-synaptic protein binding partners known to modulate excitatory synaptic transmission. To our knowledge, this is the first report describing a functional correlate to hippocampal

  1. Chewing Maintains Hippocampus-Dependent Cognitive Function

    Science.gov (United States)

    Chen, Huayue; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2015-01-01

    Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research. PMID:26078711

  2. Sex-dependent effects of developmental exposure to different pesticides on spatial learning. The role of induced neuroinflammation in the hippocampus.

    Science.gov (United States)

    Gómez-Giménez, Belén; Llansola, Marta; Hernández-Rabaza, Vicente; Cabrera-Pastor, Andrea; Malaguarnera, Michele; Agusti, Ana; Felipo, Vicente

    2017-01-01

    The use of pesticides has been associated with impaired neurodevelopment in children. The aims of this work were to assess: 1) the effects on spatial learning of developmental exposure to pesticides 2) if the effects are sex-dependent and 3) if hippocampal neuroinflammation is associated with the impairment of spatial learning. We analyzed the effects of developmental exposure to four pesticides: chlorpyrifos, carbaryl, endosulfan and cypermethrin. Exposure was from gestational day 7 to post-natal day 21 and spatial learning and memory was assessed when the rats were young adults. The effects of pesticides on spatial learning were pesticide and gender-dependent. Carbaryl did not affect spatial learning in males or females. Endosulfan and chlorpyrifos impaired learning in males but not in females. Cypermethrin improved spatial learning in the Morris water maze both in males and females while impaired learning in the radial maze only in males. Spatial learning ability was lower in control female rats than in males. All pesticides induced neuroinflammation, increasing IL-1b content in the hippocampus and there is a negative correlation between IL-1b levels in the hippocampus and spatial learning. Neuroinflammation would contribute to the effects of pesticides on spatial learning. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. [Effects of Rhodiola rosea on level of 5-hydroxytryptamine, cell proliferation and differentiation, and number of neuron in cerebral hippocampus of rats with depression induced by chronic mild stress].

    Science.gov (United States)

    Qin, Ya-jing; Zeng, Yuan-shan; Zhou, Chun-chun; Li, Yan; Zhong, Zhi-qiang

    2008-12-01

    To explore the effects of Rhodiola rosea on the level of 5-hydroxytryptamine (5-HT), cell proliferation and differentiation, and number of neuron in cerebral hippocampus of rats with depression induced by chronic mild stress. Fifty rats were divided into 5 groups: normal control, untreated, negative control, positive control and Rhodiola rosea-treated groups. There were 10 rats in each group. Except for normal control group, depression was induced in rats by chronic mild stress. The depressive rats in the other four groups were intragastrically administered with 0.5% sodium carboxymethycellulose, fluoxetine and Rhodiola rosea for 3 weeks. After the treatment, the content of 5-HT in the hippocampus was detected by high-performance liquid chromatography. The proliferating cells and differentiated cells in the hippocampus were labeled by bromodeoxyuridine (BrdU) or/and beta-tubulin III immunohistochemistry, and the number of hippocampal neurons was counted by morphometry. Compared with the normal control group, the content of 5-HT, number of BrdU positive cells, percentage of BrdU and beta-tubulin III double labeled cells and number of neurons in cerebral hippocampus in the Rhodiola rosea-treated group were increased and recovered to normal level. Rhodiola rosea may enhance the level of 5-HT and promote the proliferation and differentiation of neural stem cells in the hippocampus of the depressive rats, and may play a role in saving injured neurons of the hippocampus.

  4. Anxiolytic effects of muscarinic acetylcholine receptors agonist oxotremorine in chronically stressed rats and related changes in BDNF and FGF2 levels in the hippocampus and prefrontal cortex.

    Science.gov (United States)

    Di Liberto, Valentina; Frinchi, Monica; Verdi, Vincenzo; Vitale, Angela; Plescia, Fulvio; Cannizzaro, Carla; Massenti, Maria F; Belluardo, Natale; Mudò, Giuseppa

    2017-02-01

    In depressive disorders, one of the mechanisms proposed for antidepressant drugs is the enhancement of synaptic plasticity in the hippocampus and cerebral cortex. Previously, we showed that the muscarinic acetylcholine receptor (mAChR) agonist oxotremorine (Oxo) increases neuronal plasticity in hippocampal neurons via FGFR1 transactivation. Here, we aimed to explore (a) whether Oxo exerts anxiolytic effect in the rat model of anxiety-depression-like behavior induced by chronic restraint stress (CRS), and (b) if the anxiolytic effect of Oxo is associated with the modulation of neurotrophic factors, brain-derived neurotrophic factor (BDNF) and fibroblast growth factor-2 (FGF2), and phosphorylated Erk1/2 (p-Erk1/2) levels in the dorsal or ventral hippocampus and in the medial prefrontal cortex. The rats were randomly divided into four groups: control unstressed, CRS group, CRS group treated with 0.2 mg/kg Oxo, and unstressed group treated with Oxo. After 21 days of CRS, the groups were treated for 10 days with Oxo or saline. The anxiolytic role of Oxo was tested by using the following: forced swimming test, novelty suppressed feeding test, elevated plus maze test, and light/dark box test. The hippocampi and prefrontal cortex were used to evaluate BDNF and FGF2 protein levels and p-Erk1/2 levels. Oxo treatment significantly attenuated anxiety induced by CRS. Moreover, Oxo treatment counteracted the CRS-induced reduction of BDNF and FGF2 levels in the ventral hippocampus and medial prefrontal cerebral cortex CONCLUSIONS: The present study showed that Oxo treatment ameliorates the stress-induced anxiety-like behavior and rescues FGF2 and BDNF levels in two brain regions involved in CRS-induced anxiety, ventral hippocampal formation, and medial prefrontal cortex.

  5. Effectiveness of Crime Prevention through Environmental Design ...

    African Journals Online (AJOL)

    This study examined crime prevention strategies vis-a-vis perceived residents. feeling of safety in Osogbo Nigeria. The survey was conducted using systematic sampling. Four (4) crime prevention approaches were identified in the study area. Residents. perception of effectiveness of these safety strategies measured ...

  6. Comparative effectiveness of malaria preventive measures on ...

    African Journals Online (AJOL)

    The burden of malaria and its associated problems in pregnancy can be reduced by the use of different malaria preventive measures. This study was conducted to determine the comparative effectiveness of three different malaria preventive measures on populations of parturient in Abeokuta, Ogun State, Nigeria.

  7. Effect of complex aerobic physical exercise on PSD-95 in the hippocampus and on cognitive function in juvenile mice

    Science.gov (United States)

    Satriani, W. H.; Redjeki, S.; Kartinah, N. T.

    2017-08-01

    Increased neuroplasticity induced by complex aerobic physical exercise is associated with improved cognitive function in adult mice. Increased cognitive function is assumed to be based on increased synapse formation. One of the regions of the brain that is important in cognitive function is the hippocampus, which plays a role in memory formation. Post synaptic density-95 (PSD-95) is an adhesion protein of the post-synaptic density scaffolding that is essential to synaptic stabilization. As we age, the PSD-95 molecule matures the synapses needed for the formation of the basic circuitry of the nervous system in the brain. However, during the growth period, synapse elimination is higher than its formation. This study aims to determine whether complex aerobic exercise can improve cognitive function and PSD-95 levels in the hippocampus of juvenile mice during their growth stage. The mice performed complex aerobic exercise starting at five weeks of age and continuing for seven weeks with a gradual increase of 8 m/min. At eight weeks it was increased to 10 m/min. The exercise was done for five days of each week. The subjects of the study were tested for cognition one week before being sacrificed (at 12 weeks). The PSD-95 in the hippocampus was measured with ELISA. The results showed that there was a significant difference in cognitive function, where p exercise and a control group that did not. However, the PSD-95 levels did not differ significantly between the two groups. The results of this study indicate that early complex aerobic exercise can improve cognitive ability in adulthood but does not increase the levels of PSD-95 in adults.

  8. Effects of intermittent fasting on age-related changes on Na,K-ATPase activity and oxidative status induced by lipopolysaccharide in rat hippocampus.

    Science.gov (United States)

    Vasconcelos, Andrea Rodrigues; Kinoshita, Paula Fernanda; Yshii, Lidia Mitiko; Marques Orellana, Ana Maria; Böhmer, Ana Elisa; de Sá Lima, Larissa; Alves, Rosana; Andreotti, Diana Zukas; Marcourakis, Tania; Scavone, Cristoforo; Kawamoto, Elisa Mitiko

    2015-05-01

    Chronic neuroinflammation is a common characteristic of neurodegenerative diseases, and lipopolysaccharide (LPS) signaling is linked to glutamate-nitric oxide-Na,K-ATPase isoforms pathway in central nervous system (CNS) and also causes neuroinflammation. Intermittent fasting (IF) induces adaptive responses in the brain that can suppress inflammation, but the age-related effect of IF on LPS modulatory influence on nitric oxide-Na,K-ATPase isoforms is unknown. This work compared the effects of LPS on the activity of α1,α2,3 Na,K-ATPase, nitric oxide synthase gene expression and/or activity, cyclic guanosine monophosphate, 3-nitrotyrosine-containing proteins, and levels of thiobarbituric acid-reactive substances in CNS of young and older rats submitted to the IF protocol for 30 days. LPS induced an age-related effect in neuronal nitric oxide synthase activity, cyclic guanosine monophosphate, and levels of thiobarbituric acid-reactive substances in rat hippocampus that was linked to changes in α2,3-Na,K-ATPase activity, 3-nitrotyrosine proteins, and inducible nitric oxide synthase gene expression. IF induced adaptative cellular stress-response signaling pathways reverting LPS effects in rat hippocampus of young and older rats. The results suggest that IF in both ages would reduce the risk for deficits on brain function and neurodegenerative disorders linked to inflammatory response in the CNS. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Omega-3 fatty acids prevent LPS-induced passive avoidance learning and memory and CaMKII-α gene expression impairments in hippocampus of rat.

    Science.gov (United States)

    Dehkordi, Neda Gholamian; Noorbakhshnia, Maryam; Ghaedi, Kamran; Esmaeili, Abolghasem; Dabaghi, Mohammad

    2015-04-01

    Neuroinflammation is considered to be a major factor in several neurodegenerative diseases. Recently, the polyunsaturated fatty acid omega-3 has been shown to have anti-inflammatory effects and might play an effective role in improving memory impairment due to inflammation. In order to test this, we stimulated neuroinflammation in an animal model and induced memory dysfunction as measured by reduced retention of passive avoidance learning (PAL) and altered expression of CaMKII-α, a gene known to be crucial for memory formation. We then investigated whether treatment with dietary omega-3 prevents inflammation-induced memory dysfunction in this model. Male wistar rats (200-220 g) were fed either a control diet or a diet containing omega-3 (400mg/kg, po) for 1 month prior. Rats then received injection of either saline or LPS (500 μg/kg, ip) and were subjected to the PAL acquisition task. The retention test was performed 24h later, and animals were sacrificed immediately. Hippocampi were dissected and stored at -80°C. Finally, TNF-α levels and CaMKII-α gene expression were measured by ELISA and qRT-PCR, respectively. We found that LPS treatment significantly impaired PAL and memory, increased TNF-α levels and impaired CaMKII-α gene expression. In control and LPS-injected animals, pre-treatment with omega-3 improved performance on the PAL task and increased CAMKII-α gene expression. Taken together, these data suggest that dietary omega-3 may improve cognitive function and provide a potential therapy for memory impairment due to neuroinflammation. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  10. Methyllycaconitine (MLA) blocks the nicotine evoked anxiogenic effect and 5-HT release in the dorsal hippocampus: possible role of alpha7 receptors.

    Science.gov (United States)

    Tucci, S A; Genn, R F; File, S E

    2003-03-01

    Nicotine has bimodal effects on anxiety, with low doses having an anxiolytic effect and high doses having an anxiogenic effect. The dorsal hippocampus is one of the brain areas that mediate the anxiogenic effect of nicotine through enhanced 5-HT release, but the nAChR subtype(s) that mediate these effects are not known. Intrahippocampal administration of a high dose of nicotine (1 micro g, 4.3 mM) had an anxiogenic effect in the social interaction test that was reversed by co-administration of a behaviourally inactive dose (1.9 ng, 4.3 micro M) of methyllycaconitine (MLA), which is an antagonist at alpha7 and alpha3 nAChR subunits. At a dose (0.8 ng, 4.3 micro ;M) at which its actions would be specific to alpha4beta2 and alpha3beta2 nAChRs dihydro-beta-erythroidine (DHbetaE) was unable to reverse nicotine's anxiogenic effect. Reversal was obtained with a 10-fold higher, but receptor non-specific concentration of DHbetaE (7.8ng, 43 micro M), suggesting that the DHbetaE reversal might have been due to action at alpha7 nAChRs. Exposure of hippocampal slices to MLA (0.25, 05, 1 and 10 micro M) significantly reduced the increase in [(3)H]5-HT release evoked by nicotine (100 micro M). DHbetaE (0.1-0.5 micro M) failed to reverse this effect of nicotine on [(3)H]5-HT release, although higher concentrations (1 and 10 micro M), at which alpha7 subunits would also be affected, were able to do so. Because of the lack of effects of low, receptor specific concentrations of DHbetaE, it is more likely that the MLA reversal of both nicotine's anxiogenic effect and its stimulation of [(3)H]5-HT release is due to action at alpha7 than at alpha3 units. This is perhaps also more likely because the alpha7 receptors are highly expressed in the dorsal hippocampus, whereas the alpha3 subunits are much less abundant. However, what is most important is that, in the dorsal hippocampus, nicotine's anxiogenic effect and induced release of [(3)H]5-HT are mediated by non alpha4beta2 nAChRs, which

  11. The antioxidant effect of Green Tea Mega EGCG against electromagnetic radiation-induced oxidative stress in the hippocampus and striatum of rats.

    Science.gov (United States)

    Ahmed, Nawal A; Radwan, Nasr M; Aboul Ezz, Heba S; Salama, Noha A

    2017-01-01

    Electromagnetic radiation (EMR) of cellular phones may affect biological systems by increasing free radicals and changing the antioxidant defense systems of tissues, eventually leading to oxidative stress. Green tea has recently attracted significant attention due to its health benefits in a variety of disorders, ranging from cancer to weight loss. Thus, the aim of the present study was to investigate the effect of EMR (frequency 900 MHz modulated at 217 Hz, power density 0.02 mW/cm 2 , SAR 1.245 W/kg) on different oxidative stress parameters in the hippocampus and striatum of adult rats. This study also extends to evaluate the therapeutic effect of green tea mega EGCG on the previous parameters in animals exposed to EMR after and during EMR exposure. The experimental animals were divided into four groups: EMR-exposed animals, animals treated with green tea mega EGCG after 2 months of EMR exposure, animals treated with green tea mega EGCG during EMR exposure and control animals. EMR exposure resulted in oxidative stress in the hippocampus and striatum as evident from the disturbances in oxidant and antioxidant parameters. Co-administration of green tea mega EGCG at the beginning of EMR exposure for 2 and 3 months had more beneficial effect against EMR-induced oxidative stress than oral administration of green tea mega EGCG after 2 months of exposure. This recommends the use of green tea before any stressor to attenuate the state of oxidative stress and stimulate the antioxidant mechanism of the brain.

  12. Effect of Exercise Preconditioning on Memory Deficits and Neuronal Cell Death in the CA3 Pyramidal Cells of the Rat Hippocampus Following Transient Global Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    N Shamsaei

    2015-09-01

    Full Text Available Background & objectives: Brain ischemia leads to irreversible functional and structural damage in various regions of the brain, especially in the hippocampus. There is an evidence indicating the physical exercise has neuroprotective effects and may decrease the cerebral ischemia/ reperfusion injury in rats. The purpose of this study was the study of the effect of exercise preconditioning on memory deficits and neuronal cell death in CA3 pyramidal cells of the rat hippocampus following transient global ischemia.   Methods: 21 male rats weighing 260-300g were randomly selected and allocated into three groups (sham, ischemia and exercise+ischemia. The rats in exercise group were trained to run on a treadmill 5 days a week for 4 weeks. Ischemia induced by occlusion both common carotid arteries (CCA for 20 minutes. The passive avoidance memory test using a Shuttle box used to assess the impairment of memory. The amount of cell death was measured using cresyl violet staining method.   Results: The results showed that cerebral ischemia is associated with memory impairment, and physical activity before ischemia improves ischemia-induced memory impairments significantly (p<0.05. In addition, ischemia leads to cell death in hippocampal CA3 area neurons and exercise also reduces ischemia-induced cell death significantly (p<0.05.   Conclusion: This study showed that exercise, when is used as a preconditioning stimulant , has a neuroprotective effects against brain ischemia.

  13. Cancer preventive effects of vitamin E.

    Science.gov (United States)

    Wada, Sayori

    2012-01-01

    Vitamin E is well known as an antioxidant, with 8 natural isoforms, such as α-, bgr;-, γ- and δ-tocopherols and α-, β-, gamma;- and δ-tocotrienols. It has been suggested that both tocopherols and tocotrienols have anti-tumor effects due to the antioxidant effect. The results of several studies have indicated that the tocotrienols may have a stronger bioactivity than the tocopherols. Both types have shown antiproliferative, proapoptotic and cyclooxygenase-2- inhibiting effects in in vitro studies. Several animal studies have demonstrated that vitamin E has cancer-preventing effects. However, clinical trials have not shown similar results for the cancer prevention effect of tocopherol. Although the Linxian Trials demonstrated that the supplementation of β-carotene, α-tocopherol and selenium reduced cancer risk, the beneficial effects of α- tocopherol on prostate cancer disappeared after several years in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Vitamin E, especially tocotrienols, seems to be a potent agent for cancer prevention, however no large-scale clinical trial on the cancer prevention effect of tocotrienols has been conducted yet. Therefore it is expected that clinical trials overcoming the lower bioavailability of tocotrienols will be conducted, and it is urgently needed to assess the safety and the efficacy of the administration of the tocotrienols as a part of a cancer prevention regimen.

  14. Long-term effects of pre and post-ischemic exercise following global cerebral ischemia on astrocyte and microglia functions in hippocampus from Wistar rats.

    Science.gov (United States)

    Lovatel, Gisele Agustini; Bertoldi, Karine; Elsnerb, Viviane Rostirola; Piazza, Francele Valente; Basso, Carla Giovana; Moysés, Felipe Dos Santos; Worm, Paulo Valdeci; Netto, Carlos Alexandre; Marcuzzo, Simone; Siqueira, Ionara Rodrigues

    2014-10-31

    Persistent effects of pre- and postischemic exercise on glial cells activation after global cerebral ischemia remains poorly understood. Here, we investigated the effect of both pre and postischemic treadmill exercise protocols (20min/day during 2 weeks) on glial cells immunostaining in the hippocampus of Wistar rats submitted to global ischemia. A synergistic effect between ischemia and postischemic exercise on the astrocytic area was demonstrated. Postischemic exercise partially reversed the ischemia-induced increase on the area occupied by microglia, without any effect of pre-ischemic protocol. In conclusion, postischemic exercise distinctly modulates astrocyte and microglia immunostaining in the hippocampal dentate gyrus following global cerebral ischemia in Wistar rats. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Alterations in right posterior hippocampus in early blind individuals

    DEFF Research Database (Denmark)

    Chebat, Daniel-Robert; Chen, Jan-Kai; Schneider, Fabien

    2007-01-01

    This study compares hippocampal volumes of early blind and sex/age-matched sighted controls through volumetric and localization analyses. Early blind individuals showed a significantly smaller right posterior hippocampus compared with controls. No differences in total hippocampal volumes were found...... between groups and there were no within-group differences for left versus right hippocampus. Sex, age and total brain grey matter volume had no effect on hippocampal volumes. Although extensive navigational training results in structural enhancement of the hippocampus for the sighted, the reduction...... of the posterior hippocampus in early blind individuals suggests the implication of this region in visual spatial memory. Udgivelsesdato: 2007-Mar-5...

  16. Effects of electroacupuncture on ethanol-induced impairments of spatial learning and memory and Fos expression in the hippocampus in rats.

    Science.gov (United States)

    Lu, Bin; Ma, Zhao; Cheng, Fei; Zhao, Yan; Zhang, Xin; Mao, Huijuan; Shen, Xueyong; Liu, Sheng

    2014-07-25

    It is well established that alcohol impairs spatial learning and memory. Here, we investigated the effects of electroacupuncture (EA) at ST36 or nonacupoint on ethanol-induced learning and memory impairment and the expression of Fos in the hippocampus. Ethanol (5g/kg) was administered intragastrically once a day for 5 consecutive days; 2Hz EA was administered immediately after ethanol exposure. After a 2-day ethanol abstinence, for 6 consecutive days, the rats were submitted to Morris water maze training. Probe trials were performed on 1 day after the final training session. We also applied immunohistochemistry to detect Fos-positive nuclei in the hippocampus. We found that 5-day ethanol exposure markedly decreased spatial learning and memory abilities in the Morris water maze task as indicated by escape latency and time in the target quadrant. EA treatment shortened the time of reaching platform and increased times traveled in the target quadrant (Plearning and memory, which may be involved in the hippocampal CA1 area. EA treatment may provide a novel nonpharmacological strategy for ethanol-induced learning and memory impairment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. [Effect of rapid eye movement sleep deprivation on anxiety behavior and hippocampus NO level: different responses of adolescent and adult C57BL/6J mice].

    Science.gov (United States)

    Huang, Xin-Yan; Chen, Tian-Bin; Hao, Yan-Li; Zhang, Bin

    2015-10-01

    To explore the difference between adolescent and adult C57BL/6J mice in response to rapid eye movement sleep (REMS) deprivation in terms of anxiety behavior and hippocampal NO level. Both adolescent and adult C57BL/6J mice were divided into normal control (NC) group, wide platform (WP) group, and 24-hour REMS deprivation group, each group consisting of 15 mice. REMS deprivation models were established using a small platform in water tank, and the elevated plus maze test was used to examine anxiety behavior of the mice. After behavioral tests, the mice were sacrificed to examine hippocampal NO levels using enzyme-linked immunosorbent assay, and hippocampal nNOS protein expression was detected with Western blotting. The adolescent C57BL/6J mice showed no obvious differences in anxiety behaviors between the 3 groups, but NO level and nNOS expression in the hippocampus was significantly higher in REMSD group than in NC and WP groups (Pdeprivation produces different effects on anxiety-related behaviors between adolescent and adult mice possibly in relation to their different responses in terms of NO levels and nNOS expression in the hippocampus.

  18. The effects of prenatal stress on expression of CaMK-II and L-Ca2+ channel in offspring hippocampus.

    Science.gov (United States)

    Cai, Qing; Zhang, Boli; Huang, Shuyun; Wang, Tao; Zhou, Tao

    2011-08-01

    The purpose of the present study was to characterize the expressions of phosphorylated Ca(2+)/calmodulin-dependent protein kinase II (p-CaMK-II), total CaMK-II, and L-type Ca(2+) channel in offspring hippocampus that was induced by prenatal restraint stress. Pregnant rats were divided into two groups: the control group and the prenatal stress (PNS) group. Pregnant rats in the PNS group were exposed to restraint stress on day 14-20 of pregnancy three times daily for 45 min. Adult offspring rats were used in this study. The results demonstrated that prenatal restraint stress induced a significant increase in the expression of p-CaMK-II, total CaMK-II, and L-Ca(2+) channel by western blot analysis in offspring hippocampus. The immunohistochemistry results revealed that PNS increased the expressions of CaMK-II and L-Ca(2+) channel in the hippocampal CA3 of offspring rats. These data suggest that PNS can have long-term neuronal effects within hippocampal structure involved in the feedback mechanisms of the hypothalamo-pituitary-adrenal axis.

  19. Effects of Ethanol on the Expression Level of Various BDNF mRNA Isoforms and Their Encoded Protein in the Hippocampus of Adult and Embryonic Rats

    Directory of Open Access Journals (Sweden)

    Shahla Shojaei

    2015-12-01

    Full Text Available We aimed to compare the effects of oral ethanol (Eth alone or combined with the phytoestrogen resveratrol (Rsv on the expression of various brain-derived neurotrophic factor (BDNF transcripts and the encoded protein pro-BDNF in the hippocampus of pregnant and embryonic rats. A low (0.25 g/kg body weight (BW/day dose of Eth produced an increase in the expression of BDNF exons I, III and IV and a decrease in that of the exon IX in embryos, but failed to affect BDNF transcript and pro-BDNF protein expression in adults. However, co-administration of Eth 0.25 g/kg·BW/day and Rsv led to increased expression of BDNF exons I, III and IV and to a small but significant increase in the level of pro-BDNF protein in maternal rats. A high (2.5 g/kg·BW/day dose of Eth increased the expression of BDNF exons III and IV in embryos, but it decreased the expression of exon IX containing BDNF mRNAs in the maternal rats. While the high dose of Eth alone reduced the level of pro-BDNF in adults, it failed to change the levels of pro-BDNF in embryos. Eth differentially affects the expression pattern of BDNF transcripts and levels of pro-BDNF in the hippocampus of both adult and embryonic rats.

  20. The effect of high energy (HZE) particle radiation (Ar-40) on aging parameters of mouse hippocampus and retina

    Science.gov (United States)

    Philpott, D. E.; Kato, K.; Corbett, R.; Stevenson, J.; Black, S.; Sapp, W.; Miquel, J.; Lindseth, K. A.; Benton, E. V.

    1985-01-01

    Eight month old C57BL6 mice were exposed (head only) to 0.5 rad or 50 rads of Argon particles at the Lawrence Berkeley Radiation Facility, CA. Neuromotor performance was assessed monthly for six months beginning twelve weeks post-irradiation using a 'string test'. The decline in motor performance was dose-related and none of the animals was able to complete the task after four months of testing. Morphological changes were monitored six and twelve months post-irradiation by light and electron microscopy. The synaptic density in the CA-1 area of the hippocampus decreased six and twelve months after irradiation. The decrease after twelve months was less than after six months. The width of the outer nuclear layer (ONL) of the retina increased with increasing dose. The number of blood vessels between the ONL and the ganglion layer decreased twelve months after irradiation and this area did not show significant accumulation of age pigment.

  1. The effect of chronic ozone exposure on the activation of endoplasmic reticulum stress and apoptosis in rat hippocampus

    Directory of Open Access Journals (Sweden)

    Erika Rodríguez-Martínez

    2016-10-01

    Full Text Available The chronic exposure to low doses of ozone, like in environmental pollution, leads to a state of oxidative stress, which has been proposed to contribute to neurodegenerative disorders, including Alzheimer's disease. It induces an increase of calcium in the endoplasmic reticulum (ER, which produces ER stress. On the other hand, different studies show that, in diseases such as Alzheimer’s, there exist disturbances in protein folding where ER plays an important role. The objective of this study was to evaluate the state of chronic oxidative stress on ER stress and its relationship with apoptotic death in the hippocampus of rats exposed to low doses of ozone. We used 108 male Wistar rats randomly divided into five groups. The groups received one of the following treatments: 1 Control (air, 2 Ozone (O3 7 days, 3 O3 15 days, 4 O3 30 days, 5 O3 60 days, and 6 O3 90 days. Two hours after each treatment, the animals were sacrificed and the hippocampus was extracted. Afterwards, the tissue was processed for western blot and immunohistochemistry using the following antibodies: ATF6, GRP8 and caspase 12. It was also performed TUNEL assay and electronic microscopy. Our results show an increase in ATF6, GRP78 and caspase 12 as well as ER ultrastructural alterations and an increase of TUNEL positive cells after 60 and 90 days of exposure to ozone. With the obtained results, we can conclude that oxidative stress induced by chronic exposure to low doses of ozone leads to ER stress. ER stress activates ATF6 inducing the increase of GRP78 in the cytoplasm, which leads to the increase in the nuclear translocation of ATF6. Finally, the translocation creates a vicious cycle that, together with the activation of the cascade for apoptotic cell death, contributes to the maintenance of ER stress. These events potentially contribute in the neurodegeneration processes in diseases like Alzheimer’s Disease.

  2. Clearance of fear memory from the hippocampus through neurogenesis by omega-3 fatty acids: a novel preventive strategy for posttraumatic stress disorder?

    Directory of Open Access Journals (Sweden)

    Matsuoka Yutaka

    2011-02-01

    Full Text Available Abstract Not only has accidental injury been shown to account for a significant health burden on all populations, regardless of age, sex and geographic region, but patients with accidental injury frequently present with the psychiatric condition of posttraumatic stress disorder (PTSD. Prevention of accident-related PTSD thus represents a potentially important goal. Physicians in the field of psychosomatic medicine and critical care medicine have the opportunity to see injured patients in the immediate aftermath of an accident. This article first briefly reviews the prevalence and associated factors of accident-related PTSD, then focuses on a conceptual model of fear memory and proposes a new, rationally hypothesized translational preventive intervention for PTSD through promoting hippocampal neurogenesis by omega-3 fatty acid supplementation. The results of an open-label pilot trial of injured patients admitted to the intensive care unit suggest that omega-3 fatty acid supplementation immediately after accidental injury can reduce subsequent PTSD symptoms.

  3. Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus.

    Science.gov (United States)

    Dale, Elena; Zhang, Hong; Leiser, Steven C; Xiao, Yixin; Lu, Dunguo; Yang, Charles R; Plath, Niels; Sanchez, Connie

    2014-10-01

    Vortioxetine, a novel antidepressant with multimodal action, is a serotonin (5-HT)3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist and a 5-HT transporter (SERT) inhibitor. Vortioxetine has been shown to improve cognitive performance in several preclinical rat models and in patients with major depressive disorder. Here we investigated the mechanistic basis for these effects by studying the effect of vortioxetine on synaptic transmission, long-term potentiation (LTP), a cellular correlate of learning and memory, and theta oscillations in the rat hippocampus and frontal cortex. Vortioxetine was found to prevent the 5-HT-induced increase in inhibitory post-synaptic potentials recorded from CA1 pyramidal cells, most likely by 5-HT3 receptor antagonism. Vortioxetine also enhanced LTP in the CA1 region of the hippocampus. Finally, vortioxetine increased fronto-cortical theta power during active wake in whole animal electroencephalographic recordings. In comparison, the selective SERT inhibitor escitalopram showed no effect on any of these measures. Taken together, our results indicate that vortioxetine can increase pyramidal cell output, which leads to enhanced synaptic plasticity in the hippocampus. Given the central role of the hippocampus in cognition, these findings may provide a cellular correlate to the observed preclinical and clinical cognition-enhancing effects of vortioxetine. © The Author(s) 2014.

  4. The Effect of Rosa Damascena Extract on Expression of Neurotrophic Factors in the CA1 Neurons of Adult Rat Hippocampus Following Ischemia

    Directory of Open Access Journals (Sweden)

    Seyedeh Farzaneh Moniri

    2018-01-01

    Full Text Available Ischemic stroke is an important cause of death and disability in the world. Brain ischemia causes damage to brain cell, and among brain neurons, pyramidal neurons of the hippocampal CA1 region are more susceptive to ischemic injury. Recent findings suggest that neurotrophic factors protect against ischemic cell death. A dietary component of Rosa damascene extract possibly is associated with expression of neurotrophic factors mRNA following ischemia, so it can have therapeutic effect on cerebral ischemia. The present study attempts to evaluate the neuroprotective effect of Rosa damascene extract on adult rat hippocampal neurons following ischemic brain injury. Forty-eight adult male Wistar rats (weighing 250±20 gr and ages 10-12 weeks used in this study, animals randomly were divided into 6 groups including Control, ischemia/ reperfusion (IR, vehicle and three treated groups (IR+0.5, 1, 2 mg/ml extract. Global ischemia was induced by bilateral common carotid arteries occlusion for 20 minutes. The treatment was done by different doses of Rosa damascena extract for 30 days. After 30 days cell death and gene expression in neurons of the CA1 region of the hippocampus were evaluated by Nissl staining and real time PCR assay. We found a significant decrease in NGF, BDNF and NT3 mRNA expression in neurons of CA1 region of the hippocampus in ischemia group compared to control group (P<0.0001. Our results also revealed that the number of dark neurons significantly increases in ischemia group compared to control group (P<0.0001. Following treatment with Rosa damascene extract reduced the number of dark neurons that was associated with NGF, NT3, and BDNF mRNA expression. All doses level had positive effects, but the most effective dose of Rosa damascena extract was 1 mg/ml. Our results suggest that neuroprotective activity of Rosa damascena can enhance hippocampal CA1 neuronal survival after global ischemia.

  5. Effects of acute and sustained administration of vortioxetine on the serotonin system in the hippocampus: electrophysiological studies in the rat brain.

    Science.gov (United States)

    El Mansari, Mostafa; Lecours, Maurice; Blier, Pierre

    2015-07-01

    Vortioxetine is a novel multimodal antidepressant that is a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist, an inhibitor of the serotonin (5-HT) transporter, and a 5-HT1D, 5-HT3, and 5-HT7 receptor antagonist in vitro. In vivo studies have shown that vortioxetine enhances levels of 5-HT and desensitizes 5-HT1A autoreceptors. The aim of the present study was to investigate the effects of acute and long-term administration of vortioxetine on the terminal 5-HT1B receptor and the tonic activation of 5-HT1A receptor in the rat hippocampus. These receptors were assessed following vortioxetine administration acutely or subcutaneously using minipumps for 14 days. These studies were carried out using in vivo electrophysiological recording, microiontophoresis, and stimulation of the ascending 5-HT fibers. Vortioxetine enhanced the inhibitory effect of the stimulation of the 5-HT bundle at a high, but not low frequency and reversed the inhibitory effect of the 5-HT1B receptor agonist CP 94253. These results indicate that this compound acted as a 5-HT1B receptor partial agonist. Vortioxetine inhibited 5-HT reuptake but did not dampen the sensitivity of postsynaptic 5-HT1A receptors on pyramidal neurons. Long-term administration of vortioxetine and escitalopram (both at 5 mg/kg/day) induced an increase of tonic activation of the 5-HT1A receptors in CA3 pyramidal neurons, resulting in an increase in 5-HT transmission. In addition, vortioxetine decreased the function of terminal 5-HT1B autoreceptor following its sustained administration. Desensitization of 5-HT1B autoreceptor and an increase of tonic activation of 5-HT1A receptors in the hippocampus may contribute to the antidepressant effect of vortioxetine.

  6. The Effect of Rosa Damascena Extract on Expression of Neurotrophic Factors in the CA1 Neurons of Adult Rat Hippocampus Following Ischemia.

    Science.gov (United States)

    Moniri, Seyedeh Farzaneh; Hedayatpour, Azim; Hassanzadeh, Gholamreza; Vazirian, Mahdi; Karimian, Morteza; Belaran, Maryam; Ejtemaie Mehr, Shahram; Akbari, Mohamad

    2017-12-01

    Ischemic stroke is an important cause of death and disability in the world. Brain ischemia causes damage to brain cell, and among brain neurons, pyramidal neurons of the hippocampal CA1 region are more susceptive to ischemic injury. Recent findings suggest that neurotrophic factors protect against ischemic cell death. A dietary component of Rosa damascene extract possibly is associated with expression of neurotrophic factors mRNA following ischemia, so it can have therapeutic effect on cerebral ischemia. The present study attempts to evaluate the neuroprotective effect of Rosa damascene extract on adult rat hippocampal neurons following ischemic brain injury. Forty-eight adult male Wistar rats (weighing 250±20 gr and ages 10-12 weeks) used in this study, animals randomly were divided into 6 groups including Control, ischemia/ reperfusion (IR), vehicle and three treated groups (IR+0.5, 1, 2 mg/ml extract). Global ischemia was induced by bilateral common carotid arteries occlusion for 20 minutes. The treatment was done by different doses of Rosa damascena extract for 30 days. After 30 days cell death and gene expression in neurons of the CA1 region of the hippocampus were evaluated by Nissl staining and real time PCR assay. We found a significant decrease in NGF, BDNF and NT3 mRNA expression in neurons of CA1 region of the hippocampus in ischemia group compared to control group (Pextract reduced the number of dark neurons that was associated with NGF, NT3, and BDNF mRNA expression. All doses level had positive effects, but the most effective dose of Rosa damascena extract was 1 mg/ml. Our results suggest that neuroprotective activity of Rosa damascena can enhance hippocampal CA1 neuronal survival after global ischemia.

  7. Cocaine- or stress-induced metaplasticity of LTP in the dorsal and ventral hippocampus.

    Science.gov (United States)

    Keralapurath, Madhusudhanan M; Clark, Jason K; Hammond, Sherri; Wagner, John J

    2014-05-01

    Despite the well documented role of the hippocampus in various modes of drug reinstatement behavior, the persisting effects of in vivo cocaine exposure on hippocampal synaptic plasticity are not sufficiently understood. In this report we investigated the effects of cocaine conditioning on long-term potentiation (LTP) in the CA1 region of hippocampus along its septotemporal axis. Male Sprague-Dawley rats experienced a behavioral protocol, in which locomotor activity was monitored in response to various conditioning treatments. LTP was measured in ex vivo slice preparations taken 1-2 weeks after the last behavioral session from the ventral (vH) and dorsal (dH) sectors of hippocampus. Unexpectedly, experiencing the minor intermittent stimuli of the behavioral protocol caused stress-induced metaplastic changes in both vH (increased LTP) and dH (decreased LTP) in the saline conditioned rats relative to behaviorally naïve controls. These stress effects in the vH and dH were blocked by conditioning with either mineralocorticoid (spironolactone) or glucocorticoid (mifepristone) antagonists, respectively. Stress-induced metaplasticity in the vH was also prevented by prior administration of the kappa opioid antagonist nor-binaltorphimine. Cocaine conditioning induced locomotor sensitization and significantly increased LTP in the vH without causing significant change in LTP in the dH. Cocaine-induced metaplasticity in the vH was prevented by co-administration of the dopamine D2-like antagonist eticlopride during cocaine conditioning, but not by co-administration of the D1/5 antagonist SCH 23390. Our results suggest that the functional connectivity of hippocampus is altered by metaplastic triggers such as exposure to drugs of abuse and/or stressors, thereby shifting the efferent output of hippocampus from dH (cortical) toward vH (limbic) influenced circuits. Copyright © 2014 Wiley Periodicals, Inc.

  8. Developmental approach to prevent adolescent suicides: research pathways to effective upstream preventive interventions

    National Research Council Canada - National Science Library

    Wyman, Peter A

    2014-01-01

    .... Prevention trial results show that current universal prevention programs for children and young adolescents are effective in reducing adolescent emotional and behavioral problems that are risk...

  9. Effects of propofol, ginsenoside Rg-1, protein phosphatase-2a, and lithium on the learning and memory in rats and the content of glutamic acid in hippocampus after the electroconvulsive therapy.

    Science.gov (United States)

    Liu, Chao; Zhang, Xue-Ning; Liu, Dong; Min, Su

    2014-06-01

    To explore and compare the effects of propofol, ginsenoside Rg-1, protein phosphatae-2A, and lithium on the learning and memory and the concentration of glutamic acid in hippocampus after the electroconvulsive therapy (ECT) in the model of depressed rats induced after the removal of olfactory bulb. The depressed rats were randomized into ECT intervention (two levels:no disposition and a course of electroconvulsive shock) and drug intervention (five levels:microinjection of saline injection, propofol, ginsenoside Rg-1, protein phosphatae-2A, and lithium, 20 g/L). Learning and memory were evaluated using the Morris water maze test within 24 h after the course of ECT. Glutamate contents in the hippocampus of rats were examined using high-performance liquid chromatography. Both propofol alone and ECT alone induced the impairment of learning and memory in depressed rats, but their combination alleviated the such impairment caused by ECT. Ginsenoside Rg-1, protein phosphatae-2A ,and lithium had no obvious effect on the leaning and improved the learning and memory when in combination with ECT. There was a synergic effect between ECT intervention and drug intervention. ECT remarkably increased the glutamate content in the hippocampus of depressed rats, which could be reduced by both propofol and ginsenoside Rg-1. Protein phosphatae-2A and lithium did not affect glutamate content in the hippocampus of depressed rats before and after ECT. ECT can increase the content of glutamate in hippocampus and thus cause the impairment of learning and memory in depressed rats. Propofol and ginsenoside Rg-1 can ameliorate the impairment by reducing the content of glutamate in hippocampus. Protein phosphatae-2A and lithium may also improve the learning and memory in depressed rats.

  10. Improved statistical power with a sparse shape model in detecting an aging effect in the hippocampus and amygdala

    Science.gov (United States)

    Chung, Moo K.; Kim, Seung-Goo; Schaefer, Stacey M.; van Reekum, Carien M.; Peschke-Schmitz, Lara; Sutterer, Matthew J.; Davidson, Richard J.

    2014-03-01

    The sparse regression framework has been widely used in medical image processing and analysis. However, it has been rarely used in anatomical studies. We present a sparse shape modeling framework using the Laplace- Beltrami (LB) eigenfunctions of the underlying shape and show its improvement of statistical power. Tradition- ally, the LB-eigenfunctions are used as a basis for intrinsically representing surface shapes as a form of Fourier descriptors. To reduce high frequency noise, only the first few terms are used in the expansion and higher frequency terms are simply thrown away. However, some lower frequency terms may not necessarily contribute significantly in reconstructing the surfaces. Motivated by this idea, we present a LB-based method to filter out only the significant eigenfunctions by imposing a sparse penalty. For dense anatomical data such as deformation fields on a surface mesh, the sparse regression behaves like a smoothing process, which will reduce the error of incorrectly detecting false negatives. Hence the statistical power improves. The sparse shape model is then applied in investigating the influence of age on amygdala and hippocampus shapes in the normal population. The advantage of the LB sparse framework is demonstrated by showing the increased statistical power.

  11. Effects of intermittent aerobic training on passive avoidance test (shuttle box) and stress markers in the dorsal hippocampus of wistar rats exposed to administration of homocysteine.

    Science.gov (United States)

    Hosseinzadeh, Somayeh; Dabidi Roshan, Valiollah; Pourasghar, Mehdi

    2013-01-01

    Elevated amino acid homocysteine (Hcy) levels and insufficient physical activity are the risk factors in Alzheimer disease (AD) development. The effect of intermittent aerobic training on memory retention test and Thiobarbituric Acid Reactive Substances (TBARS) and superoxide dismutase (SOD) levels in the dorsal hippocampus of rats which were stimulated with Hcy is investigated. In order to determine the dose at which using Shuttle Box Test recognizes degenerative changes and/or memory impairment, 40 rats were injected by different dosages of Hcy to the dorsal hippocampus. It was observed that the required Hcy dose is 0.6 M. Then 44 rats were divided into four groups including training and control groups at 4 weeks of aerobic exercise in training and control groups at 8 weeks. To determine the effect of homocysteine on the memory impairment, Shuttle Box Test was used on treadmill (5 sessions/week, 12-18 m/min and 10-58.5 min). Hcy administration caused memory impairment and significant increase in TBARS. Significant decrease in TBARS level was noted after 8 weeks of aerobic exercise, but not after just 4 weeks of exercise compared with control group. In addition, performing 8 weeks of aerobic training led to significantly increased superoxide dismutase (SOD) level and the time of avoidance learning test. Hyperhomocysteinemia caused learning and memory deficits probably by generating reactive oxygen species (ROS) and the present study showed that regular moderate intensity intermittent exercise may reverse this process and exercise is recommended as a strategy to improve symptoms of senile neurodegenerative disease . None.

  12. Negative effects of ultrafine particle exposure during forced exercise on the expression of Brain-Derived Neurotrophic Factor in the hippocampus of rats.

    Science.gov (United States)

    Bos, I; De Boever, P; Int Panis, L; Sarre, S; Meeusen, R

    2012-10-25

    Exercise improves cognitive function, and Brain-Derived Neurotrophic Factor (BDNF) plays a key role in this process. We recently reported that particulate matter (PM) exposure negatively contributed to the exercise-induced increase in human serum BDNF concentration. Furthermore, PM exposure is associated with neuroinflammation and cognitive decline. The aim of this study was to investigate the effect of exposure to ultrafine particles (UFP) during a single bout of forced exercise on the expression of inflammatory (IL1α, IL1β, TNF, IL6, NOS2, NOS3) and oxidative stress (NFE2L2)-related genes, as well as BDNF in the brain of rats. Four groups (n=6/group) of Wistar rats were exposed for 90 min to one of the following exposure regimes: UFP+exercise, UFP+rest, ambient air+exercise, ambient air+rest (control). Hippocampus, olfactory bulb and prefrontal cortex were collected 24h after exposure. Gene expression changes were analyzed with real-time PCR. In the condition ambient air+exercise, hippocampal expression of BDNF and NFE2L2 was up-regulated, while the expression of IL1α and NOS3 in the prefrontal cortex and IL1α in the olfactory bulb was down-regulated compared to the control. In contrast, gene expression in the condition UFP+exercise did not differ from the control. In the condition UFP+rest, hippocampal expression of NFE2L2 was down-regulated and there was a trend toward down-regulation of BDNF expression compared to the control. This study shows a negative effect of UFP exposure on the exercise-induced up-regulation of BDNF gene expression in the hippocampus of rats. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  14. Neuropharmacological effects of lipoic acid and ubiquinone on δ-aminolevulinic dehydratase, Na(+) , K(+) -ATPase, and Mg(2+) -ATPase activities in rat hippocampus after pilocarpine-induced seizures.

    Science.gov (United States)

    de Freitas, Rivelilson Mendes; Feng, Dejiang; Jordán, Joaquín

    2011-04-01

    In this study, we investigated the effects of lipoic acid (LA) in the hippocampus oxidative stress caused by pilocarpine-induced seizures in adult rats. Wistar rats were treated with 0.9% saline (i.p., control group), LA (10mg/kg, i.p., LA group), ubiquinone [20mg/kg, i.p., ubiquinone (UQ) group], pilocarpine (400mg/kg, i.p., P400 group), and the association of LA (10mg/kg, i.p.) plus pilocarpine (400mg/kg, i.p.) or UQ (20mg/kg, i.p.) plus pilocarpine (400mg/kg, i.p.), 30min before of administration of P400 (LA plus P400 group and UQ plus P400 group, respectively). After the treatments, all groups were observed for 1h. The enzyme activities (δ-aminolevulinic dehydratase (δ-ALA-D), Mg(2+) -ATPase, and Na(+) , K(+) -ATPase) were measured using spectrophotometric methods, and the results compared to values obtained from saline and pilocarpine-treated animals. Protective effects of LA and UQ were also evaluated on the same parameters. We reported here for the first time that Na(+) , K(+) -ATPase and δ-ALA-D activities inhibition and Mg(2+) -ATPase stimulation in the pilocarpine model are probably attributed to the oxidative stress caused by seizures in the rat hippocampus. The addition of the antioxidants LA and UQ may reverses the previously mentioned Na(+) , K(+) -ATPase and δ-ALA-D inhibitions and Mg(2+) -ATPase stimulation. The oxidative stress plays an important signaling role in pilocarpine-induced seizures, and antioxidant drugs might be considered as therapeutical tools in this pathology. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

  15. Maximum potential preventive effect of hip protectors

    NARCIS (Netherlands)

    van Schoor, N.M.; Smit, J.H.; Bouter, L.M.; Veenings, B.; Asma, G.B.; Lips, P.T.A.M.

    2007-01-01

    OBJECTIVES: To estimate the maximum potential preventive effect of hip protectors in older persons living in the community or homes for the elderly. DESIGN: Observational cohort study. SETTING: Emergency departments in the Netherlands. PARTICIPANTS: Hip fracture patients aged 70 and older who

  16. Effectiveness of programs to prevent school bullying

    NARCIS (Netherlands)

    Baldry, A.C.; Farrington, D.P.

    2007-01-01

    Sixteen major evaluations of programs to prevent school bullying, conducted in 11 different countries, are reviewed in detail. Of these 16 evaluations, 8 produced desirable results, 2 produced mixed results, 4 produced small or negligible effects, and 2 produced undesirable results. These varying

  17. The cancer preventive effects of edible mushrooms.

    Science.gov (United States)

    Xu, Tongtong; Beelman, Robert B; Lambert, Joshua D

    2012-12-01

    An increasing body of scientific literature suggests that dietary components may exert cancer preventive effects. Tea, soy, cruciferous vegetables and other foods have been investigated for their cancer preventive potential. Some non-edible mushrooms like Reishi (Ganoderma lucidum) have a history use, both alone and in conjunction with standard therapies, for the treatment of various diseases including cancer in some cultures. They have shown efficacy in a number of scientific studies. By comparison, the potential cancer preventive effects of edible mushrooms have been less well-studied. With similar content of putative effective anticancer compounds such as polysaccharides, proteoglycans, steroids, etc., one might predict that edible mushrooms would also demonstrate anticancer and cancer preventive activity. In this review, available data for five commonly-consumed edible mushrooms: button mushrooms (Agaricus bisporus), A. blazei, oyster mushrooms (Pleurotus ostreatus), shiitake mushrooms (Lentinus edodes), and maitake (Grifola frondosa) mushrooms is discussed. The results of animal model and human intervention studies, as well as supporting in vitro mechanistic studies are critically evaluated. Weaknesses in the current data and topics for future work are highlighted.

  18. Effects of high-altitude environment on cognitive function and ultrastructure in CA1 region of hippocampus of rats after sleep deprivation

    Directory of Open Access Journals (Sweden)

    Jiang-hua SI

    2014-04-01

    Full Text Available Objective To investigate the effects of high-altitude environment on cognitive function and ultrastructure in CA1 region of the hippocampus of Wistar rats in sleep deprivation (SD.  Methods SD was induced in Wistar rats by employing "flower pot" technique. Sixty-four rats were randomly divided into 2 groups: Lanzhou group (at an altitude of 1520 m and Kekexili group (at an altitude of 4767 m, and each group was further divided into 4 subgroups according to the time of SD (0, 1, 3 and 5 d. The behaviors of rats were studied by Morris water maze test at given time points. The ultrastructure of hippocampal neurons was observed by transmission electron microscope (TEM.  Results 1 Compared with Lanzhou group, rat behavior of Kekexili group presented excitement-irritation-suppression changes with the extension of SD time, but the extent was weakened gradually, and time of sleepiness increased obviously. 2 Compared with Lanzhou group, neurons in CA1 region of hippocampus showed enlarged cell body, disappeared nuclear membrane, shrunken nuclei and decreased organelle. End-feet of glia cells sticking to capillaries swelled and ruptured, and the typical synaptic structure disappeared. 3 Morris water maze test: as compared with Lanzhou group, the escape latency of Kekexili group prolonged (P < 0.05, for all, the ability of distance exploration increased (P < 0.05, for all, and the times across plot decreased (P < 0.05, for all in 1, 3 and 5 d of SD.  Conclusions High-altitude environment may significantly influence the cognitive function of rats in SD, and there was close correlation between the cognitive disorders and the changes in the ultrastructure of hippocampal CA1 region. doi: 10.3969/j.issn.1672-6731.2014.04.012

  19. Electroconvulsive stimulations prevent chronic stress-induced increases in L-type calcium channel mRNAs in the hippocampus and basolateral amygdala

    DEFF Research Database (Denmark)

    Maigaard, Katrine; Pedersen, Ida Hageman; Jørgensen, Anders

    2012-01-01

    in the brain. We find that stress tended to upregulate Ca(v)1.2 and Ca(v)1.3 channels in a brain region specific manner, while ECS tended to normalise this effect. This was more pronounced for Ca(v)1.2 channels, where stress clearly increased expression in both the basolateral amygdala, dentate gyrus and CA3...

  20. Functional compensation of increasing memory encoding demands in the hippocampus.

    Science.gov (United States)

    Ulrich, Martin; Jonas, Christina; Grön, Georg

    2010-01-06

    The hippocampus is well known to contribute to episodic memory encoding. Here we used functional magnetic resonance imaging to investigate the hippocampal response to exponentially varying encoding demands while forming associations between faces and names. We found that only the left hippocampus exhibited a stepped modulation of neuronal activity, which was furthermore correlated with individual memory performance. The right hippocampus, in contrast, showed a constant strong engagement throughout all difficulty levels. We hypothesize that the left hippocampus functionally compensated an overload of right hippocampal resources in an attempt to prevent memory decline. This explanation could help reconcile controversies in the debate of material-specific (i.e. verbal vs. nonverbal) lateralization of hippocampal activation.

  1. Prevention

    Science.gov (United States)

    Kerry Britton; Barbara Illman; Gary Man

    2010-01-01

    Prevention is considered the most cost-effective element of the Forest Service Invasive Species Strategy (USDA Forest Service 2004). What makes prevention difficult is the desire to maximize free trade and the resulting benefits to society while, at the same time, protecting natural resources. The role of science is to first identify which commodities pose an...

  2. Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

    National Research Council Canada - National Science Library

    Kutlu, Munir Gunes; Gould, Thomas J

    2016-01-01

    .... In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine...

  3. Andrographolide Stimulates Neurogenesis in the Adult Hippocampus

    Directory of Open Access Journals (Sweden)

    Lorena Varela-Nallar

    2015-01-01

    Full Text Available Andrographolide (ANDRO is a labdane diterpenoid component of Andrographis paniculata widely used for its anti-inflammatory properties. We have recently determined that ANDRO is a competitive inhibitor of glycogen synthase kinase-3β (GSK-3β, a key enzyme of the Wnt/β-catenin signaling cascade. Since this signaling pathway regulates neurogenesis in the adult hippocampus, we evaluated whether ANDRO stimulates this process. Treatment with ANDRO increased neural progenitor cell proliferation and the number of immature neurons in the hippocampus of 2- and 10-month-old mice compared to age-matched control mice. Moreover, ANDRO stimulated neurogenesis increasing the number of newborn dentate granule neurons. Also, the effect of ANDRO was evaluated in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer’s disease. In these mice, ANDRO increased cell proliferation and the density of immature neurons in the dentate gyrus. Concomitantly with the increase in neurogenesis, ANDRO induced the activation of the Wnt signaling pathway in the hippocampus of wild-type and APPswe/PS1ΔE9 mice determined by increased levels of β-catenin, the inactive form of GSK-3β, and NeuroD1, a Wnt target gene involved in neurogenesis. Our findings indicate that ANDRO stimulates neurogenesis in the adult hippocampus suggesting that this drug could be used as a therapy in diseases in which neurogenesis is affected.

  4. Comparison of the Effects of Adenosine A1 Receptors Activity in CA1 Region of the Hippocampus on Entorhinal Cortex and Amygdala Kindled Seizures in Rats

    Directory of Open Access Journals (Sweden)

    A. Heidarianpour

    2008-10-01

    Full Text Available Introduction & Objective: In the CNS, adenosine is known to suppress repetitive neuronal Firing, suggesting a role as an endogenous modifier of seizures. Indeed, intracerebral adenosine concentrations rise acutely during seizure activity and are thought to be responsible for terminating seizures and establishing a period of post-ictal refractoriness. However, it is unclear whether this suppression results from a general depression of brain excitability or through action on particular sites critical for the control of after discharge generation and/or seizure development and propagation. In this regard, comparison of the effects of adenosine A1 receptors of CA1 (region of the ‎hippocampus on entorhinal cortex and amygdala kindled seizures was ‎investigated in this study. Materials & Methods: In this experimental study, Animals were kindled by daily electrical stimulation of amygdale (group A or entorhinal cortex (group B. In the fully kindled animals, N6-‎cyclohexyladenosine (CHA;1 and 10 M; a selective adenosine A1 receptor ‎agonist and 1,3-dimethyl-8-cyclohexylxanthine(CPT;1 ‎µ‎M; a selective ‎adenosine A1 receptors antagonist were microinfused bilaterally into the CA1 ‎region of hippocampus (1l/2min and animals were stimulated at 5 and 15 minutes after drug ‎injection. All animals were received artificial cerebrospinal fluid, 24 h before ‎each drug injection and this result were used as control. Results: The seizure parameters were measured at 5 and 15min post injection. Obtained data showed that CHA at concentrations of 10 ‎µ‎M reduced ‎entorhinal cortex and amygdala after discharge and stage5 seizure durations and ‎increased stage4 latency. CHA at concentration 1‎µ‎M significantly alters ‎seizure parameters of group A but not effect on group B. Intrahippocampal (CA1 region pretreatment of CPT (1 ‎µ‎M before CHA abolished the effects of CHA on seizure parameters.Conclusion: It ‎may be

  5. Selection Effects and Prevention Program Outcomes

    Science.gov (United States)

    Hill, Laura G.; Rosenman, Robert; Tennekoon, Vidhura; Mandal, Bidisha

    2013-01-01

    A primary goal of the paper is to provide an example of an evaluation design and analytic method that can be used to strengthen causal inference in nonexperimental prevention research. We used this method in a nonexperimental multisite study to evaluate short-term outcomes of a preventive intervention, and we accounted for effects of two types of selection bias: self-selection into the program and differential dropout. To provide context for our analytic approach, we present an overview of the counterfactual model (also known as Rubin’s causal model or the potential outcomes model) and several methods derived from that model, including propensity score matching, the Heckman two-step approach, and full information maximum likelihood based on a bivariate probit model and its trivariate generalization. We provide an example using evaluation data from a community-based family intervention and a nonexperimental control group constructed from the Washington state biennial Healthy Youth risk behavior survey data (HYS) (HYS n = 68,846; intervention n = 1502). We identified significant effects of participant, program, and community attributes in self-selection into the program and program completion. Identification of specific selection effects is useful for developing recruitment and retention strategies, and failure to identify selection may lead to inaccurate estimation of outcomes and their public health impact. Counterfactual models allow us to evaluate interventions in uncontrolled settings and still maintain some confidence in the internal validity of our inferences; their application holds great promise for the field of prevention science as we scale up to community dissemination of preventive interventions. PMID:23417667

  6. Morphine-induced conditioned place preference and the alterations of p-ERK, p-CREB and c-fos levels in hypothalamus and hippocampus: the effects of physical stress.

    Science.gov (United States)

    Pahlevani, P; Fatahi, Z; Moradi, M; Haghparast, A

    2014-12-08

    The hypothalamus and hippocampus are important areas involved in stress responses and reward processing. In addition, ERK/CREB pathway plays a critical role in the control of cellular responses to stress and reward. In the current study, effects of acute and subchronic stress on the alteration of p-ERK, p-CREB and c-fos levels in the hypothalamus and hippocampus of saline- or morphine-treated animals during morphine-induced conditioned place preference (CPP) procedure were investigated. Male Wistar rats were divided into two saline- and morphine-treated supergroups. Each supergroup includes of control, acute stress and subchronic stress groups. In all of groups, the CPP procedure was done, afterward the alternation of p-ERK/ERK ratio, p-CREB/CREB ratio and c-fos level in the hypothalamus and hippocampus were estimated by Western blot analysis. The results indicated that in saline- or morphine-treated animals, p-ERK/ERK ratio, p-CREB/CREB ratio and c-fos level increased after application of acute and subchronic stress (except for p-ERK/ERK ratio in morphine-control group). Our findings revealed that in saline- or morphine-treated animals, acute and subcronic stress increased the p-ERK/ERK ratio, p-CREB/CREB ratio and c-fos level in the hypothalamus and hippocampus and this enhancement in morphine-treated animals, was more considerable than that in saline-treated animals.

  7. Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling.

    Directory of Open Access Journals (Sweden)

    Deborah C Mash

    2007-11-01

    Full Text Available The chronic effects of cocaine abuse on brain structure and function are blamed for the inability of most addicts to remain abstinent. Part of the difficulty in preventing relapse is the persisting memory of the intense euphoria or cocaine "rush". Most abused drugs and alcohol induce neuroplastic changes in brain pathways subserving emotion and cognition. Such changes may account for the consolidation and structural reconfiguration of synaptic connections with exposure to cocaine. Adaptive hippocampal plasticity could be related to specific patterns of gene expression with chronic cocaine abuse. Here, we compare gene expression profiles in the human hippocampus from cocaine addicts and age-matched drug-free control subjects. Cocaine abusers had 151 gene transcripts upregulated, while 91 gene transcripts were downregulated. Topping the list of cocaine-regulated transcripts was RECK in the human hippocampus (FC = 2.0; p<0.05. RECK is a membrane-anchored MMP inhibitor that is implicated in the coordinated regulation of extracellular matrix integrity and angiogenesis. In keeping with elevated RECK expression, active MMP9 protein levels were decreased in the hippocampus from cocaine abusers. Pathway analysis identified other genes regulated by cocaine that code for proteins involved in the remodeling of the cytomatrix and synaptic connections and the inhibition of blood vessel proliferation (PCDH8, LAMB1, ITGB6, CTGF and EphB4. The observed microarray phenotype in the human hippocampus identified RECK and other region-specific genes that may promote long-lasting structural changes with repeated cocaine abuse. Extracellular matrix remodeling in the hippocampus may be a persisting effect of chronic abuse that contributes to the compulsive and relapsing nature of cocaine addiction.

  8. The effects of black garlic ethanol extract on the spatial memory and estimated total number of pyramidal cells of the hippocampus of monosodium glutamate-exposed adolescent male Wistar rats.

    Science.gov (United States)

    Hermawati, Ery; Sari, Dwi Cahyani Ratna; Partadiredja, Ginus

    2015-09-01

    Monosodium glutamate (MSG) is believed to exert deleterious effects on various organs, including the hippocampus, likely via the oxidative stress pathway. Garlic (Alium sativum L.), which is considered to possess potent antioxidant activity, has been used as traditional remedy for various ailments since ancient times. We have investigated the effects of black garlic, a fermented form of garlic, on spatial memory and estimated the total number of pyramidal cells of the hippocampus in adolescent male Wistar rats treated with MSG. Twenty-five rats were divided into five groups: C- group, which received normal saline; C+ group, which was exposed to 2 mg/g body weight (bw) of MSG; three treatment groups (T2.5, T5, T10), which were treated with black garlic extract (2.5, 5, 10 mg/200 g bw, respectively) and MSG. The spatial memory test was carried out using the Morris water maze (MWM) procedure, and the total number of pyramidal cells of the hippocampus was estimated using the physical disector design. The groups treated with black garlic extract were found to have a shorter path length than the C- and C+ groups in the escape acquisition phase of the MWM test. The estimated total number of pyramidal cells in the CA1 region of the hippocampus was higher in all treated groups than that of the C+ group. Based on these results, we conclude that combined administration of black garlic and MSG may alter the spatial memory functioning and total number of pyramidal neurons of the CA1 region of the hippocampus of rats.

  9. Neurobiological toxicity of radiation in hippocampus

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    Son, Yeong Hoon; Kim, Joong Sun [Research center, Dongnam institute of radiological and Medical Sciences (DIRAMS), Busan (Korea, Republic of); Kim, Sung Ho; Moon, Chang Jong [College of Veterinary Medicine, Chonnam National University, Gwangju (Korea, Republic of)

    2014-11-15

    Ionizing radiation affects multiple organs, which differ in their apparent response. Nevertheless, the adult brain is less vulnerable to radiation than other radiosensitive organs. Clinically, patients receive partial large-field or whole-brain irradiation for cancer treatment yearly, long-term survivors increases, and thus, radiation induced side effects, including cognitive impairment, will become a major health problem. Although the most commonly reported noxious effects of irradiation occur via damage to DNA and consequent disruption of protein synthesis, there are also specific effects on biochemical pathways that have indirect effects on DNA transcription. The hippocampus dependent memory dysfunction is consistent with the changes in neurogenesis after 1 and 3 dyas after irradiation. At 30 and 90 days following irradiation, mice displayed significant depression-like behaviors. Hippocampal dysfunction during the chronic phase following cranial irradiation may be associated with decreases in the neurogenesis and synaptic plasticity related signals, concomitant with microglial reduction in the hippocampus.

  10. Effects of mild hypothermia on the ROS and expression of caspase-3 mRNA and LC3 of hippocampus nerve cells in rats after cardiopulmonary resuscitation.

    Science.gov (United States)

    Lu, Jian; Shen, Yi; Qian, Hui-Yin; Liu, Li-Jun; Zhou, Bao-Chun; Xiao, Yan; Mao, Jin-Ning; An, Guo-Yin; Rui, Ming-Zhong; Wang, Tao; Zhu, Chang-Lai

    2014-01-01

    Cardiac arrest (CA) is a common and serious event in emergency medicine. Despite recent improvements in resuscitation techniques, the survival rate of patients with CA is unchanged. The present study was undertaken to observe the effect of mild hypothermia (MH) on the reactive oxygen species (ROS) and the effect of neurological function and related mechanisms. Sixty-five healthy male Sprague Dawley (SD) adult rats were randomly (random number) divided into 2 groups: blank control group (n=5) and CPR group (n=60). CA was induced by asphyxia. The surviving rats were randomly (random number) divided into two groups: normothermia CPR group (NT) and hypothermia CPR group (HT). Normothermia of 37 °C was maintained in the NT group after return of spontaneous circulation (ROSC), hypothermal intervention of 32 °C was carried out in the HT group for 4 hours immediately after ROSC. Both the NT and HT groups were then randomly divided into 2 subgroups 12 hours and 24 hours after ROSC (NT-12, NT-24, HT-12, HT-24 subgroups). During observation, the neurological deficit scores (NDSs) was recorded, then the bilateral hippocampi were obtained from rats' head, and monoplast suspension of fresh hippocampus tissue was made immediately to determine the level of intracellular ROS by flow cytometry. Transmission electron microscope was used to observe the ultramicro changes of cellular nucleus and mitochondria. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression of caspase-3 mRNA, and western-blotting (WB) was used to determine the level of LC3 in frozen hippocampus tissue. Measured data were analyzed with paired sample t test and One-Way ANOVA. Of 60 rats with CA, 44 (73%) were successfully resuscitated and 33 (55%) survived until the end of the experiment. The NDSs of rats in the NT and HT groups were more significantly reduced than those in the BC group (F=8.107, Pnerve cells in the NT and HT groups significantly increased compared to the BC

  11. Endogenous synthesis of corticosteroids in the hippocampus.

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    Shimpei Higo

    Full Text Available BACKGROUND: Brain synthesis of steroids including sex-steroids is attracting much attention. The endogenous synthesis of corticosteroids in the hippocampus, however, has been doubted because of the inability to detect deoxycorticosterone (DOC synthase, cytochrome P450(c21. METHODOLOGY/PRINCIPAL FINDINGS: The expression of P450(c21 was demonstrated using mRNA analysis and immmunogold electron microscopic analysis in the adult male rat hippocampus. DOC production from progesterone (PROG was demonstrated by metabolism analysis of (3H-steroids. All the enzymes required for corticosteroid synthesis including P450(c21, P450(2D4, P450(11β1 and 3β-hydroxysteroid dehydrogenase (3β-HSD were localized in the hippocampal principal neurons as shown via in situ hybridization and immunoelectron microscopic analysis. Accurate corticosteroid concentrations in rat hippocampus were determined by liquid chromatography-tandem mass spectrometry. In adrenalectomized rats, net hippocampus-synthesized corticosterone (CORT and DOC were determined to 6.9 and 5.8 nM, respectively. Enhanced spinogenesis was observed in the hippocampus following application of low nanomolar (10 nM doses of CORT for 1 h. CONCLUSIONS/SIGNIFICANCE: These results imply the complete pathway of corticosteroid synthesis of 'pregnenolone →PROG→DOC→CORT' in the hippocampal neurons. Both P450(c21 and P450(2D4 can catalyze conversion of PROG to DOC. The low nanomolar level of CORT synthesized in hippocampal neurons may play a role in modulation of synaptic plasticity, in contrast to the stress effects by micromolar CORT from adrenal glands.

  12. Hippocampal Sclerosis: Causes and Prevention.

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    Walker, Matthew Charles

    2015-06-01

    Hippocampal sclerosis is the commonest cause of drug-resistant epilepsy in adults, and is associated with alterations to structures and networks beyond the hippocampus.In addition to being a cause of epilepsy, the hippocampus is vulnerable to damage from seizure activity. In particular, prolonged seizures (status epilepticus) can result in hippocampal sclerosis. The hippocampus is also vulnerable to other insults including traumatic brain injury, and inflammation. Hippocampal sclerosis can occur in association with other brain lesions; the prevailing view is that it is probably a secondary consequence. In such instances, successful surgical treatment usually involves the resection of both the lesion and the involved hippocampus. Experimental data have pointed to numerous neuroprotective strategies to prevent hippocampal sclerosis. Initial neuroprotective strategies aimed at glutamate receptors may be effective, but later, metabolic pathways, apoptosis, reactive oxygen species, and inflammation are involved, perhaps necessitating the use of interventions aimed at multiple targets. Some of the therapies that we use to treat status epilepticus may neuroprotect. However, prevention of neuronal death does not necessarily prevent the later development of epilepsy or cognitive deficits. Perhaps, the most important intervention is the early, aggressive treatment of seizure activity, and the prevention of prolonged seizures. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  13. Therapeutic testosterone administration preserves excitatory synaptic transmission in the hippocampus during autoimmune demyelinating disease.

    Science.gov (United States)

    Ziehn, Marina O; Avedisian, Andrea A; Dervin, Shannon M; Umeda, Elizabeth A; O'Dell, Thomas J; Voskuhl, Rhonda R

    2012-09-05

    Over 50% of multiple sclerosis (MS) patients experience cognitive deficits, and hippocampal-dependent memory impairment has been reported in >30% of these patients. While postmortem pathology studies and in vivo magnetic resonance imaging demonstrate that the hippocampus is targeted in MS, the neuropathology underlying hippocampal dysfunction remains unknown. Furthermore, there are no treatments available to date to effectively prevent neurodegeneration and associated cognitive dysfunction in MS. We have recently demonstrated that the hippocampus is also targeted in experimental autoimmune encephalomyelitis (EAE), the most widely used animal model of MS. The objective of this study was to assess whether a candidate treatment (testosterone) could prevent hippocampal synaptic dysfunction and underlying pathology when administered in either a preventative or a therapeutic (postdisease induction) manner. Electrophysiological studies revealed impairments in basal excitatory synaptic transmission that involved both AMPA receptor-mediated changes in synaptic currents, and faster decay rates of NMDA receptor-mediated currents in mice with EAE. Neuropathology revealed atrophy of the pyramidal and dendritic layers of hippocampal CA1, decreased presynaptic (Synapsin-1) and postsynaptic (postsynaptic density 95; PSD-95) staining, diffuse demyelination, and microglial activation. Testosterone treatment administered either before or after disease induction restores excitatory synaptic transmission as well as presynaptic and postsynaptic protein levels within the hippocampus. Furthermore, cross-modality correlations demonstrate that fluctuations in EPSPs are significantly correlated to changes in postsynaptic protein levels and suggest that PSD-95 is a neuropathological substrate to impaired synaptic transmission in the hippocampus during EAE. This is the first report demonstrating that testosterone is a viable therapeutic treatment option that can restore both hippocampal

  14. Detrimental effect of clomipramine on hippocampus-dependent learning in an animal model of obsessive-compulsive disorder induced by sensitization with d2/d3 agonist quinpirole.

    Science.gov (United States)

    Hatalova, Hana; Radostova, Dominika; Pistikova, Adela; Vales, Karel; Stuchlik, Ales

    2017-01-15

    Quinpirole (QNP) sensitization is one of the commonly used animal models of obsessive-compulsive disorder (OCD). We have previously shown that QNP-sensitized animals display a robust cognitive flexibility deficit in an active place avoidance task with reversal in Carousel maze. This is in line with numerous human studies showing deficits in cognitive flexibility in OCD patients. Here we explored the effect of clomipramine, an effective OCD drug that attenuates compulsive checking in QNP, on sensitized rats in acquisition and reversal performances in an active place avoidance task. We found that the addition of clomipramine to QNP-sensitization impairs acquisition learning to a degree that reversal learning could not be tested. In a hippocampal-independent two-way active avoidance task clomipramine did not have an effect on acquisition learning in QNP-treated rats; suggesting that the detrimental effect of clomipramine is hippocampus based. We also tested the effect of risperidone in QNP-sensitized animals, which is not effective in OCD treatment. Risperidone also marginally impaired acquisition learning of QNP-sensitized animals, but not reversal. Moreover, we explored the effect of the augmentation of clomipramine treatment with risperidone in QNP-sensitized rats- a common step in treating SRI-unresponsive OCD patients. Only under this treatment regime animals were unimpaired in both acquisition and reversal learning. Augmentation of SRI with neuroleptics therefore could be beneficial for improving cognitive flexibility, and possibly be considered a first line of treatment in patients with reduced cognitive flexibility. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Role of the hippocampus in memory functioning: modern view

    Directory of Open Access Journals (Sweden)

    D. O. Assonov

    2017-12-01

    Full Text Available The purpose of this review was to develop the comprehensive conception of the hippocampus role in the functioning of human memory, based on data obtained by analysis of the latest scientific literature on the topic and make recommendations for further ways of researches in this topic. The scientific literature of the last 5 years on the role of the hippocampus in memory functioning was analyzed. Based on the reviewed literature, we made the next conclusions: the hippocampus is an extremely important for memory structure with various connections for different types of memory; the hippocampus is affected by a variety of substances, most studied now are glucocorticosteroids, whose effect on memory differs depending on the start time of action; the hippocampus volume in mental disorders affecting memory is less than normal, which makes it an important diagnostic criterion; at the moment, various promising methods that can help in the therapy of PTSD, depression, phobias and other disorders associated with memory impairment and based on the knowledge of the hippocampus for the treatment of memory disorders are being developed. Based on these conclusions and data, which were analyzed, we offered the following recommendations: to implement the hippocampal function examination in the diagnostics of mental disorders, which are accompanied by a violation of its work; to use the size of the hippocampus as one of the prognostic factors for the severity of the memory-associated disorders and the therapy progress; to carefully investigate the difference in the effect of various psychotherapies and pharmacotherapies on the hippocampus to determine exactly which of the therapies is the most morphologically reasonable; to find out how significant the decrease in the hippocampal volume is for the memory functioning; to use pathogenetically and morphologically based methods to improve the function of the hippocampus in the treatment of disorders that are

  16. The hippocampus and visual perception

    Directory of Open Access Journals (Sweden)

    Andy C. H. Lee

    2012-04-01

    Full Text Available In this review, we will discuss the idea that the hippocampus may be involved in both memory and perception, contrary to theories that posit functional and neuroanatomical segregation of these processes. This suggestion is based on a number of recent neuropsychological and functional neuroimaging studies that have demonstrated that the hippocampus is involved in the visual discrimination of complex spatial scene stimuli. We argue that these findings cannot be explained by long-term memory or working memory processing or, in the case of patient findings, dysfunction beyond the medial temporal lobe. Instead, these studies point towards a role for the hippocampus in higher-order spatial perception. We suggest that the hippocampus processes complex conjunctions of spatial features, and that it may be more appropriate to consider the representations for which this structure is critical, rather than the cognitive processes that it mediates.

  17. Effects of chronic ethanol on cholinergic actions in rat hippocampus: electrophysiological studies and quantification of m1-m5 muscarinic receptor subtypes.

    Science.gov (United States)

    Rothberg, B S; Yasuda, R P; Satkus, S A; Wolfe, B B; Hunter, B E

    1993-12-24

    The effects of chronic ethanol treatment (CET) on cholinergic modulation of CA1 evoked field potentials and recurrent inhibition were investigated in rat hippocampal slices. Densities of muscarinic receptor subtypes were quantified in remaining hippocampal tissue by immunoprecipitation. Iontophoretic application of ACh in stratum pyramidale results in facilitation of single evoked population spikes; application in stratum radiatum results in depression of field EPSPs. CET decreased cholinergic facilitation of population spikes, while cholinergic inhibition of field EPSPs remained unaffected. Integrity of feedback (recurrent) inhibitory circuitry was evaluated by paired-pulse stimulation. As previously demonstrated, recurrent inhibition was significantly reduced after CET; cholinergic disinhibition was also significantly reduced. Thus, CET appears to disrupt a subset of cholinergic effector systems within hippocampal neurons. The reductions in cholinergic function produced by CET does not appear to be due to receptor loss, since muscarinic receptor subtype densities were not found to be significantly altered in this tissue. These results support the hypothesis that muscarinic receptor function is impaired in CA1 pyramidal cells through a disruption of intracellular signal transduction mechanisms. While it is unclear whether cholinergic function is reduced in interneurons directly, these results suggest that modulation of neuronal firing in the hippocampus is markedly altered following CET due to impairment of both cholinergic and GABAergic systems.

  18. Toluene Effects on Gene Expression in the Hippocampus of Young-Adult, Middle-Age and Senescent Brown Norway Rats

    Science.gov (United States)

    Differential susceptibility to environmental exposure(s) across life stages is an area of toxicology about which little is known. We examined the effects of toluene, a known neurotoxicant with reported behavioral, electrophysiological and pathological effects, on transcriptomic...

  19. Evaluating the Effectiveness of Forensic Psychiatric Prevention

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    Makushkina O.A.,

    2014-11-01

    Full Text Available We discuss the quantitative indicators, the analysis of which gives an idea of the strengths and means at the disposal of forensic health care. We discuss the possibility of using the existing statistical monitoring system for a dynamic assessment of the quality of the measures for primary prevention of socially dangerous acts and implementation of compulsory medical measures at the regional and federal levels. We emphasize the quality indicators of the process for specialized assistance: security environment, organizational culture, training and upgrading the skills of staff, completeness and quality of psychosocial interventions, the degree of profiling the psycho-educational work, the quality of psychotherapeutic contact and its dynamics. We discuss the problem of the validity of the criteria of rehabilitation interventions success by compliance with the methodological principles for the evaluation of their effectiveness. We suggest ways to improve the effectiveness of regional mental health services for the prevention of socially dangerous acts, approaches to peer review and monitoring of the work

  20. Ovariectomy-Induced Mitochondrial Oxidative Stress, Apoptosis, and Calcium Ion Influx Through TRPA1, TRPM2, and TRPV1 Are Prevented by 17β-Estradiol, Tamoxifen, and Raloxifene in the Hippocampus and Dorsal Root Ganglion of Rats.

    Science.gov (United States)

    Yazğan, Yener; Nazıroğlu, Mustafa

    2017-12-01

    Relative 17β-estradiol (E2) deprivation and excessive production of mitochondrial oxygen free radicals (OFRs) with a high amount of Ca2+ influx TRPA1, TRPM2, and TRPV1 activity is one of the main causes of neurodegenerative disease in postmenopausal women. In addition to the roles of tamoxifen (TMX) and raloxifene (RLX) in cancer and bone loss treatments, regulator roles in Ca2+ influx and mitochondrial oxidative stress in neurons have not been reported. The aim of this study was to evaluate whether TMX and RLX interactions with TRPA1, TRPM2, and TRPV1 in primary hippocampal (HPC) and dorsal root ganglion (DRG) neuron cultures of ovariectomized (OVX) rats. Forty female rats were divided into five groups: a control group, an OVX group, an OVX+E2 group, an OVX+TMX group, and an OVX+RLX group. The OVX+E2, OVX+TMX, and OVX+RLX groups received E2, TMX, and RLX, respectively, for 14 days after the ovariectomy. E2, ovariectomy-induced TRPA1, TRPM2, and TRPV1 current densities, as well as accumulation of cytosolic free Ca2+ in the neurons, were returned to the control levels by E2, TMX, and RLX treatments. In addition, E2, TMX, and RLX via modulation of TRPM2 and TRPV1 activity reduced ovariectomy-induced mitochondrial membrane depolarization, apoptosis, and cytosolic OFR production. TRPM2, TRPV1, PARP, and caspase-3 and caspase-9 expressions were also decreased in the neurons by the E2, TMX, and RLX treatments. In conclusion, we first reported the molecular effects of E2, TMX, and RLX on TRPA1, TRPM2, and TRPV1 channel activation in the OVX rats. In addition, we observed neuroprotective effects of E2, RLX, and TMX on oxidative and apoptotic injuries of the hippocampus and peripheral pain sensory neurons (DRGs) in the OVX rats. Graphical Abstract Possible molecular pathways of involvement of DEX in cerebral ischemia-induced apoptosis, oxidative stress, and calcium accumulation through TRPA1, TRPM2 and TRPV1 in the hippocampus and DRG neurons of rats. The N domain of the

  1. Anxiolytic-like effects after vector-mediated overexpression of neuropeptide Y in the amygdala and hippocampus of mice

    DEFF Research Database (Denmark)

    Christiansen, Søren Hofman Oliveira; Olesen, Mikkel Vestergaard; Gøtzsche, Casper René

    2014-01-01

    Neuropeptide Y (NPY) causes anxiolytic- and antidepressant-like effects after central administration in rodents. These effects could theoretically be utilized in future gene therapy for anxiety and depression using viral vectors for induction of overexpression of NPY in specific brain regions...

  2. Differential effects of quercetin on hippocampus-dependent learning and memory in mice fed with different diets related with oxidative stress.

    Science.gov (United States)

    Xia, Shu-Fang; Xie, Zhen-Xing; Qiao, Yi; Li, Li-Rong; Cheng, Xiang-Rong; Tang, Xue; Shi, Yong-Hui; Le, Guo-Wei

    2015-01-01

    High fat diets induce oxidative stress which may be involved in neurodegenerative diseases. Quercetin is a kind of antioxidant that has neuroprotective effects and potent7ial pro-oxidant effects as well. In this study, we evaluated cognitive function in mice fed with high fat diets and basic diets with or without quercetin. Male Chinese Kunming (KM) mice were randomly assigned to five groups fed with basic diet (Control), basic diet with 0.005% (w/w) quercetin (CQ1), high fat diet (HFD), HFD with 0.005% (w/w) quercetin (HFDQ1) and 0.01% (w/w) quercetin (HFDQ2) for 13weeks. At the end of the study period, fasting blood glucose (FBG), plasma and hippocampal markers of oxidative stress, plasma lipid status, Morris water maze as well as hippocampal relative mRNA expression of akt, bdnf, camkII, creb, gsk-3β, nrf2 and pi3k were examined. The results suggested that in comparison to the control group, the escape latency was increased and percent time spent in the target quadrant was decreased, with increased reactive carbonyls, malondialdehyde (MDA) and declined expression of pi3k, akt, nrf2, creb and bdnf in the hippocampus of HFD and CQ1 groups. Conversely, higher quercetin supplemented to HFD improved antioxidant capacity and reversed cognitive decline completely. Significant correlations between the redox status and cognition-related gene expression were observed as well (Phippocampus dependent cognition. But under a balanced situation, quercetin exerts pro-oxidant effects to impair cognition. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Effects of isolation rearing and early antipsychotic intervention on oxidative stress-induced apoptosis and brain-derived neurotrophic factor in hippocampus in a rat model of schizophrenia

    Directory of Open Access Journals (Sweden)

    Szu-Nian Yang

    2017-01-01

    Full Text Available Background: Oxidative stress-induced neuronal dysfunction has been considered an essential factor for the development of schizophrenia. However, a longitudinal and causal relation between the impacts of developmental stress and oxidative stress remains unsolved. The present study aimed to examine whether the oxidative stress-relevant dysfunctions of the apoptotic index can be induced in rats of isolation rearing (IR, a rodent model of schizophrenia and to see if the intervention of antipsychotics can reverse these dysfunctions. Materials and Methods: Pharmacological manipulation (risperidone [RIS] [1 mg/kg/day], olanzapine [OLA] [2.5 mg/kg/day], or saline [SAL] vehicle was introduced 4 weeks (adolescence or 8 weeks (young adulthood after IR (i.e., rats were 7- or 11-week-old. The regime of RIS, OLA, or SAL was continued for 9 weeks. Locomotor activity was employed to validate the IR effect. Rats' hippocampus immediately after sacrifice was removed to measure messenger RNA expression of Bax, Bcl-2, brain-derived neurotrophic factor (BDNF and the plasma level of nitric oxide (NO. Results: The results showed: (i IR rats were more hyperactive. (ii RIS may exert anti-apoptotic effects on IR rats, particularly at their adolescent age (as indexed by increased Bcl-2 and decreased Bax/Bcl-2 ratio. (iii The therapeutic potential of RIS can be also observed in the change of BDNF in an age-independent manner, in which RIS effectively increased the BDNF level in IR but not social (SOC rats. (iv Plasma NO was not altered. Conclusion: The study results support the utility of the IR paradigm in exploring mental disorders with neurodevelopmental origin in which early pharmacological intervention may provide a therapeutic benefit in the overloaded oxidative stress and the dysfunction of BDNF.

  4. Developmental Exposure to A Commercial PBDE Mixture: Effects on Protein Networks in the Cerebellum and Hippocampus of Rats

    Science.gov (United States)

    BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are structurally similar topolychlorinated biphenyls (PCBs) and have both central (learning and memory deficits) and peripheral (motor dysfunction) neurotoxic effects at concentrations/doses similar to those of PCBs. The cellular...

  5. Does the hippocampus keep track of time?

    Science.gov (United States)

    Palombo, D J; Keane, M M; Verfaellie, M

    2016-03-01

    In the present study, we examined the role of the medial temporal lobe (MTL) in prospective time estimation at short and long timescales using a novel behavioral paradigm adapted from rodent work. Amnesic patients with MTL damage and healthy control participants estimated the duration of nature-based video clips that were either short (≤ 90 s) or long (more than 4 min). Consistent with previous work in rodents, we found that amnesic patients were impaired at making estimations for long, but not for short durations. Critically, these effects were observed in patients who had lesions circumscribed to the hippocampus, suggesting that the pattern observed was not attributable to the involvement of extra-hippocampal structures. That the MTL, and more specifically the hippocampus, is critical for prospective temporal estimation only at long intervals suggests that multiple neurobiological mechanisms support prospective time estimation. © 2015 Wiley Periodicals, Inc.

  6. The effect of intra-nucleus accumbens administration of allopregnanolone on δ and γ2 GABA(A) receptor subunit mRNA expression in the hippocampus and on depressive-like and grooming behaviors in rats.

    Science.gov (United States)

    Nin, Maurício S; Ferri, Marcelo K; Couto-Pereira, Natividade S; Souza, Marilise F; Azeredo, Lucas A; Agnes, Grasiela; Gomez, Rosane; Barros, Helena M T

    2012-12-01

    Alterations in GABA(A) receptor expression have been associated with the allopregnanolone (3α-hydroxy-5α-pregnan-20-one; 3α,5α-THP) antidepressant-like effect in rats. The present study aimed to verify the effect of bilateral, intra-nucleus accumbens core (intra-AcbC) administration of the neurosteroid allopregnanolone on behaviors in the forced swim and grooming microstructure tests and in the δ and γ2 GABA(A) receptor subunit mRNA expression in right and left hippocampus of rats. The results of this study showed that bilateral, intra-AcbC allopregnanolone administration (5μg/rat) presented antidepressant-like activity in the forced swim test concomitant with an increase in climbing. Allopregnanolone at doses of 1.25 and 5μg/rat also decreased the percentage of correct transitions in the grooming microstructure test. Both δ and γ2 GABA(A) subunit expressions increased in the rat hippocampus after allopregnanolone intra-AcbC treatment. Our findings point to asymmetrical GABA(A) receptor expression changes in the hippocampus of animals treated with allopregnanolone. Further investigation should evaluate the antidepressant-like effect of allopregnanolone not only in other directly infused regions but also with respect to changes in other brain areas of the limbic system to understand allopregnanolone's mechanism of action. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Study The Effect of 4 weeks of Special Aerobic Training on CBS and SAM Levels in Hippocampus of Rats with Alzheimer-induced Disease with Aβ1-42 Injection

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    Farhad Azimi

    2018-03-01

    Full Text Available Abstract Background: H2S plays a key role in the pathogenesis of the Alzheimer’s disease. The aim of the present study was to investigate the effects of 4 weeks of the special aerobic training after induction of Alzheimer’s disease by Aβ1-42 injection on CBS and SAM levels in hippocampus of Wistar male rats. Materials and Methods: Twenty male Wistar rats (8 weeks old and weight 195 ± 20 g were divided into four groups including: healthy control, Alzheimer’s control, Alzheimer’s + training and sham. To induce Alzheimer’s disease, Aβ1-42 was infused into the hippocampus of rats. Training group trained for 4-week. For data analysis, one-way ANOVA was used and Eta and Omega squared tests were used to determine the effect size (p<0.05. Results: Findings revealed that 4 weeks of special aerobic training increased significantly the CBS and SAM levels in hippocampus of Alzheimer’s rats compared to the control Alzheimer’s rats ( ES=53; p= 0.007, ES= 92.22; p= 0.001. Also, we showed 4 weeks of special aerobic training increased CBS level in hippocampus of Alzheimer’s rats compared to the healthy cotrol group (ES= 44.07; p= 0.014. Conclusion: It seems that the special aerobic training can be used as a useful non-pharmacologically effective therapeutic treatment for Alzheimer's patients through positive regulation of hydrogen sulfide via CBS and SAM enzymes.

  8. Naringin Attenuates Autophagic Stress and Neuroinflammation in Kainic Acid-Treated Hippocampus In Vivo

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    Kyoung Hoon Jeong

    2015-01-01

    Full Text Available Kainic acid (KA is well known as a chemical compound to study epileptic seizures and neuronal excitotoxicity. KA-induced excitotoxicity causes neuronal death by induction of autophagic stress and microglia-derived neuroinflammation, suggesting that the control of KA-induced effects may be important to inhibit epileptic seizures with neuroprotection. Naringin, a flavonoid in grapefruit and citrus fruits, has anti-inflammatory and antioxidative activities, resulting in neuroprotection in animal models from neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. In the present study, we examined its beneficial effects involved in antiautophagic stress and antineuroinflammation in the KA-treated hippocampus. Our results showed that naringin treatment delayed the onset of KA-induced seizures and decreased the occurrence of chronic spontaneous recurrent seizures (SRS in KA-treated mice. Moreover, naringin treatment protected hippocampal CA1 neurons in the KA-treated hippocampus, ameliorated KA-induced autophagic stress, confirmed by the expression of microtubule-associated protein light chain 3 (LC3, and attenuated an increase in tumor necrosis factor-α (TNFα in activated microglia. These results suggest that naringin may have beneficial effects of preventing epileptic events and neuronal death through antiautophagic stress and antineuroinflammation in the hippocampus in vivo.

  9. Effect of chronic aluminum exposure on the levels of conjugated dienes and enzymatic antioxidants in hippocampus and whole brain of rat

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, A.; Shukla, G.S. [Industrial Toxicology Research Centre, Lucknow (India)

    1995-11-01

    The reported association between elevated tissue levels of aluminum (Al) and certain human neurological disorders have evoked increasing attention on the neurotoxic effects of aluminum. High levels of Al have been reported in hippocampal neurons comprising neurofibrillary tangles in senile dementia of Alzheimer`s type, amyotropic lateral sclerosis and Parkinsonian dementia of Guam. Aluminum is considered to be the causal factor for a high incidence of dialysis encephalopathy. It has been shown that the incidence of Alzheimer`s disease was higher in places with a high Al content in drinking water compared to low level areas. Varied uses of Al in pharmaceutical preparations, foods, water purification and many house-hold items have increased the risk of its exposure to general population. The exposure may be as high as 500 mg/kg/day in children with uremia who are treated with Al containing phosphate binding gels. Aluminum ingestion in humans and experimental animals have been reported to produce behavioural dysfunctions. The mechanism of al neurotoxicity is not understood at present. Attempts made in this direction have reported its interaction with blood-brain barrier function, decreased membrane fluidity, glutathione depletion and increased brain lipid peroxidation. These studies indicate the possibility that oxidative stress may be one of the possible mechanisms of Al-induced neurotoxicity. Since Al has been reported to be in high concentrations in hippocampal neurons in certain neurological diseases and there is wealth of evidence implicating hippocampal impairment and memory dysfunction, we attempted to investigate the effect of chronic Al intoxication on the status of enzymatic antioxidants and the extent of peroxidative damage in hippocampus and whole brain of rat. 16 refs., 4 figs., 1 tab.

  10. The Effects of Combined Atorvastatin and Zinc Oxide on Some Markers of Oxidative Stress in the Hippocampus in Streptozotocin-induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Z Karampour Qipchaq

    2016-11-01

    Full Text Available Background & aim: Diabetes is a metabolic disorder characterized by hyperglycemia. Hyperglycemia through enzymatic and non-enzymatic processes causes induction of spontaneous oxidation of glucose and, by stimulating the production of active oxygen and nitrogen components, leading to oxidative stress. Thus, according to the antioxidant effects of atorvastatin and zinc oxide, the aim of this study  was to investigate the combined effect of atorvastatin and zinc oxide on oxidative stress and antioxidants in diabetic rats. Methods: In the present experimental study, 50 female Wistar rats were selected randomly and divided into five groups of 10 (n=10 including : normal control (NC, diabetic control (DC, diabetic rats treated with, atorvastatin (20mg/kg daily-orally (DA, zinc oxide (30mg/kg daily-rally (DZ and combination of each drug in half-dose (daily-orally (DAZ, were each treated separately. Diabetic rats were induced by injection of 60 mg per kg of body weight of streptozotocin (STZ intraperitoneally.All treatments were dissolved in distilled water for four weeks. After completion of treatment (forth week, weight and blood sugar were measured and then compared with data measured  on weight and blood sugar in the weeks before the start  and second week of the study. The lipid peroxidation level (MDA, the activity of catalase (CAT and total antioxidant capacity (TAC as an indicator of oxidative stress were measured in the hippocampus. Data were analyzed using ANOVA and Tukey tests. Results: Zinc oxide and atorvastatin alone rather than decrease blood sugar, reduced the complications of diabetes, including oxidative damage and combination  of both reduced levels of diabetic complications led to the significant decrease in blood glucose levels and inhibiting the animal lose weight. Conclusion: It seemed that the combination of atorvastatin and zinc oxide have synergistic benefits to control blood sugar levels and oxidative stress, and also

  11. Effects of Early Life Stress on Synaptic Plasticity in the Developing Hippocampus of Male and Female Rats

    NARCIS (Netherlands)

    Derks, Nienke A V; Krugers, Harm J; Hoogenraad, Casper C; Joëls, Marian; Sarabdjitsingh, R Angela

    2016-01-01

    INTRODUCTION: Early life stress (ELS) increases the risk for developing psychopathology in adulthood. When these effects occur is largely unknown. We here studied at which time during development ELS affects hippocampal synaptic plasticity, from early life to adulthood, in a rodent ELS model.

  12. A Funny Thing Happened on the Way to the Hippocampus: The Effects of Humor on Student Achievement and Memory Retention

    Science.gov (United States)

    McCartney Matthews, Melissa Lee

    2011-01-01

    Research literature relating to the use of humor as a teaching method or curricula specifically designed to include humor was reviewed to investigate the effects of humor on student learning in various environments from elementary schools to post-secondary classrooms. In this multi-method study, four instruments and a humor treatment were selected…

  13. Effects of experimental cerebral malaria in memory, brain-derived neurotrophic factor and acetylcholinesterase activity [correction for acitivity] in the hippocampus of survivor mice.

    Science.gov (United States)

    Comim, Clarissa M; Reis, Patrícia A; Frutuoso, Valber S; Fries, Gabriel R; Fraga, Daiane B; Kapczinski, Flávio; Zugno, Alexandra I; Barichello, Tatiana; Quevedo, João; Castro-Faria-Neto, Hugo C

    2012-08-15

    Malaria is the most important human parasitic disease and cerebral malaria (CM), its main neurological complication, is characterized by neurological and cognitive damage in both human and animal survivors. The brain-derived neurotrophic factor (BDNF) appears to be involved with activity-dependent synaptic plasticity. There is great interest regarding its role in learning and memory as well as acetylcholinesterase activity (AChE) that is implicated in many cognitive functions and probably plays important roles in neurodegenerative disorders. In the present work, we evaluated BDNF protein levels and AChE activity in the hippocampus and habituation in an animal model of CM using C57BL/6 mice after fifteen days of the induction. The results demonstrated that there was a decrease in BDNF levels in the hippocampus of C57BL/6 mice infected with PbA when compared with C57BL/6 non-infected mice and C57BL/6 non-infected mice that received treatment with chloroquine. However, no difference was observed in AChE activity in the hippocampus. When habituation was evaluated there was memory impairment in the C57BL/6 mice infected with Plasmodium berghei ANKA (PbA). In conclusion, we believe that the decreased BDNF levels in the hippocampus may be related with memory impairment without alterations on AChE activity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK

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    Li, Ying; Li, Jia; Li, Shanshan; Li, Yi; Wang, Xiangxiang; Liu, Baolin [Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 639, Longmian Road, Nanjing 211198 (China); Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, 639, Longmian Road, Nanjing 211198 (China); Fu, Qiang, E-mail: fuqiang@cpu.edu.cn [Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 639, Longmian Road, Nanjing 211198 (China); Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, 639, Longmian Road, Nanjing 211198 (China); Ma, Shiping, E-mail: spma@cpu.edu.cn [Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 639, Longmian Road, Nanjing 211198 (China); Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, 639, Longmian Road, Nanjing 211198 (China)

    2015-07-01

    Curcumin is a natural polyphenolic compound in Curcuma longa with beneficial effects on neuronal protection. This study aims to investigate the action of curcumin in the hippocampus subjected to glutamate neurotoxicity. Glutamate stimulation induced reactive oxygen species (ROS), endoplasmic reticulum stress (ER stress) and TXNIP/NLRP3 inflammasome activation, leading to damage in the hippocampus. Curcumin treatment in the hippocampus or SH-SY5Y cells inhibited IRE1α and PERK phosphorylation with suppression of intracellular ROS production. Curcumin increased AMPK activity and knockdown of AMPKα with specific siRNA abrogated its inhibitory effects on IRE1α and PERK phosphorylation, indicating that AMPK activity was essential for the suppression of ER stress. As a result, curcumin reduced TXNIP expression and inhibited NLRP3 inflammasome activation by downregulation of NLRP3 and cleaved caspase-1 induction, and thus reduced IL-1β secretion. Specific fluorescent probe and flow cytometry analysis showed that curcumin prevented mitochondrial malfunction and protected cell survival from glutamate neurotoxicity. Moreover, oral administration of curcumin reduced brain infarct volume and attenuated neuronal damage in rats subjected to middle cerebral artery occlusion. Immunohistochemistry showed that curcumin inhibited p-IRE1α, p-PERK and NLRP3 expression in hippocampus CA1 region. Together, these results showed that curcumin attenuated glutamate neurotoxicity by inhibiting ER stress-associated TXNIP/NLRP3 inflammasome activation via the regulation of AMPK, and thereby protected the hippocampus from ischemic insult. - Highlights: • Curcumin attenuates glutamate neurotoxicity in the hippocampus. • Curcumin suppresses ER stress in glutamate-induced hippocampus slices. • Curcumin inhibits TXNIP/NLRP3 inflammasome activation. • Regulation of AMPK by curcumin contributes to suppressing ER stress.

  15. [Effect of multiple-micronutrient supplementation on learning and memorizing ability of young rats and the ultra-structure in CA3 region of hippocampus of rat's brain].

    Science.gov (United States)

    Liang, Aihua; Chen, Yikun; Zhang, Wen; Hong, Junrong

    2009-01-01

    To study the effects of multiple-micronutrient on the learning and memory ability of young rats using shuttle-box, as well as to observe the ultra-structure and the synaptophysin (SYN) immunoreactive expression in the region of hippocampal CA3. Forty 5-week-old male Sprague-Dawley rats were randomized divided into control group and 3 test groups by body weight. Rats were injected intraperitoneally with multiple-micronutrient [0 g/(kg x d), 0.74 g/(kg x d), 1.48 g/(kg x d) and 2.22 g/(kg x d)] once per day for 30 days. Active avoidance behayior of learning and memory performance in different groups were measured by shuttle-box. The immune expression of Syn in the region of hippoeampal CA3 were tested with immunohistochemical method. Moreover, ultrastructural pathologic features of the CA3 region of hippocampus were investigated by transmission electron microscope. The shuttle-box test showed that the time of escape reaction of high-dose group (13.15 +/- 8.106, 9.50 +/- 5.063) was longer (P < 0.05) than that of control group. The results revealed a significant increase in the number of synapses, the thickness of postsynaptic density, synaptic curvature and the absorbency of positive product of Syn immunoreaction in the region of hippocampal CA3 in high-dose group compared with control group, which were significant difference (P < 0.05). Our study suggests that synaptic plasticity might be the probable mechanism on improving the learning and memory ability by multiple-micronutrient in young rats.

  16. Effects of Different Training Loads on Emotional State and mRNA and Protein Expressions of N-Methyl-D-Aspartate Receptor Subunits, Postsynaptic Density 95, and Kinesin Family Member 17 in Hippocampus of Rats

    Science.gov (United States)

    Ren, Hefei; Yu, Xinyi; Yu, Liren; Zhang, Yinguo; Xie, Hong; Shi, Na; Chen, Lijun

    2017-01-01

    Background Emotional state can be affected by different training loads. The aim of this study was to explore the changes of rat emotional state, as well as the mRNA and protein expressions of N-methyl-D-aspartate receptors (NMDARs), postsynaptic density 95 (PSD-95), and kinesin family member 17 (KIF-17) in the hippocampus, by long-term moderate-intensity and high-intensity training models in rats. Material/Methods The exercise model of SD rats was set up by treadmill running of moderate and high intensities for 4 weeks. The rats in the moderate-intensity training group were given endurance training with increasing intensity, while rats in the high-intensity training group were given high-speed training, and those in the normal control group were also established. The body weights of rats were measured before and after exercise to determine weight reduction. Real-time PCR and Western blotting were used to detect the mRNA and protein expressions of NMDARs, PSD-95, and KIF-17 in hippocampus of rats under different training loads. Results Compared with the control group, the rats in the moderate-intensity training group had better body condition and emotional state, while the rats in the high-intensity training group had poor body condition and emotional state. The mRNA and protein expression of PSD-95, KIF-17, and NMDARs in the moderate-intensity training group were significantly elevated (Ptraining group were suppressed (Ptraining loads have remarkable influences on the cognition, emotion, and mental status of rats, and can affect the mRNA and protein expressions of NMDARs, PSD-95, and KIF-17 in rats. Appropriate training loads alleviate hypoxia damage to the hippocampus, and also effectively improve hippocampus function. PMID:29038420

  17. Effects of L-arginine and N(ω)-nitro-L-arginine methylester on learning and memory and α7 nAChR expression in the prefrontal cortex and hippocampus of rats.

    Science.gov (United States)

    Wei, Xiao-Ming; Yang, Wei; Liu, Li-Xia; Qi, Wen-Xiu

    2013-06-01

    Nitric oxide (NO) is a novel type of neurotransmitter that is closely associated with synaptic plasticity, learning and memory. In the present study, we assessed the effects of L-arginine and N(ω)-nitro-L-arginine methylester (L-NAME, a nitric oxide synthase inhibitor) on learning and memory. Rats were assigned to three groups receiving intracerebroventricular injections of L-Arg (the NO precursor), L-NAME, or 0.9% NaCl (control), once daily for seven consecutive days. Twelve hours after the last injection, they underwent an electric shock-paired Y maze test. Twenty-four hours later, the rats' memory of the safe illuminated arm was tested. After that, the levels of NO and α7 nicotinic acetylcholine receptor (α7 nAChR) in the prefrontal cortex and hippocampus were assessed using an NO assay kit, and immunohistochemistry and Western blots, respectively. We found that, compared to controls, L-Arg-treated rats received fewer foot shocks and made fewer errors to reach the learning criterion, and made fewer errors during the memory-testing session. In contrast, L-NAME-treated rats received more foot shocks and made more errors than controls to reach the learning criterion, and made more errors during the memory-testing session. In parallel, NO content in the prefrontal cortex and hippocampus was higher in L-Arg-treated rats and lower in L-NAME rats, compared to controls. Similarly, α7 nAChR immunoreactivity and protein expression in the prefrontal cortex and hippocampus were higher in L-Arg-treated rats and lower in L-NAME rats, compared to controls. These results suggest that the modulation of NO content in the brain correlates with α7 nAChR distribution and expression in the prefrontal cortex and hippocampus, as well as with learning and memory performance in the Y-maze.

  18. Musical training induces functional plasticity in human hippocampus.

    Science.gov (United States)

    Herdener, Marcus; Esposito, Fabrizio; di Salle, Francesco; Boller, Christian; Hilti, Caroline C; Habermeyer, Benedikt; Scheffler, Klaus; Wetzel, Stephan; Seifritz, Erich; Cattapan-Ludewig, Katja

    2010-01-27

    Training can change the functional and structural organization of the brain, and animal models demonstrate that the hippocampus formation is particularly susceptible to training-related neuroplasticity. In humans, however, direct evidence for functional plasticity of the adult hippocampus induced by training is still missing. Here, we used musicians' brains as a model to test for plastic capabilities of the adult human hippocampus. By using functional magnetic resonance imaging optimized for the investigation of auditory processing, we examined brain responses induced by temporal novelty in otherwise isochronous sound patterns in musicians and musical laypersons, since the hippocampus has been suggested previously to be crucially involved in various forms of novelty detection. In the first cross-sectional experiment, we identified enhanced neural responses to temporal novelty in the anterior left hippocampus of professional musicians, pointing to expertise-related differences in hippocampal processing. In the second experiment, we evaluated neural responses to acoustic temporal novelty in a longitudinal approach to disentangle training-related changes from predispositional factors. For this purpose, we examined an independent sample of music academy students before and after two semesters of intensive aural skills training. After this training period, hippocampal responses to temporal novelty in sounds were enhanced in musical students, and statistical interaction analysis of brain activity changes over time suggests training rather than predisposition effects. Thus, our results provide direct evidence for functional changes of the adult hippocampus in humans related to musical training.

  19. [Which diet for an effective cardiovascular prevention?].

    Science.gov (United States)

    Sofi, Francesco; Abbate, Rosanna; Gensini, Gian Franco; Casini, Alessandro

    2012-06-01

    Over the last years, numerous evidence on the existing relationship between nutrition and chronic degenerative diseases have led investigators to search for the optimal dietary pattern to maintain a good health status. It's well known, in fact, that nutrition is capable of substantially modifying the risk profile ofa subject in primary and/or secondary prevention. Several models of diet have been imposed on public attention, but the one that got the most interest is certainly the Mediterranean diet. Recently, several studies have shown that a strict adherence to a Mediterranean dietary pattern is associated with a lower incidence of mortality and incidence of chronic degenerative diseases such as cardiovascular disease and cancer. Meta-analyses conducted by our group have revealed, in a population of over than 2 million of people, that adherence to Mediterranean diet determines a significant reduction on the risk of cardiovascular and cerebrovascular accidents. To the best of the knowledge the most effective indications for an optimal therapeutic strategy in nutrition include: increase the consumption of fruits and vegetables up to the recommended 5 servings a day, prefer whole grains, replace saturated and trans fats with unsaturated fats, reduce the consumption of sugar and sweetened beverages, and limit salt intake. With these simple indications, together with recommendations of following the principles of the traditional Mediterranean diet, a substantial reduction of the risk of incidence and/or mortality from cardiovascular disease can be easily obtained.

  20. Basolateral amygdala activity is required for enhancement of memory consolidation produced by histone deacetylase inhibition in the hippocampus.

    Science.gov (United States)

    Blank, Martina; Dornelles, Arethuza S; Werenicz, Aline; Velho, Luciana A; Pinto, Diana F; Fedi, Ana Cláudia; Schröder, Nadja; Roesler, Rafael

    2014-05-01

    Histone acetylation, a type of chromatin modification that allows increased gene transcription and can be pharmacologically promoted by histone deacetylase (HDAC) inhibitors (HDACis), has been consistently associated with promoting memory formation in the hippocampus. The basolateral nucleus of the amygdala (BLA) is a brain area crucially involved in enabling hormones and drugs to influence memory formation. Here, we show that BLA activity is required for memory enhancement by intrahippocampal administration of an HDACi. Two different HDACis, sodium butyrate (NaB) and trichostatin A (TSA), differentially enhanced the retention of memory for inhibitory avoidance (IA) when administered to the dorsal hippocampus after training. TSA showed a biphasic pattern of response during consolidation, in which infusions given immediately or 3h after training produced memory enhancement, whereas no effect was observed when it was infused 1.5 or 6h posttraining. Muscimol (MUS)-induced unilateral functional inactivation of the BLA prevented the enhancement of memory retention produced by posttraining infusion of TSA into the ipsilateral hippocampus. TSA did not affect IA extinction or reconsolidation. These results indicate that HDACis can increase IA memory retention when given into the hippocampus, and, most importantly, BLA activity is necessary for enabling HDACi-induced influences on memory formation. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. The Pattern of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampus of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Iraj Salehi

    2010-06-01

    Full Text Available Objective(sThe aim of this study was to evaluate the effects of regular exercise in preventing diabetes complication in the hippocampus of streptozotocin (STZ-induced diabetic rat.Materials and MethodsA total of 48 male wistar rats were divided into four groups (control, control exercise, diabetic and diabetic exercise. Diabetes was induced by injection of single dose of STZ. Exercise was performed for one hr every day, over a period of 8 weeks. The antioxidant enzymes (SOD, GPX, CAT and GR and oxidant indexes with brain-derived neurotrophic factor (BDNF protein and its mRNA and apoptosis were measured in hippocampus of rats. ResultsA significant decrease in antioxidant enzymes activities and increased malondialdehyde (MDA level were observed in diabetic rats (P= 0.004. In response to exercise, antioxidant enzymes activities increased (P= 0.004. In contrast, MDA level decreased in diabetic rats (P= 0.004. Induction of diabetes caused an increase of BDNF protein and its mRNA expression. In response to exercise, BDNF protein and its mRNA expression reduced in hippocampus of diabetic rats. ConclusionDiabetes induced oxidative stress and increased BDNF gene expression. Exercise ameliorated oxidative stress and decreased BDNF gene expression.

  2. The bumps on the hippocampus

    Science.gov (United States)

    Gao, Yi; Ver Hoef, Lawrence

    2016-03-01

    The hippocampus has been the focus of more imaging research than any other subcortical structure in the human brain. However a feature that has been almost universally overlooked are the bumpy ridges on the inferior aspect of the hippocampus, which we refer to as hippocampal dentation. These bumps arise from folds in the CA1 layer of Ammon's horn. Similar to the folding of the cerebral cortex, hippocampal dentation allows for greater surface area in a confined space. However, while quantitative studies of radiologic brain images have been advancing for decades, examining numerous approaches to hippocampal segmentation and morphology analysis, virtually all published 3D renderings of the hippocampus show the under surface to be quite smooth or mildly irregular; we have rarely seen the characteristic bumpy structure in the reconstructed 3D scene, one exception being the 9.4T postmortem study. This is presumably due to the fact that, based on our experience with high resolution images, there is a dramatic degree of variability in hippocampal dentation between individuals from very smooth to highly dentated. An apparent question is, does this indicate that this specific morphological signature can only be captured using expensive ultra-high field techniques? Or, is such information buried in the data we commonly acquire, awaiting a computation technique that can extract and render it clearly? In this study, we propose a super-resolution technique that captures the fine scale morphometric features of the hippocampus based on common T1-weighted 3T MR images.

  3. Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

    Science.gov (United States)

    Kutlu, Munir Gunes

    2016-01-01

    It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawal-induced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates. PMID:27634143

  4. Coenzyme Q10: Can It Prevent Statin Side Effects?

    Science.gov (United States)

    ... Q10: Can it prevent statin side effects? Can coenzyme Q10 reduce the risk of side effects from statins? ... Francisco Lopez-Jimenez, M.D. At this time, coenzyme Q10 isn't universally recommended for preventing side effects ...

  5. Neural Representations of Location Outside the Hippocampus

    Science.gov (United States)

    Knierim, James J.

    2006-01-01

    Place cells of the rat hippocampus are a dominant model system for understanding the role of the hippocampus in learning and memory at the level of single-unit and neural ensemble responses. A complete understanding of the information processing and computations performed by the hippocampus requires detailed knowledge about the properties of the…

  6. Nicotinic receptors in the dorsal and ventral hippocampus differentially modulate contextual fear conditioning.

    Science.gov (United States)

    Kenney, Justin W; Raybuck, Jonathan D; Gould, Thomas J

    2012-08-01

    Nicotine administration alters various forms of hippocampus-dependent learning and memory. Increasing work has found that the dorsal and ventral hippocampus differentially contribute to multiple behaviors. Thus, the present study examined whether the effects of nicotine in the dorsal and ventral hippocampus have distinct influences on contextual fear learning in male C57BL/6J mice. Direct infusion of nicotine into the dorsal hippocampus resulted in an enhancement of contextual fear learning, whereas nicotine infused into the ventral hippocampus resulted in deficits. Nicotine infusions into the ventral hippocampus did not alter hippocampus-independent cued fear conditioning or time spent in the open arm of the elevated plus maze, a measure of anxiety, suggesting that the effects are due to alterations in contextual learning and not other general processes. Finally, results from using direct infusions of MLA, a low-affinity α7 nicotinic acetylcholine receptor (nAChR) antagonist, in conjunction with systemic nicotine, provide evidence that α7-nAChRs in the ventral hippocampus mediate the detrimental effect of ventral hippocampal nicotine on contextual fear learning. These results suggest that with systemic nicotine administration, competition exists between the dorsal and ventral hippocampus for behavioral control over contextual learning. Copyright © 2012 Wiley Periodicals, Inc.

  7. Kaempferia parviflora rhizome extract and Myristica fragrans volatile oil increase the levels of monoamine neurotransmitters and impact the proteomic profiles in the rat hippocampus: Mechanistic insights into their neuroprotective effects

    Directory of Open Access Journals (Sweden)

    Waluga Plaingam

    2017-10-01

    Full Text Available Potentially useful in the treatment of neurodegenerative disorders, Kaempferia parviflora and Myristica fragrans have been shown to possess a wide spectrum of neuropharmacological activities and neuroprotective effects in vivo and in vitro. In this study, we determined whether and how K. parviflora ethanolic extract and M. fragrans volatile oil could influence the levels of neurotransmitters and the whole proteomic profile in the hippocampus of Sprague Dawley (SD rats. The effects of K. parviflora and M. fragrans on protein changes were analyzed by two-dimensional gel electrophoresis (2D-gel, and proteins were identified by liquid chromatography tandem mass spectrometry (LC-MS/MS. The target proteins were then confirmed by Western blot. The levels of neurotransmitters were evaluated by reversed-phase high-performance liquid chromatography (RP-HPLC. The results showed that K. parviflora, M. fragrans and fluoxetine (the control drug for this study increased serotonin, norepinephrine and dopamine in the rat hippocampus compared to that of the vehicle-treated group. Our proteomic data showed that 37 proteins in the K. parviflora group were up-regulated, while 14 were down-regulated, and 27 proteins in the M. fragrans group were up-regulated, while 16 were down-regulated. In the fluoxetine treatment group, we found 29 proteins up-regulated, whereas 14 proteins were down-regulated. In line with the proteomic data, the levels of GFAP, PDIA3, DPYSL2 and p-DPYSL2 were modified in the SD rat groups treated with K. parviflora, M. fragrans and fluoxetine as confirmed by Western blot. K. parviflora and M. fragrans mediated not only the levels of monoamine neurotransmitters but also the proteomic profiles in the rat hippocampus, thus shedding light on the mechanisms targeting neurodegenerative diseases.

  8. Surgical anatomy of the hippocampus.

    Science.gov (United States)

    Destrieux, C; Bourry, D; Velut, S

    2013-01-01

    Hippocampectomy is an efficient procedure for medial temporal lobe epilepsy. Nevertheless, hippocampus anatomy is complex, due to a deep location, and a complex structure. In this didactic paper, we propose a description of the hippocampus that should help neurosurgeons to feel at ease in this region. Embryological data was obtained from the literature, whereas adult anatomy was described after dissecting 8 human hemispheres (with and without vascular injection) and slicing 3 additional ones. The hippocampus is C-shaped and made of 2 rolled-up laminae, the cornu Ammonis and the gyrus dentatus. Its ventricular aspect is covered by the choroid plexus of the inferior horn excepted at the head level. Its cisternal aspect faces the mesencephalon from which it is limited by the transverse fissure. Its rostral part (head) curves dorso-caudally to form the uncus, located at the medial aspect of the temporal lobe. Its caudal part (tail) splits into the fimbria and the gyrus fasciolaris that respectively run ventral and dorsal to the corpus callosum, to become the fornix and indusium griseum. Consequences of this complex anatomy are presented, and the authors stress the need for a subpial resection. Important landmarks are provided to avoid lesions of the surrounding structures. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. Diapause prevention effect of Bombyx mori by dimethyl sulfoxide.

    Science.gov (United States)

    Yamamoto, Takayuki; Mase, Keisuke; Sawada, Hiroshi

    2013-01-01

    HCl treatment has been, for about 80 years, the primary method for the prevention of entry into embryonic diapauses of Bombyx mori. This is because no method is as effective as the HCl treatment. In this study, we discovered that dimethyl sulfoxide (DMSO) prevented entry into the diapause of the silkworm, Bombyx mori. The effect of diapause prevention was 78% as a result of treatment with 100% DMSO concentration, and the effect was comparable to that of the HCl treatment. In contrast, in the case of non-diapause eggs, hatchability was decreased by DMSO in a concentration-dependent manner. The effect of DMSO was restricted within 24 hours after oviposition of diapause eggs, and the critical period was slightly shorter than the effective period of the HCl treatment. DMSO analogs, such as dimethyl formamide (DMF) and dimethyl sulfide (DMS), did little preventive effect against the diapause. Furthermore, we also investigated the permeation effects of chemical compounds by DMSO. When treated with an inhibitor of protein kinase CK2 (CK2) dissolved in DMSO, the prevention rate of the diapause was less than 40%. This means that the inhibition effect by the CK2 inhibitor was the inhibition of embryonic development after diapause prevention by DMSO. These data suggest that DMSO has the effects of preventing from entering into the diapause and permeation of chemicals into diapause eggs.

  10. Diapause prevention effect of Bombyx mori by dimethyl sulfoxide.

    Directory of Open Access Journals (Sweden)

    Takayuki Yamamoto

    Full Text Available HCl treatment has been, for about 80 years, the primary method for the prevention of entry into embryonic diapauses of Bombyx mori. This is because no method is as effective as the HCl treatment. In this study, we discovered that dimethyl sulfoxide (DMSO prevented entry into the diapause of the silkworm, Bombyx mori. The effect of diapause prevention was 78% as a result of treatment with 100% DMSO concentration, and the effect was comparable to that of the HCl treatment. In contrast, in the case of non-diapause eggs, hatchability was decreased by DMSO in a concentration-dependent manner. The effect of DMSO was restricted within 24 hours after oviposition of diapause eggs, and the critical period was slightly shorter than the effective period of the HCl treatment. DMSO analogs, such as dimethyl formamide (DMF and dimethyl sulfide (DMS, did little preventive effect against the diapause. Furthermore, we also investigated the permeation effects of chemical compounds by DMSO. When treated with an inhibitor of protein kinase CK2 (CK2 dissolved in DMSO, the prevention rate of the diapause was less than 40%. This means that the inhibition effect by the CK2 inhibitor was the inhibition of embryonic development after diapause prevention by DMSO. These data suggest that DMSO has the effects of preventing from entering into the diapause and permeation of chemicals into diapause eggs.

  11. Effects of infrasound at 8 Hz 90 dB/130 dB on NMDAR1 expression and changes in intracellular calcium ion concentration in the hippocampus of rats.

    Science.gov (United States)

    Liu, Zhao-Hui; Chen, Jing-Zao; Ye, Lin; Liu, Jing; Qiu, Jian-Yong; Xu, Jian; Lu, Rui; Yuan, Xiao-Chao; Zhang, Wen-Dong; Li, Xiao-Fang; Li, Gong

    2010-01-01

    In the present study, we investigated the effect of infrasound on the expression of N-methyl-D-aspartate (NMDAR)1 as well as changes in intracellular calcium ion concentration ([Ca2+]i) in the hippocampus of rats. Sprague-Dawley (SD) rats were exposed for 2 h daily to infrasound at 8 Hz 90 dB or 130 dB, and NMDAR1 expression was examined on days 1, 7, 14, 21 and 28. The expression of NMDAR1 in the rat hippocampus upon exposure to infrasound at 8 Hz 90 dB sound pressure level (SPL) showed an initial decrease on day 1, an increase on days 7 and 14, a further decrease on day 21, and a return to normal levels on day 28. The peak level was observed on day 14 in every examined subregion of the hippocampus. By contrast, exposure to infrasound at 8 Hz 130 dB SPL had opposite effects, showing an increase on day 1, a decrease on day 7, a decrease to the lowest point on days 14, another increase on day 21 and a return to normal levels on day 28. The lowest expression of NMDAR1 was found in the CA1 and CA3 regions on day 14 and in the DG region on day 7 with exposure at 130 dB. There were significant differences in [Ca2+]i concentration on days 14 and 21 with infrasonic exposure at both 8 Hz 90 dB and 130 dB, but no significant differences in [Ca2+]i concentration on days 1, 7 and 28 compared to the control group. The highest [Ca2+]i level was noted on day 14 with infrasound exposure at 8 Hz 130 dB. These changes suggest that 8 Hz 90 dB/130 dB infrasound exposure induced certain reversible changes in NMDAR1 expression and [Ca2+]i concentration in hippocampal cells, which may influence mnemonic functions related to the hippocampus.

  12. The economic effect of Planet Health on preventing bulimia nervosa.

    Science.gov (United States)

    Wang, Li Yan; Nichols, Lauren P; Austin, S Bryn

    2011-08-01

    To assess the economic effect of the school-based obesity prevention program Planet Health on preventing disordered weight control behaviors and to determine the cost-effectiveness of the intervention in terms of its combined effect on prevention of obesity and disordered weight control behaviors. On the basis of the intervention's short-term effect on disordered weight control behaviors prevention, we projected the number of girls who were prevented from developing bulimia nervosa by age 17 years. We further estimated medical costs saved and quality-adjusted life years gained by the intervention over 10 years. As a final step, we compared the intervention costs with the combined intervention benefits from both obesity prevention (reported previously) and prevention of disordered weight control behaviors to determine the overall cost-effectiveness of the intervention. Middle schools. A sample of 254 intervention girls aged 10 to 14 years. The Planet Health program was implemented during the school years from 1995 to 1997 and was designed to promote healthful nutrition and physical activity among youth. Intervention costs, medical costs saved, quality-adjusted life years gained, and cost-effectiveness ratio. An estimated 1 case of bulimia nervosa would have been prevented. As a result, an estimated $33 999 in medical costs and 0.7 quality-adjusted life years would be saved. At an intervention cost of $46 803, the combined prevention of obesity and disordered weight control behaviors would yield a net savings of $14 238 and a gain of 4.8 quality-adjusted life years. Primary prevention programs, such as Planet Health, warrant careful consideration by policy makers and program planners. The findings of this study provide additional argument for integrated prevention of obesity and eating disorders.

  13. Aging, stress and the hippocampus.

    Science.gov (United States)

    Miller, D B; O'Callaghan, J P

    2005-05-01

    Functional loss often occurs in many body systems (e.g., endocrine, cognitive, motor) with the passage of years, but there is great individual variation in the degree of compromise shown. The current focus on brain aging will continue because demographic trends indicate that the average lifespan will show a continued increase. There is increasing emphasis on understanding how aging contributes to a decline in brain functions, cognition being a prime example. This is due in part to the fact that dementias and other losses in brain function that sometimes accompany aging cause an obvious decline in the quality of life and these deficits are of more concern as the number of elderly increase. Stress also is a ubiquitous aspect of life and there is now a greater interest in understanding the role of stress and the stress response in brain aging. The key role of the hippocampus and its related brain structures in cognition, as well as in the feedback control of the response to stress, have made this brain area a logical focus of investigation for those interested in the impact of stress on brain aging. Here, we describe how the hippocampus changes with age and we examine the idea that age-related changes in the secretion patterns of the hypothalamic-pituitary adrenal (HPA) axis can contribute to aging of this structure. We also examine the proposal that stress, perhaps due to compromised HPA axis function, can contribute to hippocampal aging through exposure to excessive levels of glucocorticoids. The aging hippocampus does not appear to suffer a generalized loss of cells or synapses, although atrophy of the structure may occur in humans. Thus, age-related cognitive impairments are likely related to other neurobiological alterations that could include changes in the signaling, information encoding, plasticity, electrophysiological or neurochemical properties of neurons or glia. Although excessive levels of glucocorticoids are able to interfere with cognition, as well as

  14. Effect of the N-methyl-D-aspartate NR2B subunit antagonist ifenprodil on precursor cell proliferation in the hippocampus.

    Science.gov (United States)

    Bunk, E C; König, H-G; Prehn, J H M; Kirby, B P

    2014-06-01

    The N-methyl-D-aspartate (NMDA) receptor, one of the ionotropic glutamate receptor, plays important physiological and pathological roles in learning and memory, neuronal development, acute and chronic neurological diseases, and neurogenesis. This work examines the contribution of the NR2B NMDA receptor subunit to adult neurogenesis/cell proliferation under physiological conditions and following an excitotoxic insult. We have previously shown in vitro that a discrete NMDA-induced, excitotoxic injury to the hippocampus results in an increase in neurogenesis within the dentate gyrus. Here we have characterized adult neurogenesis or proliferation, using BrdU, in an in vivo model of excitotoxic injury to the CA1 subfield of the hippocampus. We demonstrate a peak in neural stem cell proliferation/neurogenesis between 6 and 9 days after the excitotoxic insult. Treatment with ifenprodil, an NR2B subunit-specific NMDA receptor antagonist, without prior injury induction, also increased the number of BrdU-positive cells within the DG and posterior periventricle, indicating that ifenprodil itself could modulate the rate of proliferation. Interestingly, though, the increased level of cell proliferation did not change significantly when ifenprodil was administered following an excitotoxic insult. In conclusion, our results suggest and add to the growing evidence that NR2B subunit-containing NMDA receptors play a role in neural stem cell proliferation. Copyright © 2014 Wiley Periodicals, Inc.

  15. The effect of intra-ventral hippocampus administration of TRPV1 agonist and antagonist on spatial learning and memory in male rats.

    Science.gov (United States)

    Amiresmaili, Sedigheh; Shamsizadeh, Ali; Allahtavakoli, Mohammad; Pourshanazari, Ali Asghar; Roohbakhsh, Ali

    2014-02-01

    The role of transient receptor potential vanilloid 1 (TRPV1) in peripheral nervous system has been studied well but its role in the central nervous system remains to be studied in detail. The expression of TRPV1 receptors in hippocampus is suggesting that they may play an important role in higher cognitive functions such as learning and memory. In the present study, the role of TRPV1 receptors in acquisition and retrieval of spatial memory of male Wistar rats was evaluated by intra-ventral hippocampus administration of TRPV1 selective agonist (OLDA) and antagonist (AMG9810) using Morris water maze. The results demonstrated that administration of either OLDA (0.001, 0.01 and 0.1 μg/rat) or AMG9810 (0.003, 0.03 and 0.3 μg/rat) did not influence memory acquisition or retrieval. These data suggest that ventral-hippocampal TRPV1 receptors possibly are not involved in spatial learning and memory. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  16. Child sexual abuse: prevalence, effects and school based prevention

    OpenAIRE

    Ayşe Rezan Çeçen

    2007-01-01

    Child sexual abuse is a complex and serious phenomenon that causes short and long term debilitating effects on individuals and their quality of life and life satisfaction. Last three decades child sexual abuse (prevalence, effects and prevention methods) has been very important multidisciplinary topic in academic field in North American developed countries but In our country, Turkey there are not sufficient studies related to prevalence, effects and prevention of child sexual abuse. In this s...

  17. Child Sexual Abuse Prevention Programs: Effects on Early Identification.

    Science.gov (United States)

    Ullman, Douglas G.; And Others

    The number of child sexual abuse prevention programs incorporated into school curricula has increased steadily in the past decade. This longitudinal study evaluated the effects of a school-based, child sexual abuse prevention program on child abuse reports in nine school districts over a five-year period. Districts had been randomly assigned to…

  18. Assessment of Effective Coverage of HIV Prevention of Pregnant ...

    African Journals Online (AJOL)

    BACKGROUND: Coverage assessment of prevention of Pregnant Mother to Child Transmission (PMTCT) of HIV service is useful to measure the health system effort or performance of health service delivery function and to influence decisions. The objective of this study was to assess effective coverage level for prevention ...

  19. Post-Training Reversible Inactivation of the Hippocampus Enhances Novel Object Recognition Memory

    Science.gov (United States)

    Oliveira, Ana M. M.; Hawk, Joshua D.; Abel, Ted; Havekes, Robbert

    2010-01-01

    Research on the role of the hippocampus in object recognition memory has produced conflicting results. Previous studies have used permanent hippocampal lesions to assess the requirement for the hippocampus in the object recognition task. However, permanent hippocampal lesions may impact performance through effects on processes besides memory…

  20. Spatial memory and the monkey hippocampus: not all space is created equal.

    Science.gov (United States)

    Banta Lavenex, Pamela; Lavenex, Pierre

    2009-01-01

    Studies of the role of the monkey hippocampus in spatial learning and memory, however few, have reliably produced inconsistent results. Whereas the role of the hippocampus in spatial learning and memory has been clearly established in rodents, studies in nonhuman primates have made a variety of claims that range from the involvement of the hippocampus in spatial memory only at relatively longer memory delays, to no role for the hippocampus in spatial memory at all. In contrast, we have shown that selective damage restricted to the hippocampus (CA regions) prevents the learning or use of allocentric, spatial relational representations of the environment in freely behaving adult monkeys tested in an open-field arena. In this commentary, we discuss a unifying framework that explains these apparently discrepant results regarding the role of the monkey hippocampus in spatial learning and memory. We describe clear and strict criteria to interpret the findings from previous studies and guide future investigations of spatial memory in monkeys. Specifically, we affirm that, as in the rodent, the primate hippocampus is critical for spatial relational learning and memory, and in a time-independent manner. We describe how claims to the contrary are the result of experimental designs that fail to recognize, and control for, egocentric (hippocampus-independent) and allocentric (hippocampus-dependent) spatial frames of reference. Finally, we conclude that the available data demonstrate unequivocally that the central role of the hippocampus in allocentric, spatial relational learning and memory is conserved among vertebrates, including nonhuman primates. Copyright 2008 Wiley-Liss, Inc.

  1. Hippocampus Segmentation Based on Local Linear Mapping

    Science.gov (United States)

    Pang, Shumao; Jiang, Jun; Lu, Zhentai; Li, Xueli; Yang, Wei; Huang, Meiyan; Zhang, Yu; Feng, Yanqiu; Huang, Wenhua; Feng, Qianjin

    2017-04-01

    We propose local linear mapping (LLM), a novel fusion framework for distance field (DF) to perform automatic hippocampus segmentation. A k-means cluster method is propose for constructing magnetic resonance (MR) and DF dictionaries. In LLM, we assume that the MR and DF samples are located on two nonlinear manifolds and the mapping from the MR manifold to the DF manifold is differentiable and locally linear. We combine the MR dictionary using local linear representation to present the test sample, and combine the DF dictionary using the corresponding coefficients derived from local linear representation procedure to predict the DF of the test sample. We then merge the overlapped predicted DF patch to obtain the DF value of each point in the test image via a confidence-based weighted average method. This approach enabled us to estimate the label of the test image according to the predicted DF. The proposed method was evaluated on brain images of 35 subjects obtained from SATA dataset. Results indicate the effectiveness of the proposed method, which yields mean Dice similarity coefficients of 0.8697, 0.8770 and 0.8734 for the left, right and bi-lateral hippocampus, respectively.

  2. Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) Promotes Hippocampus-Dependent Memory via Its Deubiquitinating Effect on TrkB.

    Science.gov (United States)

    Guo, Yun-Yun; Lu, Yi; Zheng, Yuan; Chen, Xiao-Rong; Dong, Jun-Lu; Yuan, Rong-Rong; Huang, Shu-Hong; Yu, Hui; Wang, Yue; Chen, Zhe-Yu; Su, Bo

    2017-06-21

    Multiple studies have established that brain-derived neurotrophic factor (BDNF) plays a critical role in the regulation of synaptic plasticity via its receptor, TrkB. In addition to being phosphorylated, TrkB has also been demonstrated to be ubiquitinated. However, the mechanisms of TrkB ubiquitination and its biological functions remain poorly understood. In this study, we demonstrate that ubiquitin C-terminal hydrolase L1 (UCH-L1) promotes contextual fear conditioning learning and memory via the regulation of ubiquitination of TrkB. We provide evidence that UCH-L1 can deubiquitinate TrkB directly. K460 in the juxtamembane domain of TrkB is the primary ubiquitination site and is regulated by UCH-L1. By using a peptide that competitively inhibits the association between UCH-L1 and TrkB, we show that the blockade of UCH-L1-regulated TrkB deubiquitination leads to increased BDNF-induced TrkB internalization and consequently directs the internalized TrkB to the degradation pathway, resulting in increased degradation of surface TrkB and attenuation of TrkB activation and its downstream signaling pathways. Moreover, injection of the peptide into the DG region of mice impairs hippocampus-dependent memory. Together, our results suggest that the ubiquitination of TrkB is a mechanism that controls its downstream signaling pathways via the regulation of its endocytosis and postendocytic trafficking and that UCH-L1 mediates the deubiquitination of TrkB and could be a potential target for the modulation of hippocampus-dependent memory.SIGNIFICANCE STATEMENT Ubiquitin C-terminal hydrolase L1 (UCH-L1) has been demonstrated to play important roles in the regulation of synaptic plasticity and learning and memory. TrkB, the receptor for brain-derived neurotrophic factor, has also been shown to be a potent regulator of synaptic plasticity. In this study, we demonstrate that UCH-L1 functions as a deubiquitinase for TrkB. The blockage of UCH-L1-regulated deubiquitination of Trk

  3. microRNA targeting of the P2X7 purinoceptor opposes a contralateral epileptogenic focus in the hippocampus

    Science.gov (United States)

    Jimenez-Mateos, Eva M.; Arribas-Blazquez, Marina; Sanz-Rodriguez, Amaya; Concannon, Caoimhin; Olivos-Ore, Luis A.; Reschke, Cristina R.; Mooney, Claire M.; Mooney, Catherine; Lugara, Eleonora; Morgan, James; Langa, Elena; Jimenez-Pacheco, Alba; Silva, Luiz Fernando Almeida; Mesuret, Guillaume; Boison, Detlev; Miras-Portugal, M. Teresa; Letavic, Michael; Artalejo, Antonio R.; Bhattacharya, Anindya; Diaz-Hernandez, Miguel; Henshall, David C.; Engel, Tobias

    2015-01-01

    The ATP-gated ionotropic P2X7 receptor (P2X7R) modulates glial activation, cytokine production and neurotransmitter release following brain injury. Levels of the P2X7R are increased in experimental and human epilepsy but the mechanisms controlling P2X7R expression remain poorly understood. Here we investigated P2X7R responses after focal-onset status epilepticus in mice, comparing changes in the damaged, ipsilateral hippocampus to the spared, contralateral hippocampus. P2X7R-gated inward currents were suppressed in the contralateral hippocampus and P2rx7 mRNA was selectively uploaded into the RNA-induced silencing complex (RISC), suggesting microRNA targeting. Analysis of RISC-loaded microRNAs using a high-throughput platform, as well as functional assays, suggested the P2X7R is a target of microRNA-22. Inhibition of microRNA-22 increased P2X7R expression and cytokine levels in the contralateral hippocampus after status epilepticus and resulted in more frequent spontaneous seizures in mice. The major pro-inflammatory and hyperexcitability effects of microRNA-22 silencing were prevented in P2rx7−/− mice or by treatment with a specific P2X7R antagonist. Finally, in vivo injection of microRNA-22 mimics transiently suppressed spontaneous seizures in mice. The present study supports a role for post-transcriptional regulation of the P2X7R and suggests therapeutic targeting of microRNA-22 may prevent inflammation and development of a secondary epileptogenic focus in the brain. PMID:26631939

  4. Making context memories independent of the hippocampus

    OpenAIRE

    Lehmann, Hugo; Sparks, Fraser T.; Spanswick, Simon C.; Hadikin, Crystal; McDonald, Robert. J.; Sutherland, Robert J.

    2009-01-01

    We present evidence that certain learning parameters can make a memory, even a very recent one, become independent of the hippocampus. We confirm earlier findings that damage to the hippocampus causes severe retrograde amnesia for context memories, but we show that repeated learning sessions create a context memory that is not vulnerable to the damage. The findings demonstrate that memories normally dependent on the hippocampus are incrementally strengthened in other memory networks with addi...

  5. Insulin-Like Growth Factor I Produces an Antidepressant-Like Effect and Elicits N-Methyl-D-Aspartate Receptor Independent Long-Term Potentiation of Synaptic Transmission in Medial Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    Burgdorf, Jeffrey; Zhang, Xiao-lei; Colechio, Elizabeth M; Ghoreishi-Haack, Nayereh; Gross, Amanda; Kroes, Roger A; Stanton, Patric K; Moskal, Joseph R

    2015-09-15

    Growth factors play an important role in regulating neurogenesis and synapse formation and may be involved in regulating the antidepressant response to conventional antidepressants. To date, Insulin-like growth factor I (IGFI) is the only growth factor that has shown antidepressant properties in human clinical trials. However, its mechanism of action remains unclear. The antidepressant-like effect of a single IV dose of IGFI was determined using a chronic unpredictable stress paradigm in the rat Porsolt, sucrose preference, novelty-induced hypophagia, and ultrasonic vocalization models. The dependence of the medial prefrontal cortex for these effects was determined by direct medial prefrontal cortex injection followed by Porsolt testing as well as IGFI receptor activation in the medial prefrontal cortex following an optimal IV antidepressant-like dose of IGFI. The effect of IGFI on synaptic transmission and long-term potentiation (LTP) of synaptic strength was assessed in the hippocampus and medial prefrontal cortex. The dependence of these effects on IGFI and AMPA receptor activation and protein synthesis were also determined. IGFI produced a rapid-acting and long-lasting antidepressant-like effect in each of the depression models. These effects were blocked by IGFI and AMPA receptor antagonists, and medial prefrontal cortex was localized. IGFI robustly increased synaptic strength in the hippocampus and medial prefrontal cortex and these effects were IGFI receptor and protein synthesis-dependent but N-methyl-d-aspartate receptor independent. IGFI also robustly facilitated hippocampal metaplasticity 24 hours postdosing. These data support the conclusion that the antidepressant-like effects of IGFI are mediated by a persistent, LTP-like enhancement of synaptic strength requiring both IGFIR activation and ongoing protein synthesis. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  6. Preventive Effects of Cocoa and Cocoa Antioxidants in Colon Cancer

    National Research Council Canada - National Science Library

    Martín, María; Goya, Luis; Ramos, Sonia

    2016-01-01

    ... of initiated and malignant cells. Therefore, restriction of oxidative stress and/or prevention or delayed progression of cancer stages by cocoa antioxidant compounds has gained interest as an effective...

  7. Effective HIV prevention: the indispensable role of social science

    Directory of Open Access Journals (Sweden)

    Susan Kippax

    2012-04-01

    Full Text Available This paper examines the ways in which HIV prevention is understood including “biomedical”, “behavioural”, “structural”, and “combination” prevention. In it I argue that effective prevention entails developing community capacity and requires that public health addresses people not only as individuals but also as connected members of groups, networks and collectives who interact (talk, negotiate, have sex, use drugs, etc. together. I also examine the evaluation of prevention programmes or interventions and argue that the distinction between efficacy and effectiveness is often glossed and that, while efficacy can be evaluated by randomized controlled trials, the evaluation of effectiveness requires long-term descriptive strategies and/or modelling. Using examples from a number of countries, including a detailed account of the Australian HIV prevention response, effectiveness is shown to be dependent not only on the efficacy of the prevention technology or tool but also on the responses of people – individuals, communities and governments – to those technologies. Whether a particular HIV prevention technology is adopted and its use sustained depends on a range of social, cultural and political factors. The paper concludes by calling on biomedical and social scientists to work together and describes a “social public health”.

  8. The Role of Glucocorticoid Receptors in Dexamethasone-Induced Apoptosis of Neuroprogenitor Cells in the Hippocampus of Rat Pups

    Directory of Open Access Journals (Sweden)

    Chun-I Sze

    2013-01-01

    Full Text Available Background. Dexamethasone (Dex has been used to reduce inflammation in preterm infants with assistive ventilation and to prevent chronic lung diseases. However, Dex treatment results in adverse effects on the brain. Since the hippocampus contains a high density of glucocorticoid receptors (GCRs, we hypothesized that Dex affects neurogenesis in the hippocampus through inflammatory mediators. Methods. Albino Wistar rat pups first received a single dose of Dex (0.5 mg/kg on postnatal day 1 (P1 and were sacrificed on P2, P3, P5, and P7. One group of Dex-treated pups (Dex-treated D1D2 was given mifepristone (RU486, a GCR antagonist on P1 and sacrificed on P2. Hippocampi were isolated for western blot analysis, TUNEL, cleaved-caspase 3 staining for cell counts, and morphological assessment. Control pups received normal saline (NS. Results. Dex reduced the developmental gain in body weight, but had no effect on brain weight. In the Dex-treated D1D2 group, apoptotic cells increased in number based on TUNEL and cleaved-caspase 3 staining. Most of the apoptotic cells expressed the neural progenitor cell marker nestin. Dex-induced apoptosis in P1 pups was markedly reduced (60% by pretreatment with RU486, indicating the involvement of GCRs. Conclusion. Early administration of Dex results in apoptosis of neural progenitor cells in the hippocampus and this is mediated through GCRs.

  9. Ensuring effective prevention of iodine-deficiency disorders

    DEFF Research Database (Denmark)

    Völzke, Henry; Caron, Philippe Jean; Dahl, Lisbeth

    2016-01-01

    BACKGROUND: Programs initiated to prevent iodine deficiency disorders (IDD) may not remain effective due to changes in government policies, commercial factors, and human behavior that may affect the efficacy of IDD prevention programs in unpredictable directions. Monitoring and outcome studies...... are needed to optimize the effectiveness of IDD prevention. SUMMARY: Although the need for monitoring is compelling, the current reality in Europe is less than optimal. Regular and systematic monitoring surveys have only been established in a few countries, and comparability across the studies is hampered...... by the lack of centralized standardization procedures. In addition, data on outcomes and the cost of achieving them are needed in order to provide evidence of the beneficial effects of IDD prevention in countries with mild iodine deficiency. CONCLUSION: Monitoring studies can be optimized by including...

  10. Nicotine-induced neuroplasticity counteracts the effect of schizophrenia-linked neuregulin 1 signaling on NMDAR function in the rat hippocampus.

    Science.gov (United States)

    Yamazaki, Yoshihiko; Sumikawa, Katumi

    2017-02-01

    A high rate of heavy tobacco smoking among people with schizophrenia has been suggested to reflect self-medication and amelioration of cognitive dysfunction, a core feature of schizophrenia. NMDAR hypofunction is hypothesized to be a mechanism of cognitive dysfunction, and excessive schizophrenia-linked neuregulin 1 (NRG1) signaling through its receptor ErbB4 can suppress NMDAR function by preventing Src-mediated enhancement of NMDAR responses. Here we investigated whether chronic nicotine exposure in rats by subcutaneous injection of nicotine (0.5-1 mg/kg, twice daily for 10-15 days) counteracts the suppressive effect of NRG1β on NMDAR-mediated responses recorded from CA1 pyramidal cells in acute hippocampal slices. We found that NRG1β, which prevents the enhancement of NMDAR responses by the Src-family-kinase-activating peptide pYEEI in naive rats, failed to block the effect of pYEEI in nicotine-exposed rats. In naive rats, NRG1β acts only on GluN2B-NMDARs by blocking their Src-mediated upregulation. Chronic nicotine exposure causes enhanced GluN2B-NMDAR responses via Src upregulation and recruits Fyn for the enhancement of GluN2A-NMDAR responses. NRG1β has no effect on both enhanced basal GluN2B-NMDAR responses and Fyn-mediated enhancement of GluN2A-NMDAR responses. Src-mediated enhancement of GluN2B-NMDAR responses and Fyn-mediated enhancement of GluN2A-NMDAR responses initiate long-term potentiation (LTP) of AMPAR synaptic responses in naive and nicotine-exposed CA1 pyramidal cells, respectively. These results suggest that NRG1β suppresses LTP by blocking Src-mediated enhancement of GluN2B-NMDAR responses, but has no effect on LTP in nicotine-exposed rats. These effects of chronic nicotine exposure may counteract the negative effect of increased NRG1-ErbB4 signaling on the cellular mechanisms of learning and memory in individuals with schizophrenia, and therefore may motivate heavy smoking. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Effect of chloramine-T on long-term potentiation at synapses between perforant path and dentate gyrus in hippocampus of rats in vivo.

    Science.gov (United States)

    Yang, Jun; Hu, Zhuang-Li; Jiang, Bo; Ni, Lan; Jin, You; Chen, Jian-Guo; Wang, Fang

    2011-03-01

    Reactive oxygen species (ROS), including superoxide, are generally considered as neurotoxic molecules whose effects can be alleviated by antioxidant enzymes. However, ROS also are known to be necessary components of the signal transduction cascades underlying normal synaptic plasticity. The oxidant chloramine-T (Ch-T), a specific oxidant to sulphur-containing residues, can oxidize methionine (Met) residues in proteins to alter protein function. To investigate the effect of Ch-T on the induction of hippocampal long-term potentiation (LTP) in dentate gyrus (DG), in vivo electrophysiological recording was employed. It was found that intracerebroventricular (ICV) injection of 0.1 μM Ch-T in 5 μL enhanced hippocampal LTP of rats slightly, whereas, 20 mM Ch-T in 5 μL greatly attenuated LTP. These effects can be reversed by pretreatment with 0.1 mM dithiothretol (DTT), a special thiol reductant. In addition, 0.1 μM Ch-T elevated LTP-induced increase in phosphorylation of Ca²+/calmodulin (CaM)-dependent protein kinase (CaMKII) and neurogranin (Ng), whereas 2 μM and 20 mM Ch-T reduced LTP-induced increase in phosphorylation status of the two key proteins, especially for 20 mM Ch-T. Pretreatment with DTT significantly prevented these effects. Taken together, these findings demonstrated that Ch-T has concentration-dependent effects on the induction of hippocampal LTP in vivo. In brief, low concentration of Ch-T facilitated hippocampal LTP by enhancing LTP-induced increase in p-CaMKII and p-Ng compared to controls, whereas high concentration of Ch-T obviously attenuated LTP accompanied by a decrease in the phosphorylated proteins, and both of these effects can be prevented by DTT. These results indicate that Ch-T modulates hippocampal LTP through regulating phosphorylation status of CaMKII and Ng. Published by Elsevier B.V.

  12. Prevention

    DEFF Research Database (Denmark)

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  13. Clinical correlates of hippocampus volume and shape in antipsychotic-naïve schizophrenia.

    Science.gov (United States)

    Kalmady, Sunil Vasu; Shivakumar, Venkataram; Arasappa, Rashmi; Subramaniam, Aditi; Gautham, S; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

    2017-05-30

    While volume deficit of hippocampus is an established finding in schizophrenia, very few studies have examined large sample of patients without the confounding effect of antipsychotic treatment. Concurrent evaluation of hippocampus shape will offer additional information on the hippocampal aberrations in schizophrenia. In this study, we analyzed the volume and shape of hippocampus in antipsychotic-naïve schizophrenia patients (N=71) in comparison to healthy controls (N=82). Using 3-T MRI data, gray matter (GM) volume (anterior and posterior sub-divisions) and shape of the hippocampus were analyzed. Schizophrenia patients had significant hippocampal GM volume deficits (specifically the anterior sub-division) in comparison to healthy controls. There were significant positive correlations between anterior hippocampus volume and psychopathology scores of positive syndrome. Shape analyses revealed significant inward deformation of bilateral hippocampal surface in patients. In conclusion, our study findings add robust support for volume deficit in hippocampus in antipsychotic-naïve schizophrenia. Hippocampal shape deficits in schizophrenia observed in this study map to anterior CA1 sub-region. The differential relationship of anterior hippocampus (but not posterior hippocampus) with clinical symptoms is in tune with the findings in animal models. Further systematic studies are needed to evaluate the relationship between these hippocampal gray matter deficits with white matter and functional connectivity to facilitate understanding the hippocampal network abnormalities in schizophrenia. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  14. Agomelatine, venlafaxine, and running exercise effectively prevent anxiety- and depression-like behaviors and memory impairment in restraint stressed rats.

    Science.gov (United States)

    Lapmanee, Sarawut; Charoenphandhu, Jantarima; Teerapornpuntakit, Jarinthorn; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2017-01-01

    Several severe stressful situations, e.g., natural disaster, infectious disease out break, and mass casualty, are known to cause anxiety, depression and cognitive impairment, and preventive intervention for these stress complications is worth exploring. We have previously reported that the serotonin-norepinephrine-dopamine reuptake inhibitor, venlafaxine, as well as voluntary wheel running are effective in the treatment of anxiety- and depression-like behaviors in stressed rats. But whether they are able to prevent deleterious consequences of restraint stress in rats, such as anxiety/depression-like behaviors and memory impairment that occur afterward, was not known. Herein, male Wistar rats were pre-treated for 4 weeks with anti-anxiety/anti-depressive drugs, agomelatine and venlafaxine, or voluntary wheel running, followed by 4 weeks of restraint-induced stress. During the stress period, rats received neither drug nor exercise intervention. Our results showed that restraint stress induced mixed anxiety- and depression-like behaviors, and memory impairment as determined by elevated plus-maze, elevated T-maze, open field test (OFT), forced swimming test (FST), and Morris water maze (MWM). Both pharmacological pre-treatments and running successfully prevented the anxiety-like behavior, especially learned fear, in stressed rats. MWM test suggested that agomelatine, venlafaxine, and running could prevent stress-induced memory impairment, but only pharmacological treatments led to better novel object recognition behavior and positive outcome in FST. Moreover, western blot analysis demonstrated that venlafaxine and running exercise upregulated brain-derived neurotrophic factor (BDNF) expression in the hippocampus. In conclusion, agomelatine, venlafaxine as well as voluntary wheel running had beneficial effects, i.e., preventing the restraint stress-induced anxiety/depression-like behaviors and memory impairment.

  15. Agomelatine, venlafaxine, and running exercise effectively prevent anxiety- and depression-like behaviors and memory impairment in restraint stressed rats.

    Directory of Open Access Journals (Sweden)

    Sarawut Lapmanee

    Full Text Available Several severe stressful situations, e.g., natural disaster, infectious disease out break, and mass casualty, are known to cause anxiety, depression and cognitive impairment, and preventive intervention for these stress complications is worth exploring. We have previously reported that the serotonin-norepinephrine-dopamine reuptake inhibitor, venlafaxine, as well as voluntary wheel running are effective in the treatment of anxiety- and depression-like behaviors in stressed rats. But whether they are able to prevent deleterious consequences of restraint stress in rats, such as anxiety/depression-like behaviors and memory impairment that occur afterward, was not known. Herein, male Wistar rats were pre-treated for 4 weeks with anti-anxiety/anti-depressive drugs, agomelatine and venlafaxine, or voluntary wheel running, followed by 4 weeks of restraint-induced stress. During the stress period, rats received neither drug nor exercise intervention. Our results showed that restraint stress induced mixed anxiety- and depression-like behaviors, and memory impairment as determined by elevated plus-maze, elevated T-maze, open field test (OFT, forced swimming test (FST, and Morris water maze (MWM. Both pharmacological pre-treatments and running successfully prevented the anxiety-like behavior, especially learned fear, in stressed rats. MWM test suggested that agomelatine, venlafaxine, and running could prevent stress-induced memory impairment, but only pharmacological treatments led to better novel object recognition behavior and positive outcome in FST. Moreover, western blot analysis demonstrated that venlafaxine and running exercise upregulated brain-derived neurotrophic factor (BDNF expression in the hippocampus. In conclusion, agomelatine, venlafaxine as well as voluntary wheel running had beneficial effects, i.e., preventing the restraint stress-induced anxiety/depression-like behaviors and memory impairment.

  16. Enhanced dendritic spine number of neurons of the prefrontal cortex, hippocampus and nucleus accumbens in old rats after chronic donepezil administration

    Science.gov (United States)

    Alcantara-Gonzalez, Faviola; Juarez, Ismael; Solis, Oscar; Martinez-Tellez, Isaura; Camacho-Abrego, Israel; Masliah, Eliezer; Mena, Raul; Flores, Gonzalo

    2010-01-01

    In Alzheimer's disease brains morphological changes in the dendrites of pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been observed. These changes are particularly reflected in the decrement of both the dendritic tree and spine number. Donepezil is a potent and selective acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease. We have studied the effect of oral administration of this drug on the morphology of neuronal cells from the brain of aged rats. We examined dendrites of pyramidal neurons of the PFC, dorsal or ventral hippocampus and medium spiny neurons of the nucleus accumbens (NAcc). Donepezil (1 mg/Kg, vo) was administrated every day for 60 days to rats aged 10 and 18 months. Dendritic morphology was studied by the Golgi-Cox stain procedure followed by Sholl analysis at 12 and 20 months ages, respectively. In all Donepezil treated-rats a significant increment of the dendritic spines number in pyramidal neurons of the PFC, dorsal hippocampus was observed. However, pyramidal neurons of the ventral hippocampus and medium spiny cells of the NAcc only showed an increase in the number of their spines in 12 months old-rats. Our results suggest that Donepezil prevents the alterations of the neuronal dendrite morphology caused by aging. PMID:20336627

  17. Hippocampus and amygdalar volumes in patients with somatization disorder.

    Science.gov (United States)

    Atmaca, Murad; Sirlier, Burcu; Yildirim, Hanefi; Kayali, Alperen

    2011-08-15

    In regard to somatization disorder which covers an important section of our patient population, there is no systematic structural magnetic resonance imaging (MRI) study in the literature. Therefore, we aimed to use structural MRI to evaluate the hippocampus amygdalar complex which is associated with both stress and regulation of emotion that are main basis clinical presentation of somatization disorder in the patients with somatization disorder. Totally 40 subjects (20 patients with somatization disorder and 20 healthy controls) were enrolled. Intracranial volume (ICV), whole brain volume, gray and white matter volumes, and hippocampus and amygdalar volumes of the subjects were measured. In regard to unadjusted mean volumes of measured structures, the patients had significantly smaller mean volumes of the left and right amygdala. However, two groups did not differ significantly in terms of whole brain, total gray and white matter or hippocampus volumes. The repeated measures ANCOVA predicting left and right amygdala volumes demonstrated a significant main effect of diagnostic group. In conclusion, the findings of the present study revealed that the patients with somatization disorder had significantly smaller mean volumes of the left and right amygdala without any differences in regard to whole brain, total gray and white matter or hippocampus volumes. On the basis of the current findings, it seems reasonable to evaluate that abnormalities in connectivity and/or metabolism dimensions and to examine the effects of drugs or psychotherapeutic approaches could be especially informative. Copyright © 2011. Published by Elsevier Inc.

  18. The role of the avian hippocampus in spatial memory

    Directory of Open Access Journals (Sweden)

    Euan M. Macphail

    2002-01-01

    Full Text Available Avian hippocampal function is surveyed, using data drawn from three areas: conventional laboratory paradigms, pigeon navigation, and food-storing. Damage to the avian hippocampus disrupts performance in laboratory tasks that tap spatial learning and memory, and also disrupts both pigeon homing and cache recovery by food-storing birds. Further evidence of hippocampal involvement in food-storing is provided by the fact that the hippocampus of food-storing birds is selectively enlarged. These findings lend support to the notion that the hippocampus plays a critical role in spatial learning and memory. However, avian hippocampal lesions (like mammalian hippocampal lesions also disrupt certain laboratory tasks that do not have an overt spatial component. Moreover, analysis of the effects of hippocampal lesions on navigation find, first, that basic navigational processes are left intact, and second, that at least some of the disruption of homing may be caused by disruption of the associability of information derived from the sun compass - a non-spatial deficit. Finally, attempts to demonstrate that the enlarged hippocampus of food-storing birds is associated with enhanced spatial memory have failed to deliver conclusive support. The extensive parallels between effects of hippocampal lesions in birds and mammals suggest that both the spatial and the non-spatial deficits form part of a single syndrome, one that cannot readily be explained in terms of disruption of specifically spatial processes.

  19. Sleep selectively enhances hippocampus-dependent memory in mice.

    Science.gov (United States)

    Cai, Denise J; Shuman, Tristan; Gorman, Michael R; Sage, Jennifer R; Anagnostaras, Stephan G

    2009-08-01

    Sleep has been implicated as playing a critical role in memory consolidation. Emerging evidence suggests that reactivation of memories during sleep may facilitate the transfer of declarative memories from the hippocampus to the neocortex. Previous rodent studies have utilized sleep-deprivation to examine the role of sleep in memory consolidation. The present study uses a novel, naturalistic paradigm to study the effect of a sleep phase on rodent Pavlovian fear conditioning, a task with both hippocampus-dependent and -independent components (contextual vs. cued memories). Mice were trained 1 hour before their sleep/rest phase or awake/active phase and then tested for contextual and cued fear 12 or 24 hr later. The authors found that hippocampus-dependent contextual memory was enhanced if tested after a sleep phase within 24 hr of training. This enhancement was specific to context, not cued, memory. These findings provide direct evidence of a role for sleep in enhancing hippocampus-dependent memory consolidation in rodents and detail a novel paradigm for examining sleep-induced memory effects. 2009 APA, all rights reserved

  20. Loss of Parvalbumin in the Hippocampus of MAM Schizophrenia Model Rats Is Attenuated by Peripubertal Diazepam.

    Science.gov (United States)

    Du, Yijuan; Grace, Anthony A

    2016-11-01

    Loss of parvalbumin interneurons in the hippocampus is a robust finding in schizophrenia brains. Rats exposed during embryonic day 17 to methylazoxymethanol acetate exhibit characteristics consistent with an animal model of schizophrenia, including decreased parvalbumin interneurons in the ventral hippocampus. We reported previously that peripubertal administration of diazepam prevented the emergence of pathophysiology in adult methylazoxymethanol acetate rats. We used an unbiased stereological method to examine the impact of peripubertal diazepam treatment on parvalbumin interneuron number in the ventral subiculum, dentate gyrus of the hippocampus and the basolateral amygdala. Methylazoxymethanol acetate rats with peripubertal diazepam showed significantly more parvalbumin interneurons (3355±173 in the ventral subiculum, 1211±76 in the dentate gyrus) than methylazoxymethanol acetate without diazepam (2375±109 and 824±54, respectively). No change was found in the basolateral amygdala. Peripubertal diazepam attenuated the decrease of parvalbumin in the ventral hippocampus of methylazoxymethanol acetate rats. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  1. Effects of subchronic benzo(a)pyrene exposure on neurotransmitter receptor gene expression in the rat hippocampus related with spatial learning and memory change.

    Science.gov (United States)

    Qiu, Chongying; Cheng, Shuqun; Xia, Yinyin; Peng, Bin; Tang, Qian; Tu, Baijie

    2011-11-18

    Exposure of laboratory rats to Benzo(a)pyrene (BaP), an environmental contaminant with its high lipophilicify which is widely dispersed in the environment and can easily cross the blood brain barrier presenting in the central nervous system, is associated with impaired learning and memory. The purpose of the research was to examine whether subchronic exposure to BaP affects spatial learning and memory, and how it alters normal gene expression in hippocampus, as well as selection of candidate genes involving neurotransmitter receptor attributed to learning and memory. Morris water maze (MWM) was used to evaluate behavioral differences between BaP-treated and vehicle-treated groups. To gain a better insight into the mechanism of BaP-induced neurotoxicity on learning and memory, we used whole genome oligo microarrays as well as Polymerase Chain Reaction (PCR) to assess the global impact of gene expression. Male Sprague-Dawley rats were intraperitoneally injected with 6.25mg/kg of BaP or vehicle for 14 weeks. The results from the Morris water maze (MWM) test showed that rats treated with BaP exhibited significantly higher mean latencies as compared to vehicle controls. BaP exposure significantly decreased the number of crossing the platform and the time spent in the target area. After the hippocampus was collected from each rat, total RNA was isolated. Microarray and PCR revealed that exposure to BaP affected mRNA expression of neurotransmitter receptors. The web tool DAVID was used to analyze the significantly enriched gene ontology (GO) and KEGG pathways in the differentially expressed genes. Analysis showed that the most significantly affected gene ontology category was behavior. Furthermore, the fourth highest significantly affected gene ontology category was learning and memory. KEGG molecular pathway analysis showed that "neuroactive ligand-receptor interaction" was affected by BaP with highest statistical significance, and 9 candidate neurotransmitter receptor

  2. Mnemonic convergence in the human hippocampus.

    Science.gov (United States)

    Backus, Alexander R; Bosch, Sander E; Ekman, Matthias; Grabovetsky, Alejandro Vicente; Doeller, Christian F

    2016-06-21

    The ability to form associations between a multitude of events is the hallmark of episodic memory. Computational models have espoused the importance of the hippocampus as convergence zone, binding different aspects of an episode into a coherent representation, by integrating information from multiple brain regions. However, evidence for this long-held hypothesis is limited, since previous work has largely focused on representational and network properties of the hippocampus in isolation. Here we identify the hippocampus as mnemonic convergence zone, using a combination of multivariate pattern and graph-theoretical network analyses of functional magnetic resonance imaging data from humans performing an associative memory task. We observe overlap of conjunctive coding and hub-like network attributes in the hippocampus. These results provide evidence for mnemonic convergence in the hippocampus, underlying the integration of distributed information into episodic memory representations.

  3. Selective medial temporal volume reduction in the hippocampus of patients with idiopathic generalized tonic-clonic seizures.

    Science.gov (United States)

    Zhou, Shi-Yu; Tong, Lin; Song, Fan; Hong, Xiao-Jun; Sun, Hui-Fang; Chang, Hong; Xing, Hui-Juan; Li, Zhi-Yong; Dong, Chun-Bo

    2015-02-01

    Different subtypes of idiopathic generalized epilepsy may indicate different mechanisms and outcomes, suggesting that it is necessary to use a 'pure sample' of a single subtype. A volumetric study, in conjunction with cognition assessments, was performed in a pure sample of patients with idiopathic generalized tonic-clonic seizures (IGE-GTCS; 15 males and 15 females) matched with normal control subjects (15 males and 17 females). The volumetric measurements were focused on the hippocampus and its surrounding structures, including the amygdala, the parahippocampal gyrus, the entorhinal cortex and the perirhinal cortex. The Wechsler Adult Intelligence Scale-Revised in China was administered to assess cognitive status. A volume reduction was found only in the hippocampus, with a more severe effect on the left side than the right side. The total number and frequency of seizures had significant negative correlations with multiple cognitive measures. Furthermore, the hippocampal volume reduction was significantly correlated with some aspects of cognitive impairment. These findings suggest that compared with the other medial temporal structures, the hippocampus may be more vulnerable to the neuropathology of IGE-GTCS. The observation that cognitive deterioration was correlated with an increased frequency and total number of seizures highlights the critical importance of preventing seizures from recurrence. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Prevention

    Science.gov (United States)

    ... Tips Latest Research Getting More Help Related Topics Cancer COPD Dementia Depression Diabetes Drug and Substance Abuse Falls Prevention Hearing Loss Heart Attack High Blood Pressure Nutrition Osteoporosis Shingles Skin Cancer Related News Quitting Smoking, ...

  5. Effectiveness and reliability analysis of emergency measures for flood prevention

    NARCIS (Netherlands)

    Lendering, K.T.; Jonkman, S.N.; Kok, M.

    2014-01-01

    During flood events emergency measures are used to prevent breaches in flood defences. However, there is still limited insight in their reliability and effectiveness. The objective of this paper is to develop a method to determine the reliability and effectiveness of emergency measures for flood

  6. Predicting the effect of prevention of ischaemic heart disease

    DEFF Research Database (Denmark)

    Brønnum-Hansen, Henrik

    2002-01-01

    Priority setting in public health policy must be based on information on the effectiveness of alternative preventive and therapeutic interventions. The purpose of this study is to predict the effect on mortality from ischaemic heart disease (IHD) in Denmark of reduced exposure to the risk factors...... hypertension, hypercholesterolaemia, cigarette smoking, and physical inactivity....

  7. 2-Cl-MGV-1 Ameliorates Apoptosis in the Thalamus and Hippocampus and Cognitive Deficits After Cortical Infarct in Rats.

    Science.gov (United States)

    Chen, Yicong; Veenman, Leo; Singh, Sukhdev; Ouyang, Fubing; Liang, Jiahui; Huang, Weixian; Marek, Ilan; Zeng, Jinsheng; Gavish, Moshe

    2017-11-16

    Focal cortical infarction causes neuronal apoptosis in the ipsilateral nonischemic thalamus and hippocampus, which is potentially associated with poststroke cognitive deficits. TSPO (translocator protein) is critical in regulating mitochondrial apoptosis pathways. We examined the effects of the novel TSPO ligand 2-(2-chlorophenyl)quinazolin-4-yl dimethylcarbamate (2-Cl-MGV-1) on poststroke cognitive deficits, neuronal mitochondrial apoptosis, and secondary damage in the ipsilateral thalamus and hippocampus after cortical infarction. One hundred fourteen hypertensive rats underwent successful distal middle cerebral artery occlusion (n=76) or sham procedures (n=38). 2-Cl-MGV-1 or dimethyl sulfoxide as vehicle was administrated 2 hours after distal middle cerebral artery occlusion and then for 6 or 13 days (n=19 per group). Spatial learning and memory were tested using the Morris water maze. Secondary degeneration and mitochondrial apoptosis in the thalamus and hippocampus were assessed using Nissl staining, immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling, JC-1 staining, and immunoblotting 7 and 14 days after surgery. Infarct volumes did not significantly differ between the vehicle and 2-Cl-MGV-1 groups. There were more neurons and fewer glia in the ipsilateral thalamus and hippocampus in the vehicle groups than in the sham-operated group 7 and 14 days post-distal middle cerebral artery occlusion. 2-Cl-MGV-1 significantly ameliorated spatial cognitive impairment and decreased neuronal death and glial activation when compared with vehicle treatment (P<0.05). The collapse of mitochondrial transmembrane potential and cytoplasmic release of apoptosis-inducing factors and cytochrome c was prevented within the thalamus. Caspase cleavage and the numbers of terminal deoxynucleotidyl transferase dUTP nick end labeling(+) or Nissl atrophic cells were reduced within the thalamus and hippocampus. This was accompanied by upregulation of B

  8. Chronic lithium treatment has antioxidant properties but does not prevent oxidative damage induced by chronic variate stress.

    Science.gov (United States)

    de Vasconcellos, Ana Paula Santana; Nieto, Fabiane Battistela; Crema, Leonardo Machado; Diehl, Luisa Amália; de Almeida, Lúcia Maria; Prediger, Martha Elisa; da Rocha, Elizabete Rocha; Dalmaz, Carla

    2006-09-01

    This study evaluated the effects of chronic stress and lithium treatments on oxidative stress parameters in hippocampus, hypothalamus, and frontal cortex. Adult male Wistar rats were divided into two groups: control and submitted to chronic variate stress, and subdivided into treated or not with LiCl. After 40 days, rats were killed, and lipoperoxidation, production free radicals, total antioxidant reactivity (TAR) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were evaluated. The results showed that stress increased lipoperoxidation and that lithium decreased free radicals production in hippocampus; both treatments increased TAR. In hypothalamus, lithium increased TAR and no effect was observed in the frontal cortex. Stress increased SOD activity in hippocampus; while lithium increased GPx in hippocampus and SOD in hypothalamus. We concluded that lithium presented antioxidant properties, but is not able to prevent oxidative damage induced by chronic variate stress.

  9. Fornix deep brain stimulation enhances acetylcholine levels in the hippocampus.

    Science.gov (United States)

    Hescham, Sarah; Jahanshahi, Ali; Schweimer, Judith V; Mitchell, Stephen N; Carter, Guy; Blokland, Arjan; Sharp, Trevor; Temel, Yasin

    2016-11-01

    Deep brain stimulation (DBS) of the fornix has gained interest as a potential therapy for advanced treatment-resistant dementia, yet the mechanism of action remains widely unknown. Previously, we have reported beneficial memory effects of fornix DBS in a scopolamine-induced rat model of dementia, which is dependent on various brain structures including hippocampus. To elucidate mechanisms of action of fornix DBS with regard to memory restoration, we performed c-Fos immunohistochemistry in the hippocampus. We found that fornix DBS induced a selective activation of cells in the CA1 and CA3 subfields of the dorsal hippocampus. In addition, hippocampal neurotransmitter levels were measured using microdialysis before, during and after 60 min of fornix DBS in a next experiment. We observed a substantial increase in the levels of extracellular hippocampal acetylcholine, which peaked 20 min after stimulus onset. Interestingly, hippocampal glutamate levels did not change compared to baseline. Therefore, our findings provide first experimental evidence that fornix DBS activates the hippocampus and induces the release of acetylcholine in this region.

  10. Aberrant NMDA-dependent LTD after perinatal ethanol exposure in young adult rat hippocampus.

    Science.gov (United States)

    Kervern, Myriam; Silvestre de Ferron, Benoît; Alaux-Cantin, Stéphanie; Fedorenko, Olena; Antol, Johann; Naassila, Mickael; Pierrefiche, Olivier

    2015-08-01

    Irreversible cognitive deficits induced by ethanol exposure during fetal life have been ascribed to a lower NMDA-dependent synaptic long-term potentiation (LTP) in the hippocampus. Whether NMDA-dependent long-term depression (LTD) may also play a critical role in those deficits remains unknown. Here, we show that in vitro LTD induced with paired-pulse low frequency stimulation is enhanced in CA1 hippocampus field of young adult rats exposed to ethanol during brain development. Furthermore, single pulse low frequency stimulation, ineffective at this age (LFS600), induced LTD after ethanol exposure accompanied with a stronger response than controls during LFS600, thus revealing an aberrant form of activity-dependent plasticity at this age. Blocking NMDA receptor or GluN2B containing NMDA receptor prevented both the stronger response during LFS600 and LTD whereas Zinc, an antagonist of GluN2A containing NMDA receptor, was ineffective on both responses. In addition, LFS600-induced LTD was revealed in controls only with a reduced-Mg(2+) medium. In whole dissected hippocampus CA1 field, perinatal ethanol exposure increased GluN2B subunit expression in the synaptic compartment whereas GluN2A was unaltered. Using pharmacological tools, we suggest that LFS600 LTD was of synaptic origin. Altogether, we describe a new mechanism by which ethanol exposure during fetal life induces a long-term alteration of synaptic plasticity involving NMDA receptors, leading to an aberrant LTD. We suggest this effect of ethanol may reflect a delayed maturation of the synapse and that aberrant LTD may also participates to long-lasting cognitive deficits in fetal alcohol spectrum disorder. © 2015 Wiley Periodicals, Inc.

  11. Effectiveness of anterior cruciate ligament injury prevention training programs.

    Science.gov (United States)

    Sadoghi, Patrick; von Keudell, Arvind; Vavken, Patrick

    2012-05-02

    The objective of this study was to systematically review the literature on anterior cruciate ligament (ACL) injury prevention programs and to perform a meta-analysis to address three questions: First, what is the effectiveness of ACL injury prevention programs? Second, is there evidence for a "best" program? Third, what is the quality of the current literature on ACL injury prevention? We conducted a systematic review with use of the online PubMed, MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health), and Cochrane Central Register of Controlled Trials databases. Search terms were anterior cruciate ligament, knee, injury, prevention, and control. Data on study design and clinical outcomes were extracted independently in triplicate. After assessment of between-study heterogeneity, DerSimonian-Laird random-effect models were used to calculate pooled risk ratios and risk differences. The risk difference was used to estimate the number needed to treat (the number of individuals who would need to be treated to avoid one ACL tear). The pooled risk ratio was 0.38 (95% confidence interval [CI], 0.20 to 0.72), reflecting a significant reduction in the risk of ACL rupture in the prevention group (p = 0.003). The number needed to treat ranged from five to 187 in the individual studies. Stratified by sex, the pooled risk ratio was 0.48 (95% CI, 0.26 to 0.89) for female athletes and 0.15 (95% CI, 0.08 to 0.28) for male athletes. Our study indicated strong evidence in support of a significant effect of ACL injury prevention programs. Our pooled estimates suggest a substantial beneficial effect of ACL injury prevention programs, with a risk reduction of 52% in the female athletes and 85% in the male athletes.

  12. Resistance exercise improves hippocampus-dependent memory

    Directory of Open Access Journals (Sweden)

    R.C. Cassilhas

    2012-12-01

    Full Text Available It has been demonstrated that resistance exercise improves cognitive functions in humans. Thus, an animal model that mimics this phenomenon can be an important tool for studying the underlying neurophysiological mechanisms. Here, we tested if an animal model for resistance exercise was able to improve the performance in a hippocampus-dependent memory task. In addition, we also evaluated the level of insulin-like growth factor 1/insulin growth factor receptor (IGF-1/IGF-1R, which plays pleiotropic roles in the nervous system. Adult male Wistar rats were divided into three groups (N = 10 for each group: control, SHAM, and resistance exercise (RES. The RES group was submitted to 8 weeks of progressive resistance exercise in a vertical ladder apparatus, while the SHAM group was left in the same apparatus without exercising. Analysis of a cross-sectional area of the flexor digitorum longus muscle indicated that this training period was sufficient to cause muscle fiber hypertrophy. In a step-through passive avoidance task (PA, the RES group presented a longer latency than the other groups on the test day. We also observed an increase of 43 and 94% for systemic and hippocampal IGF-1 concentration, respectively, in the RES group compared to the others. A positive correlation was established between PA performance and systemic IGF-1 (r = 0.46, P < 0.05. Taken together, our data indicate that resistance exercise improves the hippocampus-dependent memory task with a concomitant increase of IGF-1 level in the rat model. This model can be further explored to better understand the effects of resistance exercise on brain functions.

  13. Caffeine and modafinil given during 48 h sleep deprivation modulate object recognition memory and synaptic proteins in the hippocampus of the rat.

    Science.gov (United States)

    Wadhwa, M; Sahu, S; Kumari, P; Kauser, H; Ray, K; Panjwani, U

    2015-11-01

    We aimed to evaluate the effect of caffeine/modafinil on sleep deprivation (SD) induced alterations in recognition memory and synaptic proteins. The data revealed a beneficial effect of caffeine/modafinil against deficit in the familiar object retrieval performance and object exploration ratio after 48 h SD. Caffeine treatment prevented the SD induced down-regulation of synaptophysin and synapsin I proteins with no change in PSD-95 protein in hippocampus. However, modafinil administration improved the down-regulation of synaptophysin, synapsin I and PSD-95 proteins in hippocampus. Hence, caffeine/modafinil can serve as counter measures in amelioration of SD induced consequences at behavioural and protein levels. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Obesity in aging exacerbates blood-brain barrier disruption, neuroinflammation, and oxidative stress in the mouse hippocampus: effects on expression of genes involved in beta-amyloid generation and Alzheimer's disease.

    Science.gov (United States)

    Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Mitschelen, Matthew; Koller, Akos; Szalai, Gabor; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2014-10-01

    There is growing evidence that obesity has deleterious effects on the brain and cognitive function in the elderly population. However, the specific mechanisms through which aging and obesity interact to promote cognitive decline remain unclear. To test the hypothesis that aging exacerbates obesity-induced cerebromicrovascular damage and neuroinflammation, we compared young (7 months) and aged (24 months) high fat diet-fed obese C57BL/6 mice. Aging exacerbated obesity-induced systemic inflammation and blood-brain barrier disruption, as indicated by the increased circulating levels of proinflammatory cytokines and increased presence of extravasated immunoglobulin G in the hippocampus, respectively. Obesity-induced blood-brain barrier damage was associated with microglia activation, upregulation of activating Fc-gamma receptors and proinflammatory cytokines, and increased oxidative stress. Treatment of cultured primary microglia with sera derived from aged obese mice resulted in significantly more pronounced microglia activation and oxidative stress, as compared with treatment with young sera. Serum-induced activation and oxidative stress were also exacerbated in primary microglia derived from aged animals. Hippocampal expression of genes involved in regulation of the cellular amyloid precursor protein-dependent signaling pathways, beta-amyloid generation, and the pathogenesis of tauopathy were largely unaffected by obesity in aged mice. Collectively, obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates blood-brain barrier disruption. The resulting neuroinflammation and oxidative stress in the mouse hippocampus likely contribute to the significant cognitive decline observed in aged obese animals. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Effects of Aluminium on Long-Term Memory in Rats and on SIRT1 Mediating the Transcription of CREB-Dependent Gene in Hippocampus.

    Science.gov (United States)

    Yan, Dongying; Jin, Cuihong; Cao, Yang; Wang, Lulu; Lu, Xiaobo; Yang, Jinghua; Wu, Shengwen; Cai, Yuan

    2017-10-01

    Epidemiological investigations have shown that aluminium (Al) is an important neurotoxicant which can be absorbed by organisms via various routes. Previous studies have confirmed that exposure to Al could cause neurodegenerative diseases, decline CREB phosphorylation and then down-regulate the transcription and protein expression of its target genes including BDNF. However, recent studies revealed that CREB activation alone was far from enough to activate the expression of long-term memory (LTM)-related genes; there might be other regulatory factors involved in this process. Several studies showed that TORC1 might be involved in regulating the transcription of downstream target genes as well. Also, TORC1 could be mediated by SIRT1 during the formation of LTM. However, the role of CREB regulating system in Al-induced LTM impairment was still not utterly elucidated till now. This study was designed to establish the rat model of subchronic Al exposure to observe the neuroethology, regulatory factor levels and molecular biological alterations in hippocampal cells. The results showed that, with the increasing AlCl3 dose, blood Al content increased gradually; morphology of the hippocampus and neuronal ultrastructure were aberrant; in the Morris water maze test, the escape latency and distance travelled became longer, swimming traces turned more complicated in the place navigation test; intracellular Ca2+ , cAMP levels declined significantly in AlCl3 -treated rats, followed by abated nuclear translocation of TORC1 and decreased SIRT1, TORC1 and pCREB levels. These results indicate that SIRT1 and TORC1 might play an important mediating role in Al-induced LTM impairment. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  16. Cortical representations are reinstated by the hippocampus during memory retrieval.

    Science.gov (United States)

    Tanaka, Kazumasa Z; Pevzner, Aleksandr; Hamidi, Anahita B; Nakazawa, Yuki; Graham, Jalina; Wiltgen, Brian J

    2014-10-22

    The hippocampus is assumed to retrieve memory by reinstating patterns of cortical activity that were observed during learning. To test this idea, we monitored the activity of individual cortical neurons while simultaneously inactivating the hippocampus. Neurons that were active during context fear conditioning were tagged with the long-lasting fluorescent protein H2B-GFP and the light-activated proton pump ArchT. These proteins allowed us to identify encoding neurons several days after learning and silence them with laser stimulation. When tagged CA1 cells were silenced, we found that memory retrieval was impaired and representations in the cortex (entorhinal, retrosplenial, perirhinal) and the amygdala could not be reactivated. Importantly, hippocampal inactivation did not alter the total amount of activity in most brain regions. Instead, it selectively prevented neurons that were active during learning from being reactivated during retrieval. These data provide functional evidence that the hippocampus reactivates specific memory representations during retrieval. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Preventive Effects of Cocoa and Cocoa Antioxidants in Colon Cancer

    Directory of Open Access Journals (Sweden)

    María Angeles Martín

    2016-01-01

    Full Text Available Colorectal cancer is one of the main causes of cancer-related mortality in the developed world. Carcinogenesis is a multistage process conventionally defined by the initiation, promotion and progression stages. Natural polyphenolic compounds can act as highly effective antioxidant and chemo-preventive agents able to interfere at the three stages of cancer. Cocoa has been demonstrated to counteract oxidative stress and to have a potential capacity to interact with multiple carcinogenic pathways involved in inflammation, proliferation and apoptosis of initiated and malignant cells. Therefore, restriction of oxidative stress and/or prevention or delayed progression of cancer stages by cocoa antioxidant compounds has gained interest as an effective approach in colorectal cancer prevention. In this review, we look over different in vitro and in vivo studies that have identified potential targets and mechanisms whereby cocoa and their flavonoids could interfere with colonic cancer. In addition, evidence from human studies is also illustrated.

  18. Prevention

    Science.gov (United States)

    ... Protection Equipment (PPE) Sequence for Putting on Personal Protection Equipment (PPE) [PDF – 2.85MB] Select Your PPE Equipment Combination Guidance ... PDF, DOC, PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word ... last updated: May 11, 2015 Content Source: Centers for Disease Control and Prevention National Center ...

  19. The tired hippocampus : The molecular impact of sleep deprivation on hippocampal function

    NARCIS (Netherlands)

    Havekes, Robbert; Abel, Ted

    2017-01-01

    Memory consolidation, the process by which information is stored following training, consists of synaptic consolidation and systems consolidation. It is widely acknowledged that sleep deprivation has a profound effect on synaptic consolidation, particularly for memories that require the hippocampus.

  20. Transient inactivation of the neonatal ventral hippocampus impairs attentional set-shifting behavior

    DEFF Research Database (Denmark)

    Brooks, Julie M; Pershing, Michelle L; Thomsen, Morten Skøtt

    2012-01-01

    Cognitive deficits represent a core symptom cluster in schizophrenia that are thought to reflect developmental dysregulations within a neural system involving the ventral hippocampus (VH), nucleus accumbens (NAC), and prefrontal cortex (PFC). The present experiments determined the cognitive effects...

  1. Effect of intermittent preventive treatment of malaria on the outcome ...

    African Journals Online (AJOL)

    Objective: The study was on the effect of intermittent preventive treatment of malaria in pregnancy on the prevalence of malaria in pregnancy and the outcome of pregnancy. Method: It was a prospective descriptive cross-sectional study and a semi-structured questionnaire was administered to women in the lying in ward ...

  2. Effect of health education on knowledge and prevention on Hepatitis ...

    African Journals Online (AJOL)

    The study examined the effect of health education on knowledge and prevention of hepatitis infection among senior secondary school students in Ibadan North Local Government Area of Oyo State. The research design was pretest, post test, control group, quasi-experimental design. A total of 180 students were selected ...

  3. REBAMIPIDE: EFFECTIVE DRUG PREVENTION OF NSAID ENTEROPATHY IS POSSIBLE

    Directory of Open Access Journals (Sweden)

    E. V. Moroz

    2016-01-01

    Full Text Available Prevention of gastrointestinal tract (GIT complications is the most important element for the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs and low-dose aspirin (LDA. Proton pump inhibitors (PPIs have long been the only medication to prevent these complications. However, PPIs are only effective in preventing and treating upper GIT diseases (NSAID gastropathy rather than small intestinal injury (NSAID enteropathy. Rebamipide has emerged as a novel agent to protect the gastrointestinal mucosa today. The effect of the drug differs from that of PPIs: it is a typical gastroand enteroprotector that enhances the synthesis of endogenous prostaglandins and possesses a significant anti-inflammatory potential. Rebamipide has long been widely used by doctors inJapan,South Korea, andChinaas an effective and safe agent for the treatment of many diseases of the digestive system. There is a strong evidence base for the efficacy of rebamipide in preventing and treating NSAID gastropathy and NSAID enteropathy (including LDA-induced injuries. Controlled studies have found that the drug is not inferior to the classic gastroprotective agent misoprostol, significantly outperforming the latter in its tolerability. This review describes the mechanism of action of rebamipide and main clinical trials of its therapeutic effect in NSAID gastropathy and NSAID enteropathy. 

  4. Caries-preventive Effect of Supervised Toothbrushing and Sealants

    NARCIS (Netherlands)

    Hilgert, L.A.; Leal, S.C.; Mulder, J.; Creugers, N.H.J.; Frencken, J.E.F.M.

    2015-01-01

    To investigate the effectiveness of 3 caries-preventive measures on high- and low-caries risk occlusal surfaces of first permanent molars over 3 y. This cluster-randomized controlled clinical trial covered 242 schoolchildren, 6 to 7 y old, from low socioeconomic areas. At baseline, caries risk was

  5. Fetal Alcohol Spectrum Disorders (FASD): an Approach to Effective Prevention

    NARCIS (Netherlands)

    Roozen, Sylvia; Black, Diane; Peters, Gjalt-Jorn; Kok, Gerjo; Townend, David; Nijhuis, Jan; Koek, Ger; Curfs, Leopold

    2016-01-01

    Purpose of Review The objective of the current contribution is to propose an evidence-based, six-step approach to develop effective programs for prevention of fetal alcohol spectrum disorders. Recent Findings Despite widespread campaigns aimed to reduce prenatal alcohol exposure, the number of

  6. Effect of intermittent preventive treatment of malaria on the outcome ...

    African Journals Online (AJOL)

    Saharan Africa and among the under five children and pregnant women and is associated with a lot of maternal and foetal complications. Objective: The study was on the effect of intermittent preventive treatment of malaria in pregnancy on the ...

  7. Household Barriers to Effective Malaria Prevention and Control in a ...

    African Journals Online (AJOL)

    Background: Malaria is endemic throughout Nigeria. Majority of Nigerians live in rural areas where subsistence farming is their main occupation. Most of them live below poverty line, earning less than $1.25 a day. In rural communities, many household factors constitute barriers to effective malaria prevention and control.

  8. How Effective Homelessness Prevention Impacts the Length of Shelter Spells.

    Science.gov (United States)

    Goodman, Sarena; Messeri, Peter; O'Flaherty, Brendan

    2014-03-01

    Homelessness prevention programs intervene with households apparently in imminent danger of becoming homeless, and try to keep them housed. If they are at least partially successful, how do they change the average shelter spell of households actually becoming homeless? We use data from 2003 to 2008 for Homebase, a New York City homelessness prevention program that studies have found to be effective in reducing shelter entries. Homebase made no difference in average shelter spells at the community level. This result, like many results about shelter spell length, is not easy to reconcile with the idea that shelter spell length is a reflection of the seriousness of underlying problems.

  9. Effectiveness and Evaluation of Crime Prevention Programs in Minas Gerais

    Directory of Open Access Journals (Sweden)

    Claudio Beato

    2014-05-01

    Full Text Available This essay analyzes previous studies evaluating the effectiveness of the crime prevention policies adopted by the Government of Minas Gerais (Brazil. In this work, greater emphasis is placed on studies evaluating outcomes than on studies dealing with the process of setting up and implementing programs and projects. In order to allow a more systematic discussion, the Maryland Scale, which categorizes research and evaluations according to the methodological strengths and weaknesses in five levels, is employed. Subsequently, the authors draw a parallel between Brazil and other settings. Finally, this essay lays out the implications of this discussion regarding the prevention programs. 

  10. The modifying effect of diabetes mellitus on the reaction of р53-dependent proapoptotic mechanisms of hippocampus of rats in dynamic of ischemic-reperfusion damage of brain

    Directory of Open Access Journals (Sweden)

    T. M. Boychuk

    2016-12-01

    Full Text Available A few studies are devoted to mechanisms of death of hippocampal cells under conditions of complications of diabetes mellitus (DM with acute disorders of cerebral circulation, although the frequency of ischemic-reperfusion brain damage on a background of diabetes is much higher than that in the general population. The objective of research is to study the state of p53-dependent proapoptotic mechanisms in the hippocampal fields in the dynamic of ischemic-reperfusion brain damage in rats with experimental diabetes mellitus. Materials and methods. In neurons of hippocampal fields of rats with experimental DM content of p53 protein was studied by immunofluorescence using monoclonal antibodies in dynamic of incomplete global brain ischemia-reperfusion. The diabetes mellitus was modeled by single intraperitoneal injection of streptozotocin (Sigma, USA, 60 mg / kg. The results were estimated after a 20-minute carotic ischemia combined with one-hour reperfusion and on the 12th day of postischemic period. Results. After 20 minutes of ischemia / one hour reperfusion, in rats without DM and with DM, the activity of p53 proapoptotic processes increased in all the fields of hippocampus, only in the last group of rats its indices significantly exceed these are in hippocampal fields CA1, CA3, CA4 of rats without diabetes. On the 12th day of postischemic period in hippocampal fields CA1-CA3 of rats without diabetes the proapoptotic activity remains high, and in the field CA4 returns to normal level. In this period, in rats with diabetes activity of p53 proapoptotic processes remains increased in the field of CA1, returns to the level in rats with diabetes in the field of CA2, and decreases – in the fields CA3 and СA4. Conclusions. Diabetes mellitus quantitatively modifies the reaction of product of proapoptotic gene of p53 protein to the ischemic-reperfusion injury of the brain in the early postischemic period in the hippocampal fields CA1-CA3 and

  11. Age-Related Modulations of AQP4 and Caveolin-1 in the Hippocampus Predispose the Toxic Effect of Phoneutria nigriventer Spider Venom

    Directory of Open Access Journals (Sweden)

    Edilene S. Soares

    2016-11-01

    Full Text Available We have previously demonstrated that Phoneutria nigriventer venom (PNV causes blood–brain barrier (BBB breakdown, swelling of astrocytes end-feet and fluid permeation into brain interstitium in rats. Caveolae and water channels respond to BBB alterations by co-participation in shear stress response and edema formation/resolution. Herein, we showed post-natal developmental-related changes of two BBB-associated transporter proteins: the endothelial caveolin-1 (Cav-1, the major scaffolding protein from caveolae frame, and the astroglial aquaporin-4 (AQP4, the main water channel protein expressed in astrocytic peri-vascular end-feet processes, in the hippocampus of rats intraperitoneally-administered PNV. Western blotting protein levels; immunohistochemistry (IHC protein distribution in CA1, CA2, and CA3 subfields; and gene expression by Real Time-Polymerase Chain Reaction (qPCR were assessed in post-natal Day 14 (P14 and 8–10-week-old rats over critical periods of envenomation. The intensity and duration of the toxic manifestations indicate P14 neonate rats more vulnerable to PNV than adults. Histologically, the capillaries of P14 and 8–10-week-old rats treated with PNV showed perivascular edema, while controls did not. The intensity of the toxic manifestations in P14 decreases temporally (2 > 5 > 24 h, while inversely the expression of AQP4 and Cav-1 peaked at 24 h when clinically PNV-treated animals do not differ from saline controls. IHC of AQP4 revealed that hippocampal CA1 showed the least expression at 2 h when toxic manifestation was maximal. Subfield IHC quantification revealed that in P14 rats Cav-1 peaked at 24 h when toxic manifestations were absent, whereas in 8–10-week-old rats Cav-1 peaked at 2 h when toxic signs were highest, and progressively attenuated such increases until 24 h, remaining though significantly above baseline. Considering astrocyte-endothelial physical and functional interactions, we hypothesize that age

  12. The beneficial effects of taurine in preventing metabolic syndrome.

    Science.gov (United States)

    Chen, Wen; Guo, Junxia; Zhang, Yanzhen; Zhang, Jing

    2016-04-01

    Metabolic syndrome, a cluster of risk factors for diabetes and cardiovascular disease, has become a very serious public health concern. A number of studies have provided evidence that taurine has an efficient action against metabolic syndrome, which includes reducing triglycerides to prevent obesity, improving insulin resistance to regulate glucose metabolism, lowering cholesterol (especially decreasing VLDL + LDL cholesterol and increasing HDL cholesterol) to prevent diet-induced hypercholesterolemia, and regulating the renin-angiotensin-aldosterone system and the kallikrein-kinin system etc. to reduce blood pressure. This review summarizes the data from in vitro, animal and limited human studies of beneficial effects of taurine on obesity, dyslipidaemia, diabetes mellitus and hypertension, and addresses the possible metabolic and molecular mechanisms of the prevention of metabolic syndrome by taurine.

  13. Parenting through change: an effective prevention program for single mothers.

    Science.gov (United States)

    Forgatch, M S; DeGarmo, D S

    1999-10-01

    This randomized experimental prevention study (a) evaluated the effectiveness of a parent-training program in a sample of 238 divorcing mothers with sons in Grades 1-3 and (b) provided an experimental test of coercion theory. The intervention produced reductions in observed coercive parenting, prevented decay in positive parenting, and generally improved effective parenting practices in comparisons of mothers in experimental and control groups. Moreover, coercion theory was supported. Improved parenting practices correlated significantly with improvements in teacher-reported school adjustment, child-reported maladjustment, and mother-reported maladjustment. The intervention indirectly benefitted child outcomes through improved parenting practices for a model based on child report and, to a lesser extent, on teacher report. The intervention did not produce direct effects on child outcomes.

  14. Preventive effects of Flos Perariae (Gehua water extract and its active ingredient puerarin in rodent alcoholism models

    Directory of Open Access Journals (Sweden)

    Wang Yuqiang

    2010-10-01

    Full Text Available Abstract Background Radix Puerariae is used in Chinese medicine to treat alcohol addiction and intoxication. The present study investigates the effects of Flos puerariae lobatae water extract (FPE and its active ingredient puerarin on alcoholism using rodent models. Methods Alcoholic animals were given FPE or puerarin by oral intubation prior or after alcohol treatment. The loss of righting reflex (LORR assay was used to evaluate sedative/hypnotic effects. Changes of gama-aminobutyric acid type A receptor (GABAAR subunits induced by alcohol treatment in hippocampus were measured with western blot. In alcoholic mice, body weight gain was monitored throughout the experiments. Alcohol dehydrogenase (ADH levels in liver were measured. Results FPE and puerarin pretreatment significantly prolonged the time of LORR induced by diazepam in acute alcoholic rat. Puerarin increased expression of gama-aminobutyric acid type A receptor alpha1 subunit and decreased expression of alpha4 subunit. In chronic alcoholic mice, puerarin pretreatment significantly increased body weight and liver ADH activity in a dose-dependent manner. Puerarin pretreatment, but not post-treatment, can reverse the changes of gama-aminobutyric acid type A receptor subunit expression and increase ADH activity in alcoholism models. Conclusion The present study demonstrates that FPE and its active ingredient puerarin have preventive effects on alcoholism related disorders.

  15. Effect of Yi-nao-jie-yu decoction on γ-aminobutyric acid type A receptor in the hippocampus and serum inflammatory factors in a rat model of poststroke anxiety

    Directory of Open Access Journals (Sweden)

    Zhang W

    2016-11-01

    Full Text Available Wen Zhang,1 Ruizhen Zhao,1 Xiaoli Li,1 Xia Cui,1 Zijun Zhao,1 Yingqiu Mao,2 Fengzhi Wu,3 Qisheng Tang1 1Department of Encephalopathy, The Third Affiliated Hospital, 2Center of Scientific Research, 3Center of Journals, Beijing University of Chinese Medicine, Chaoyang District, Beijing, People’s Republic of China Background: The Yi-nao-jie-yu decoction (YNJYD is a herbal preparation widely used in the clinics of traditional Chinese medicine and has been recently used as an important new therapeutic agent in poststroke anxiety (PSA. The neuroendocrine–immune system plays an important role in PSA mechanisms, although the modulating effects of YNJYD remain unknown. This study investigated the potential effects of YNJYD on the neuroendocrine–immune system in a rat model of PSA.Materials and methods: The PSA model was induced by injecting collagenase (type VII into the right globus pallidus, accompanied by empty water bottle stimulation for 2 weeks. The sham group and the PSA model group were gavaged with saline, while the treatment groups received buspirone (BuSpar or YNJYD. Behavior was evaluated with the open field test and elevated plus maze once a week. Pathological changes were observed by hematoxylin and eosin staining. Serum levels of tumor necrosis factor, interleukin (IL-6, adrenocorticotropic hormone, thyroid stimulating hormone, free triiodothyronine, free thyroxine, IL-1α, and cortisol were detected by radioimmunoassay. Expression of the γ-aminobutyric acid type A receptor (GABAAR α2 subunit was examined by Western blot and real-time polymerase chain reaction.Results: YNJYD-treated rats exhibited significantly better recovery than BuSpar-treated rats at 21 days and 28 days in the open field test and elevated plus maze. Hematoxylin and eosin staining revealed neural repair in the hippocampus in the treatment groups. Serum levels of IL-1α in the YNJYD group were significantly less than those in the model group and the Bu

  16. Adeno-Associated Viral Vector-Induced Overexpression of Neuropeptide Y Y2 Receptors in the Hippocampus Suppresses Seizures

    Science.gov (United States)

    Woldbye, David P. D.; Angehagen, Mikael; Gotzsche, Casper R.; Elbrond-Bek, Heidi; Sorensen, Andreas T.; Christiansen, Soren H.; Olesen, Mikkel V.; Nikitidou, Litsa; Hansen, Thomas v. O.; Kanter-Schlifke, Irene; Kokaia, Merab

    2010-01-01

    Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure suppression by neuropeptide Y in the hippocampus is…

  17. Antioxidant activity of Citrus limon essential oil in mouse hippocampus.

    Science.gov (United States)

    Campêlo, Lidianne Mayra Lopes; Gonçalves, Fabrício Custódio Moura; Feitosa, Chistiane Mendes; de Freitas, Rivelilson Mendes

    2011-07-01

    Citrus limon (L.) Burms (Rutaceae) has been shown in previous studies to have various biological functions (anti-inflammatory, antiallergic, antiviral, antimutagenic, and anticarcinogenic). However, traditional uses in folk medicine suggest that C. limon may have an effect on the central nervous system (CNS). This study investigated the effects of C. limon essential oil (EO) on lipid peroxidation level, nitrite content, glutathione reduced (GSH) concentration, and antioxidant enzymes [superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx)] activities in mice hippocampus. Swiss mice were treated with the suspension of 0.5% Tween 80, in distilled water used as vehicle (i.p., control group) and with EO in three different doses (0.05, 0.1, or 0.15 g/kg, i.p., EO 50, EO 100, and EO 150 groups, respectively). After the treatments, all groups were observed for 24 h. The enzyme activities as well as the lipid peroxidation, nitrite, and GSH concentrations in mice hippocampus were measured using spectrophotometric methods and the results were compared with values obtained from control group. EO of C. limon treatment significantly reduced the lipid peroxidation level and nitrite content but increased the GSH levels and the SOD, catalase, and GPx activities in mice hippocampus. Our findings strongly support the hypothesis that oxidative stress in hippocampus can occur during neurodegenerative diseases, proving that hippocampal damage induced by the oxidative process plays a crucial role in brain disorders, and also imply that a strong protective effect could be achieved using EO of C. limon as an antioxidant.

  18. Preventive effects of physical exercise on the inhibition of creatine kinase in the cerebral cortex of mice exposed to cigarette smoke. DOI: 10.5007/1980-0037.2011v13n2p106

    Directory of Open Access Journals (Sweden)

    Daiane Bittencourt Fraga

    2011-02-01

    Full Text Available Recent studies have shown the health benefits of physical exercise, increasing the oxidative response of muscle. However, the effects of exercise on the brain are poorly understood and contradictory. The inhibition of creatine kinase (CK activity has been associated with the pathogenesis of a large number of diseases, especially in the brain. The objective of this study was to determine the preventive effects of physical exercise in the hippocampus and cerebral cortex of mice after chronic cigarette smoke exposure. Eight to 10-week-old male mice (C57BL-6 were divided into four groups and submitted to an exercise program (swimming, 5 times a week, for 8 weeks. After this period, the animals were passively exposed to cigarette smoke for 60 consecutive days, 3 times a day (4 Marlboro red cigarettes per session, for a total of 12 cigarettes. CK activity was measured in cerebral cortex and hippocampal homogenates. Enzyme activity was inhibited in the cerebral cortex of animals submitted to the inhalation of cigarette smoke. However, exercise prevented this inhibition. In contrast, CK activity remained unchanged in the hippocampus. This inhibition of CK by inhalation of cigarette smoke might be related to the process of cell death. Physical exercise played a preventive role in the inhibition of CK activity caused by exposure to cigarette smoke.

  19. Preventive effects of physical exercise on the inhibition of creatine kinase in the cerebral cortex of mice exposed to cigarette smoke. DOI: 10.5007/1980-0037.2011v13n2p106

    Directory of Open Access Journals (Sweden)

    Daiane Bittencourt Fraga

    2011-03-01

    Full Text Available Recent studies have shown the health benefits of physical exercise, increasing the oxidative response of muscle. However, the effects of exercise on the brain are poorly understood and contradictory. The inhibition of creatine kinase (CK activity has been associated with the pathogenesis of a large number of diseases, especially in the brain. The objective of this study was to determine the preventive effects of physical exercise in the hippocampus and cerebral cortex of mice after chronic cigarette smoke exposure. Eight to 10-week-old male mice (C57BL-6 were divided into four groups and submitted to an exercise program (swimming, 5 times a week, for 8 weeks. After this period, the animals were passively exposed to cigarette smoke for 60 consecutive days, 3 times a day (4 Marlboro red cigarettes per session, for a total of 12 cigarettes. CK activity was measured in cerebral cortex and hippocampal homogenates. Enzyme activity was inhibited in the cerebral cortex of animals submitted to the inhalation of cigarette smoke. However, exercise prevented this inhibition. In contrast, CK activity remained unchanged in the hippocampus. This inhibition of CK by inhalation of cigarette smoke might be related to the process of cell death. Physical exercise played a preventive role in the inhibition of CK activity caused by exposure to cigarette smoke.

  20. The moderating effects of school climate on bullying prevention efforts.

    Science.gov (United States)

    Low, Sabina; Van Ryzin, Mark

    2014-09-01

    Bullying prevention efforts have yielded mixed effects over the last 20 years. Program effectiveness is driven by a number of factors (e.g., program elements and implementation), but there remains a dearth of understanding regarding the role of school climate on the impact of bullying prevention programs. This gap is surprising, given research suggesting that bullying problems and climate are strongly related. The current study examines the moderating role of school climate on the impacts of a stand-alone bullying prevention curriculum. In addition, the current study examined 2 different dimensions of school climate across both student and staff perceptions. Data for this study were derived from a Steps to Respect (STR) randomized efficacy trial that was conducted in 33 elementary schools over a 1-year period. Schools were randomly assigned to intervention or wait-listed control condition. Outcome measures (pre-to-post) were obtained from (a) all school staff, (b) a randomly selected subset of 3rd-5th grade teachers in each school, and (c) all students in classrooms of selected teachers. Multilevel analyses revealed that psychosocial climate was strongly related to reductions in bullying-related attitudes and behaviors. Intervention status yielded only 1 significant main effect, although, STR schools with positive psychosocial climate at baseline had less victimization at posttest. Policies/administrative commitment to bullying were related to reduced perpetration among all schools. Findings suggest positive psychosocial climate (from both staff and student perspective) plays a foundational role in bullying prevention, and can optimize effects of stand-alone programs. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  1. Evaluation of antioxidant activities in captive-bred cultured yellow seahorse, Hippocampus kuda (Bleeker, 1852).

    Digital Repository Service at National Institute of Oceanography (India)

    Sanaye, S.V.; Pise, N.M.; Pawar, A.P.; Parab, P.P.; Sreepada, R.A.; Pawar, H.B.; Revankar, A.D.

    Aquaculture Laboratory, National Institute of Oceanography (NIO), Council of Scientific & Industrial Research (CSIR), Dona Paula, Goa─403 004 (India) __________________________________________________________________________ Abstract Globally, seahorses... (Chinese and Taiwanese) with incomplete methodology thus preventing the wider application of the obtained results. The yellow seahorse, Hippocampus kuda (Bleeker, 1852) is one of the heavily traded in many Southeast Asian countries mostly for TCM (Job et...

  2. Preventive and curative effects of probiotics in atopic patients.

    Science.gov (United States)

    Bongaerts, G P A; Severijnen, R S V M

    2005-01-01

    Normally, the transport of allergens through the intestinal epithelia to the blood is limited. It is hypothesised that if these compounds arrive in the blood circulation, they must percolate through the epithelial cell layer. Thus, food allergy (and thus atopic eczema) implies an increased intercellular leakage of the gut wall. Such increased intercellular leakage is thought to be caused by a slightly changed cellular morphology due to a slight cytopathologic effect because of both a limited decay of the cytoskeleton and a slightly reduced turgor. These events may be due to a reduced production of intracellular metabolic energy in the epithelial cells due to an increased concentration of familiar, frequently occurring, potentially toxic bacterial metabolites, i.e., d-lactic acid and/or ethanol. In this hypothesis we suggest that adequate probiotics can (i) prevent the increased characteristic intestinal permeability of children with atopic eczema and food allergy, (ii) can thus prevent the uptake of allergens, and (iii) finally can prevent the expression of the atopic constitution. The use of adequate probiotic lactobacilli, i.e., homolactic and/or facultatively heterolactic l-lactic acid-producing lactobacilli, reduces the intestinal amounts of the bacterial, toxic metabolites, d-lactic acid and ethanol by fermentative production of merely the non-toxic l-lactic acid from glucose. Thus, it is thought that beneficial probiotic micro-organisms promote gut barrier function and both undo and prevent unfavourable intestinal micro-ecological alterations in allergic individuals.

  3. Sustaining the Effects of Gatekeeper Suicide Prevention Training.

    Science.gov (United States)

    Shtivelband, Annette; Aloise-Young, Patricia A; Chen, Peter Y

    2015-02-23

    Background: Gatekeeper training is a promising suicide prevention strategy that is growing in popularity. Although gatekeeper training programs have been found to improve trainee knowledge, self-efficacy, and perceived skills, researchers have found that the benefit of gatekeeper training may not last over time. Aims: The purpose of this study was to identify strategies for strengthening the long-term effects of suicide prevention gatekeeper training. Method: In-depth interviews and focus groups were conducted with gatekeepers (N = 44) and data were analyzed using a qualitative research approach. Results: The results of this study suggest that posttraining interventions may be more effective if they include the following seven themes: (a) social network - connecting with other gatekeepers; (b) continued learning - further education; (c) community outreach - building awareness; (d) accessibility - convenience; (e) reminders - ongoing communication; (f) program improvement -- enhancing previous training; and (g) certification - accreditation. Conclusion: Posttraining interventions that incorporate the themes from this study offer a promising direction in which to sustain the effects of gatekeeper suicide prevention training.

  4. Effect of Chronic Restraint Stress on HPA Axis Activity and Expression of BDNF and Trkb in the Hippocampus of Pregnant Rats: Possible Contribution in Depression during Pregnancy and Postpartum Period

    Directory of Open Access Journals (Sweden)

    Nader maghsoudi

    2014-05-01

    Full Text Available Introduction: Brain-Derived Neurotrophic Factor (BDNF and its receptor, TrkB, in the hippocampus are targets for adverse effects of stress paradigms in addition, BDNF and its receptor play key role in the pathology of brain diseases like depression. In the present study, we evaluated the possible role of hippocampal BDNF in depression during pregnancy, Methods: To achieve the purpose, repeated restrain stress (1 or 3 hours daily for 7 days during the last week of pregnancy was used and alteration in the gene expression of hippocampal BDNF and TrkB evaluated by semi-quantitative PCR. Results: The results showed that in stress group the level of ACTH and Corticosterone is increased showing that our model was efficient in inducing psychological stress we also found that BDNF and TrkB expression are decreased in 3 hours stress group but not in 1 hour stress compared to control group. Discussion: Our results imply that decrease in BDNF and its receptor could contribute in some adverse effects of stress during pregnancy such as elevation of depressive like behavior.

  5. Memory of music: roles of right hippocampus and left inferior frontal gyrus.

    Science.gov (United States)

    Watanabe, Takamitsu; Yagishita, Sho; Kikyo, Hideyuki

    2008-01-01

    We investigated neural correlates of retrieval success for music memory using event-related functional magnetic resonance imaging. To minimize the interference from MRI scan noise, we used sparse temporal sampling technique. Newly composed music materials were employed as stimuli, which enabled us to detect regions in absence of effects of experience with the music stimuli in this study. Whole brain analyses demonstrated significant retrieval success activities in the right hippocampus, bilateral lateral temporal regions, left inferior frontal gyrus and left precuneus. Anatomically defined region-of-interests analyses showed that the activity of the right hippocampus was stronger than that of the left, while the activities of the inferior frontal gyri showed the reverse pattern. Furthermore, performance-based analyses demonstrated that the retrieval success activity of the right hippocampus was positively correlated with the corrected recognition rate, suggesting that the right hippocampus contributes to the accuracy of music retrieval outcome.

  6. Crisis Phones - Suicide Prevention Versus Suggestion/Contagion Effects.

    Science.gov (United States)

    Stack, Steven

    2015-01-01

    There has been no systematic work on the short- or long-term impact of the installation of crisis phones on suicides from bridges. The present study addresses this issue. Data refer to 219 suicides from 1954 through 2013 on the Skyway Bridge in St. Petersburg, Florida. Six crisis phones with signs were installed in July 1999. In the first decade after installation, the phones were used by 27 suicidal persons and credited with preventing 26 or 2.6 suicides a year. However, the net suicide count increased from 48 in the 13 years before installation of phones to 106 the following 13 years or by 4.5 additional suicides/year (t =3.512, p < .001). Although the phones prevented some suicides, there was a net increase after installation. The findings are interpreted with reference to suggestion/contagion effects including the emergence of a controversial bridge suicide blog.

  7. Fetal Alcohol Spectrum Disorders (FASD): an Approach to Effective Prevention.

    Science.gov (United States)

    Roozen, Sylvia; Black, D; Peters, G-J Y; Kok, G; Townend, D; Nijhuis, J G; Koek, G H; Curfs, L M G

    2016-01-01

    The objective of the current contribution is to propose an evidence-based, six-step approach to develop effective programs for prevention of fetal alcohol spectrum disorders. Despite widespread campaigns aimed to reduce prenatal alcohol exposure, the number of affected children continues to be high. Current strategies to reduce prenatal alcohol exposure may be ineffective or counterproductive. However, proven principles of health promotion could be applied to reduce drinking in pregnancy. One such approach is Intervention Mapping (IM), a six-step procedure based on proven principles to change behaviors. FASD affects all communities and is an underestimated problem worldwide. Programs based on proven principles of behavior change are warranted. Program developers can use pre-existing protocols and strategies from evidence-based practice, such as Intervention Mapping. Developers who plan their preventive programs in a systematic and evidence-based manner increase the chances of success in reducing prenatal alcohol exposure and FASD.

  8. Can chaos theory be used to increase preventive maintenance effectiveness?

    Science.gov (United States)

    Rice, W P

    1996-01-01

    Clinical engineering programs typically establish the content and frequency of a device's inspection and preventive maintenance procedures at the time of implementation. In some programs, these are not altered throughout the device's useful life. In others, history data and traditional statistical methods are used to adapt procedures to change in risk measures. Such methods are essentially reactive in that they are based upon past trends and do not readily consider potentialities for future change in the performance and utilization environments. Chaos theoretical concepts and related measures, when implemented in artificial intelligence programs such as neural networks and genetic algorithms, and used as an adjunct with computerized technology management programs, can assist in asking and answering the more dynamic, proactive questions necessary for effective inspection and preventive maintenance optimization. Today's healthcare environment is ideal for exploring their utilization.

  9. What Representations and Computations Underpin the Contribution of the Hippocampus to Generalization and Inference?

    Directory of Open Access Journals (Sweden)

    Dharshan eKumaran

    2012-06-01

    Full Text Available Empirical research and theoretical accounts have traditionally emphasized the function of the hippocampus in episodic memory. Here we draw attention to the importance of the hippocampus to generalization, and focus on the neural representations and computations that might underpin its role in tasks such as the paired associate inference paradigm. We make a principal distinction between two different mechanisms by which the hippocampus may support generalization: an encoding-based mechanism that creates overlapping representations that capture higher-order relationships between different items (e.g. TCM – and a retrieval-based model (REMERGE that effectively computes these relationships at the point of retrieval, through a recurrent mechanism that allows the dynamic interaction of multiple pattern separated episodic codes. We also discuss what we refer to as transfer effects - a more abstract example of generalization that has also been linked to the function of the hippocampus. We consider how this phenomenon poses inherent challenges for models such as TCM and REMERGE, and outline the potential applicability of a separate class of models - hierarchical bayesian models (HBMs in this context. Our hope is that this article will provide a basic framework within which to consider the theoretical mechanisms underlying the role of the hippocampus in generalization, and at a minimum serve as a stimulus for future work addressing issues that go to the heart of the function of the hippocampus.

  10. Gonadectomy increases neurogenesis in the male adolescent rhesus macaque hippocampus.

    Science.gov (United States)

    Allen, K M; Fung, S J; Rothmond, D A; Noble, P L; Weickert, C Shannon

    2014-02-01

    New neurons are continuously produced in the subgranular zone of the adult hippocampus and can modulate hippocampal plasticity across life. Adolescence is characterized by dramatic changes in sex hormone levels, and social and emotional behaviors. It is also an age for increased risk of psychiatric disorders, including schizophrenia, which may involve altered hippocampal neurogenesis. The extent to which testosterone and other testicular hormones modulate hippocampal neurogenesis and adolescent behavioral development is unclear. This study aimed to determine if removal of testicular hormones during adolescence alters neurogenesis in the male rhesus macaque hippocampus. We used stereology to examine levels of cell proliferation, cell survival and neuronal differentiation in late adolescent male rhesus macaques (4.6-yrs old) that had previously been gonadectomized or sham operated prior to puberty (2.4-yrs old). While the absence of adolescent testicular hormones had no effect on cell proliferation, cell survival was increased by 65% and indices of immature neuronal differentiation were increased by 56% in gonadectomized monkeys compared to intact monkeys. We show for the first time that presence of circulating testicular hormones, including testosterone, may decrease neuronal survival in the primate hippocampus during adolescence. Our findings are in contrast to existing studies in adults where testosterone tends to be a pro-survival factor and demonstrate that testicular hormones may reduce hippocampal neurogenesis during the age typical of schizophrenia onset. Copyright © 2013 Wiley Periodicals, Inc.

  11. Effects of probiotics on the prevention of atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Nam Yeun Kim

    2012-06-01

    Full Text Available Atopic dermatitis (AD is an immune disorder that is becoming increasingly prevalent throughout the world. The exact etiology of AD remains unknown, and a cure for AD is not currently available. The hypothesis that appropriate early microbial stimulation contributes to the establishment of a balanced immune system in terms of T helper type Th1, Th2, and regulatory T cell (Treg responses has led to the use of probiotics for the prevention and treatment of AD in light of various human clinical studies and animal experiments. Meta-analysis data suggests that probiotics can alleviate the symptoms of AD in infants. The effects of balancing Th1/Th2 immunity and enhancing Treg activity via the interaction of probiotics with dendritic cells have been described &lt;em&gt;in vitro&lt;/em&gt; and in animal models, although such an effect has not been demonstrated in human studies. In this review, we present some highlights of the immunomodulatory effects of probiotics in humans and animal studies with regard to their effects on the prevention of AD.

  12. Gestational diabetes mellitus: does an effective prevention strategy exist?

    Science.gov (United States)

    Agha-Jaffar, Rochan; Oliver, Nick; Johnston, Desmond; Robinson, Stephen

    2016-09-01

    The overall incidence of gestational diabetes mellitus (GDM) is increasing worldwide. Preventing pathological hyperglycaemia during pregnancy could have several benefits: a reduction in the immediate adverse outcomes during pregnancy, a reduced risk of long-term sequelae and a decrease in the economic burden to healthcare systems. In this Review we examine the evidence supporting lifestyle modification strategies in women with and without risk factors for GDM, and the efficacy of dietary supplementation and pharmacological approaches to prevent this disease. A high degree of heterogeneity exists between trials so a generalised recommendation is problematic. In population studies of dietary or combined lifestyle measures, risk of developing GDM is not improved and those involving a physical activity intervention have yielded conflicting results. In pregnant women with obesity, dietary modification might reduce fetal macrosomia but in these patients, low compliance and no significant reduction in the incidence of GDM has been observed in trials investigating physical activity. Supplementation with probiotics or myoinositol have reduced the incidence of GDM but confirmatory studies are still needed. In randomized controlled trials, metformin does not prevent GDM in certain at-risk groups. Given the considerable potential for reducing disease burden, further research is needed to identify strategies that can be easily and effectively implemented on a population level.

  13. Sex, hormones and neurogenesis in the hippocampus: hormonal modulation of neurogenesis and potential functional implications.

    Science.gov (United States)

    Galea, L A M; Wainwright, S R; Roes, M M; Duarte-Guterman, P; Chow, C; Hamson, D K

    2013-11-01

    The hippocampus is an area of the brain that undergoes dramatic plasticity in response to experience and hormone exposure. The hippocampus retains the ability to produce new neurones in most mammalian species and is a structure that is targeted in a number of neurodegenerative and neuropsychiatric diseases, many of which are influenced by both sex and sex hormone exposure. Intriguingly, gonadal and adrenal hormones affect the structure and function of the hippocampus differently in males and females. Adult neurogenesis in the hippocampus is regulated by both gonadal and adrenal hormones in a sex- and experience-dependent way. Sex differences in the effects of steroid hormones to modulate hippocampal plasticity should not be completely unexpected because the physiology of males and females is different, with the most notable difference being that females gestate and nurse the offspring. Furthermore, reproductive experience (i.e. pregnancy and mothering) results in permanent changes to the maternal brain, including the hippocampus. This review outlines the ability of gonadal and stress hormones to modulate multiple aspects of neurogenesis (cell proliferation and cell survival) in both male and female rodents. The function of adult neurogenesis in the hippocampus is linked to spatial memory and depression, and the present review provides early evidence of the functional links between the hormonal modulation of neurogenesis that may contribute to the regulation of cognition and stress. © 2013 British Society for Neuroendocrinology.

  14. The Role of Hippocampus in the Pathophysiology of Depression

    Directory of Open Access Journals (Sweden)

    Özlem Donat Eker

    2009-06-01

    Full Text Available Hippocampus, as a part of the limbic cortex, has a variety of functions ranging from mating behavior to memory besides its role in the regulation of emotions. The hippocampus has reciprocal interactions of with other brain regions which act in the pathophysiology of major depressive disorder (MDD. Moreover, since the hippocampus is a scene for the neurogenesis, which can be seen as a response to antidepressant treatment, the hippocampus became a focus of attention in neuroimaging studies of MDD. It has been shown that brain derived neurotrophic factor (BDNF, that is responsible from the neurogenesis, is associated with the response to the antidepressants and antidepressant drugs are ineffective if neurogenesis is hindered.Hippocampal atrophy is expected with the decrease of neurogenesis as a result of the lower BDNF levels with the deleterious effects of glucocorticoids in depression. Recurrent and severe depression seems to cause such a volume reduction though first episode MDD subjects do not differ from healthy individuals in respect to their hippocampal volumes (HCVs measured by magnetic resonance imaging methods. One may argue regarding these findings that the atrophy in the hippocampus may be observed in the long term and the decrease in BDNF levels may predispose the volume reduction. Although it has been postulated that smaller HCV as a result of genetic and environmental factors and prior to the illness, may cause a vulnerability to MDD, sufficient evidence has not been accumulated yet and the view that HCV loss develops as depression progresses is widely accepted. Findings that serum BDNF (sBDNF is lower in MDD patients though HCVs of patients do not differ from healthy individuals and the positive correlation of sBDNF with HCV seen only in the patient group support this view. It can be assumed that depressed patients have sensitivity for the fluctuations in BDNF levels. Follow-up studies which consider effects of hipotalamo

  15. [Preventive effects of pueraria on presbycusis in rats].

    Science.gov (United States)

    Chen, Wangyan; Yao, Qi; Liu, Weihong; Zhang, Bibo; Wang, Ying; Liu, Bo

    2009-08-01

    To investigate the preventive effects of Pueraria on presbycusis in rats. Thirty-two 24-26 month old Wistar rats were randomly divided into four groups, and were treated with different dosages of Pueraria (1, 2, 4, 0 g x kg(-1) x d(-1)) separately for 4 weeks. Auditory brainstem response (ABR) was used to detect the change of hearing threshold of rats. Hemorheological items of rats were checked in each group. Compared with control group, the hearing threshold and hemorheological items of rats was significantly improved after treated with Pueraria (Ppresbycusis of rats.

  16. Preventive Effects of Houttuynia cordata Extract for Oral Infectious Diseases

    Directory of Open Access Journals (Sweden)

    Yasuko Sekita

    2016-01-01

    Full Text Available Houttuynia cordata (HC (Saururaceae has been used internally and externally as a traditional medicine and as an herbal tea for healthcare in Japan. Our recent survey showed that HC poultice (HCP prepared from smothering fresh leaves of HC had been frequently used for the treatment of purulent skin diseases with high effectiveness. Our experimental study also demonstrated that ethanol extract of HCP (eHCP has antibacterial, antibiofilm, and anti-inflammatory effects against S. aureus which caused purulent skin diseases. In this study, we focused on novel effects of HCP against oral infectious diseases, such as periodontal disease and dental caries. We determined the antimicrobial and antibiofilm effects of water solution of HCP ethanol extract (wHCP against important oral pathogens and investigated its cytotoxicity and anti-inflammatory effects on human oral epithelial cells. wHCP had moderate antimicrobial effects against some oral microorganisms and profound antibiofilm effects against Fusobacterium nucleatum, Streptococcus mutans, and Candida albicans. In addition, wHCP had no cytotoxic effects and could inhibit interleukin-8 and CCL20 productions by Porphyromonas gingivalis lipopolysaccharide-stimulated human oral keratinocytes. Our findings suggested that wHCP may be clinically useful for preventing oral infectious diseases as a mouthwash for oral care.

  17. Prevention of dipyrone (metamizole) induced inhibition of aspirin antiplatelet effects.

    Science.gov (United States)

    Polzin, Amin; Richter, Stefan; Schrör, Karsten; Rassaf, Tienush; Merx, Marc W; Kelm, Malte; Hohlfeld, Thomas; Zeus, Tobias

    2015-07-01

    We have recently shown that dipyrone (metamizole), a non-opioid analgesic, can nullify aspirin (acetylsalicylic acid; ASA) antiplatelet effects in patients with coronary artery disease (CAD). In this study, we analysed the aspirin and dipyrone drug-drug interaction in order to identify strategies to prevent the dipyrone induced inhibition of asprin antiplatelet effects. Platelet function was measured by arachidonic acid-induced light-transmission aggregometry, thromboxane (TX) B2- formation by immunoassay. Dipyrone metabolite plasma levels were determined by high-performance-liquid-chromatography (HPLC). In seven healthy individuals, in vitro ASA (30 µM/ 100 µM/ 300 µM/ 1,000 µM) and dipyrone (10 µM) coincubation revealed, that the aspirin and dipyrone interaction can be overcome by increasing doses of aspirin. In 36 aspirin and dipyrone comedicated CAD patients, addition of ASA (30 µM/ 100 µM) in vitro inhibited, but did not completely overcome the dipyrone induced reduction of aspirin antiplatelet effects. Notably, the inhibition of thromboxane formation in aspirin and dipyrone comedicated CAD patients coincided with dipyrone plasma levels. In a cross-over designed study in four healthy individuals, we were able to prove that inhibition of aspirin (100 mg/ day) effects by dipyrone (750 mg/ day) was reversible. Furthermore, aspirin (100 mg/ day) medication prior to dipyrone (750 mg/ day) intake prevented the inhibition of antiplatelet effects by dipyrone in 12 healthy individuals. In conclusion, aspirin medication prior to dipyrone intake preserves antiplatelet effects, circumventing the pharmacodynamic drug-drug interaction at the level of cyclooxygenase-1.

  18. Reviewing the evidence on effectiveness and cost-effectiveness of HIV prevention strategies in Thailand

    Directory of Open Access Journals (Sweden)

    Teerawattananon Yot

    2010-07-01

    Full Text Available Abstract Background Following universal access to antiretroviral therapy in Thailand, evidence from National AIDS Spending Assessment indicates a decreasing proportion of expenditure on prevention interventions. To prompt policymakers to revitalize HIV prevention, this study identifies a comprehensive list of HIV/AIDs preventive interventions that are likely to be effective and cost-effective in Thailand. Methods A systematic review of the national and international literature on HIV prevention strategies from 1997 to 2008 was undertaken. The outcomes used to consider the effectiveness of HIV prevention interventions were changes in HIV risk behaviour and HIV incidence. Economic evaluations that presented their results in terms of cost per HIV infection averted or cost per quality-adjusted life year (QALY gained were also included. All studies were assessed against quality criteria. Results The findings demonstrated that school based-sex education plus life-skill programs, voluntary and routine HIV counselling and testing, male condoms, street outreach programs, needle and syringe programs, programs for the prevention of mother-to-child HIV transmission, male circumcision, screening blood products and donated organs for HIV, and increased alcohol tax were all effective in reducing HIV infection among target populations in a cost-effective manner. Conclusion We found very limited local evidence regarding the effectiveness of HIV interventions amongst specific high risk populations. This underlines the urgent need to prioritise health research resources to assess the effectiveness and cost-effectiveness of HIV interventions aimed at reducing HIV infection among high risk groups in Thailand.

  19. Organised Crime Prevention in the Netherlands: Exposing the Effectiveness of Preventive Measures

    OpenAIRE

    Schoot, C.R.A.

    2006-01-01

    textabstractThe preventive approach against organised crime has gained much attention since the early 1990s. On an international level as well as on a national one various preventive measures against organised crime have been developed. This is certainly true in the European Union and the Netherlands. This introduction chapter is divided into three sections. The first looks at the developments that led to the preventive approach to organised crime, focusing on the growing enthusiasm for the p...

  20. Effects of the Natural β-Carboline Alkaloid Harmine, a Main Constituent of Ayahuasca, in Memory and in the Hippocampus: A Systematic Literature Review of Preclinical Studies.

    Science.gov (United States)

    Dos Santos, Rafael G; Hallak, Jaime E C

    2017-01-01

    Harmine is a natural β-carboline alkaloid found in several botanical species, such as the Banisteriopsis caapi vine used in the preparation of the hallucinogenic beverage ayahuasca and the seeds of Syrian rue (Peganum harmala). Preclinical studies suggest that harmine may have neuroprotective and cognitive-enhancing effects, and retrospective/observational investigations of the mental health of long-term ayahuasca users suggest that prolonged use of this harmine-rich hallucinogen is associated with better neuropsychological functioning. Thus, in order to better investigate these possibilities, we performed a systematic literature review of preclinical studies analyzing the effects of harmine on hippocampal neurons and in memory-related behavioral tasks in animal models. We found two studies involving hippocampal cell cultures and nine studies using animal models. Harmine administration was associated with neuroprotective effects such as reduced excitotoxicity, inflammation, and oxidative stress, and increased brain-derived neurotrophic factor (BDNF) levels. Harmine also improved memory/learning in several animal models. These effects seem be mediated by monoamine oxidase or acetylcholinesterase inhibition, upregulation of glutamate transporters, decreases in reactive oxygen species, increases in neurotrophic factors, and anti-inflammatory effects. The neuroprotective and cognitive-enhancing effects of harmine should be further investigated in both preclinical and human studies.

  1. Preventable complications in epilepsy admissions: The "July effect".

    Science.gov (United States)

    Pierson, Natalie S; Kramer, Daniel R; Wen, Timothy; Ho, Lianne; Patel, Arati; Donoho, Daniel; Mehta, Vivek; Heck, Christianne; Lee, Brian; Mack, William J; Liu, Charles Y

    2017-11-01

    Inpatient hospital stays for patients with epilepsy represent a significant burden on patients and society. Identifying factors that contribute to such costs aides in developing effective strategies to address this burden. July admissions have been associated with higher rates of complications and worse outcomes, attributed to the presence of new physicians. This study aims to evaluate whether epilepsy patients admitted in July have higher preventable complication rates and mortality than during the rest of the year. Data was derived from the Nationwide Inpatient Sample (NIS) for epilepsy admissions for the years 2000-2010. Multivariable analyses assessed the effect of July against non-July admission on "hospital acquired complications" (HAC), which are complications identified as owing to preventable causes and mortality. Additionally, the total adjusted charges and prolonged length of stay (pLOS) for July admissions were compared to the 50th percentile. A total of 12,997,181 admissions for epilepsy were identified with 993,619 (8%) occurring in July, 10,810,900 (83%) were non-July months, and 1,192,662 (9%) were missing data. Patients admitted in July showed an increased association for HAC events (RR=1.02, [1.01,1.03], pepilepsy population, although July admissions were associated with a slight increase in HAC events, there was a non-significant or decreased rate of mortality, LOS, and total charge. Our results suggest that although complications were increased in July, possibly due to new staff, supervision is sufficient to prevent significant burden on patients and hospitals. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Acute treatment with doxorubicin affects glutamate neurotransmission in the mouse frontal cortex and hippocampus.

    Science.gov (United States)

    Thomas, Theresa Currier; Beitchman, Joshua A; Pomerleau, Francois; Noel, Teresa; Jungsuwadee, Paiboon; Allan Butterfield, D; Clair, Daret K St; Vore, Mary; Gerhardt, Greg A

    2017-10-01

    Doxorubicin (DOX) is a potent chemotherapeutic agent known to cause acute and long-term cognitive impairments in cancer patients. Cognitive function is presumed to be primarily mediated by neuronal circuitry in the frontal cortex (FC) and hippocampus, where glutamate is the primary excitatory neurotransmitter. Mice treated with DOX (25mg/kg i.p.) were subjected to in vivo recordings under urethane anesthesia at 24h post-DOX injection or 5 consecutive days of cognitive testing (Morris Water Maze; MWM). Using novel glutamate-selective microelectrode arrays, amperometric recordings measured parameters of extracellular glutamate clearance and potassium-evoked release of glutamate within the medial FC and dentate gyrus (DG) of the hippocampus. By 24h post-DOX injection, glutamate uptake was 45% slower in the FC in comparison to saline-treated mice. In the DG, glutamate took 48% longer to clear than saline-treated mice. Glutamate overflow in the FC was similar between treatment groups, however, it was significantly increased in the DG of DOX treated mice. MWM data indicated that a single dose of DOX impaired swim speed without impacting total length traveled. These data indicate that systemic DOX treatment changes glutamate neurotransmission in key nuclei associated with cognitive function within 24h, without a lasting impact on spatial learning and memory. Understanding the functional effects of DOX on glutamate neurotransmission may help us understand and prevent some of the debilitating side effects of chemotherapeutic treatment in cancer survivors. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Micronutrient deficiencies in pregnancy worldwide: health effects and prevention

    Science.gov (United States)

    Gernand, Alison D.; Schulze, Kerry J.; Stewart, Christine P.; West, Keith P.; Christian, Parul

    2016-01-01

    Micronutrients, vitamins and minerals accessible from the diet, are essential for biologic activity. Micronutrient status varies widely throughout pregnancy and across populations. Women in low-income countries often enter pregnancy malnourished, and the demands of gestation can exacerbate micronutrient deficiencies with health consequences to the fetus. Examples of efficacious single micronutrient interventions include folic acid to prevent neural tube defects, iodine to prevent cretinism, zinc to reduce of preterm birth, and iron to reduce the risk of low birth weight. Folic acid and vitamin D might also increase birth weight. While extensive mechanism and association research links antenatal multiple micronutrients to plausible materno-fetal health advantages, hypothesized benefits have often been absent, minimal or unexpected in trials. These findings suggest a role for population context in determining health responses and extensive gaps in knowledge. Multiple micronutrient supplements reduce risks of being born low birth weight, small for gestational age or stillborn in undernourished settings, and justify micronutrient interventions with antenatal care. Measurable health effects of gestational micronutrient exposure may persist into childhood but few data exists on potential long-term benefits. In this Review, we discuss micronutrient intake recommendations, risks and consequences of deficiencies, and the effects of interventions with a particular emphasis on offspring. PMID:27032981

  4. Effectiveness of Mindfulness-Based Relapse Prevention in opioid Dependence Treatment &Mental Health

    Directory of Open Access Journals (Sweden)

    2008-11-01

    Findings: therapy compliance, retention in treatment, decrease in somatic symptoms, anxiety, social dysfunction and increase in health was significantly in both combination of psychological intervention method than the Naltroxan group. Mindfulness-based on relapse prevention was more effective than CBT relapse prevention in decreasing of, social dysfunction, relapse prevention, increase of therapy compliance, and health. Results: Mindfulness based relapse prevention was superior to CBT and Naltroxan and considerably increased effectiveness of opioid relapse prevention therapy.

  5. Coordinating different representations in the hippocampus

    Czech Academy of Sciences Publication Activity Database

    Kelemen, Eduard; Fenton, A.A.

    2016-01-01

    Roč. 129, Mar 2016 (2016), s. 50-59 ISSN 1074-7427 R&D Projects: GA ČR(CZ) GA14-03627S Institutional support: RVO:67985823 Keywords : dynamic functional grouping * multiple representations * cognitive control * hippocampus * overdispersion Subject RIV: FH - Neurology Impact factor: 3.543, year: 2016

  6. Mind-body problem and hippocampus.

    Science.gov (United States)

    Behrendt, Ralf-Peter

    2017-09-01

    Commentary on Faw's comprehensive response to a previous commentary ('Hippocampus as a wormhole' by Ralf-Peter Behrendt, doi: 10.1002/wcs.1446) on Faw and Faw's paper (doi: 10.1002/wcs.1412). WIREs Cogn Sci 2017, e1447. doi: 10.1002/wcs.1447. © 2017 Wiley Periodicals, Inc.

  7. Mnemonic convergence in the human hippocampus

    NARCIS (Netherlands)

    Backus, A.R.; Bosch, S.E.; Ekman, M.; Vicente-Grabovetsky, A.; Doeller, C.F.

    2016-01-01

    The ability to form associations between a multitude of events is the hallmark of episodic memory. Computational models have espoused the importance of the hippocampus as convergence zone, binding different aspects of an episode into a coherent representation, by integrating information from

  8. Effects of Glycyrrhetinic Acid on GSH Synthesis Induced by Realgar in the Mouse Hippocampus: Involvement of System [Formula: see text], System [Formula: see text], MRP-1, and Nrf2.

    Science.gov (United States)

    Wang, Yan-Lei; Chen, Mo; Huo, Tao-Guang; Zhang, Ying-Hua; Fang, Ying; Feng, Cong; Wang, Shou-Yun; Jiang, Hong

    2017-05-01

    Realgar, a type of mineral drug-containing arsenic, exhibits neurotoxicity. Brain glutathione (GSH) is crucial to protect the nervous system and to resist arsenic toxicity. Therefore, the main aim of this study was to explore the neurotoxic mechanisms of realgar and the protective effects of glycyrrhetinic acid (GA) by observing the effects of GA on the hippocampal GSH biosynthetic pathway after exposure to realgar. Institute of Cancer Research (ICR) mice were randomly divided into five groups: a control group, a GA control group, a realgar alone group, a low-dose GA intervention group, and a high-dose GA intervention group. Cognitive ability was tested using an object recognition task (ORT). The ultrastructures of the hippocampal neurons and synapses were observed. mRNA and protein levels of EAAT1, EAAT2, EAAT3, xCT, Nrf2, HO-1, γ-GCS (GCLC, GCLM), and MRP-1 were measured, as was the cellular localization of EAAT3, xCT, MRP-1, and Nrf2. The levels of GSH in the hippocampus, the levels of glutamate (Glu) and cysteine (Cys) in the extracellular fluid of hippocampal CA1 region, and the levels of active sulfur in the brain were also investigated. The results indicate that realgar lowered hippocampal GSH levels, resulting in ultrastructural changes in hippocampal neurons and synapses and deficiencies in cognitive ability, ultimately inducing neurotoxicity. GA could trigger the expression of Nrf2, HO-1, EAAT1, EAAT2, EAAT3, xCT, MRP-1, GCLC, and GCLM. Additionally, the expression of γ-GT and the supply levels of Glu and Cys increased, ultimately causing a significant increase in hippocampal GSH to alleviate realgar-induced neurotoxicity. In conclusion, the findings from our study indicate that GA can antagonize decreased brain GSH levels induced by realgar and can lessen the neurotoxicity of realgar.

  9. Organised Crime Prevention in the Netherlands: Exposing the Effectiveness of Preventive Measures

    NARCIS (Netherlands)

    C.R.A. van der Schoot

    2006-01-01

    textabstractThe preventive approach against organised crime has gained much attention since the early 1990s. On an international level as well as on a national one various preventive measures against organised crime have been developed. This is certainly true in the European Union and the

  10. [Adverse effects of intravenous arsenic trioxide and their prevention].

    Science.gov (United States)

    Wu, Nan; Hu, Long-hu; Zhou, Jin; Fan, Sheng-jin; Wang, Yan; Han, Xue-ying

    2006-04-01

    To study the main side effects of As(2)O(3) and the way of prevention. The changes of body weight and various systems of body were observed after treatment with As(2)O(3) injection. The arsenic content in blood, urine and hair was detected with atom absorbed-spectrum analysis. Mild reactions were observed in 57.43% (147/256) of the patients and they could subside after cessation of arsenic treatment or allotherapy. Chronic mild poisoning manifestations including arsenic furuncle, liver dysfunction and peripheral nerve injury were found in 2.73% (7/256) of the patients and they subsided gradually after treatment. Chronic severe poisoning was found in 1.17% of the patients and all of them died of liver failure. As(2)O(3) might cause decrease of peripheral blood WBC in catabatic patients. There was no infection after allopathy without ceasing arsenic medication. The results showed that As(2)O(3) could distribute over and discharge from the plasma without accumulation in blood. The results also demonstrated the main route of excretion for As(2)O(3) is through urine and there is definite accumulation in the hair 50 days after treatment. Most of the side effects of As(2)O(3) are mild and recoverable. Allotherapy could be effective to relieve the complications without stopping arsenic medication. A few patients with complicating hepatitis may suffer from chronic poisoning. As(2)O(3) may cause increase of peripheral blood WBC in induced catabatic APL patients. The side effects must be prevented early.

  11. A Key Role for Nectin-1 in the Ventral Hippocampus in Contextual Fear Memory

    Science.gov (United States)

    Grosse, Jocelyn; Krummenacher, Claude; Sandi, Carmen

    2013-01-01

    Nectins are cell adhesion molecules that are widely expressed in the brain. Nectin expression shows a dynamic spatiotemporal regulation, playing a role in neural migratory processes during development. Nectin-1 and nectin-3 and their heterophilic trans-interactions are important for the proper formation of synapses. In the hippocampus, nectin-1 and nectin-3 localize at puncta adherentia junctions and may play a role in synaptic plasticity, a mechanism essential for memory and learning. We evaluated the potential involvement of nectin-1 and nectin-3 in memory consolidation using an emotional learning paradigm. Rats trained for contextual fear conditioning showed transient nectin-1—but not nectin-3—protein upregulation in synapse-enriched hippocampal fractions at about 2 h posttraining. The upregulation of nectin-1 was found exclusively in the ventral hippocampus and was apparent in the synaptoneurosomal fraction. This upregulation was induced by contextual fear conditioning but not by exposure to context or shock alone. When an antibody against nectin-1, R165, was infused in the ventral-hippocampus immediately after training, contextual fear memory was impaired. However, treatment with the antibody in the dorsal hippocampus had no effect in contextual fear memory formation. Similarly, treatment with the antibody in the ventral hippocampus did not interfere with acoustic memory formation. Further control experiments indicated that the effects of ventral hippocampal infusion of the nectin-1 antibody in contextual fear memory cannot be ascribed to memory non-specific effects such as changes in anxiety-like behavior or locomotor behavior. Therefore, we conclude that nectin-1 recruitment to the perisynaptic environment in the ventral hippocampus plays an important role in the formation of contextual fear memories. Our results suggest that these mechanisms could be involved in the connection of emotional and contextual information processed in the amygdala and dorsal

  12. The effects of short-term chronic ethanol intoxication and ethanol withdrawal on the molecular composition of the rat hippocampus by FT-IR spectroscopy.

    Science.gov (United States)

    Elibol-Can, Birsen; Jakubowska-Dogru, Ewa; Severcan, Mete; Severcan, Feride

    2011-11-01

    The numerous adverse effects of ethanol abuse and ethanol withdrawal on biological systems are well documented. Conversely, the understanding of the molecular mechanisms underlying these pathological effects is still incomplete. This study was undertaken to investigate the effects of short-term chronic ethanol administration and ethanol withdrawal on the molecular structure and function of hippocampal tissue, a brain region important for mnemonic processes and known to be highly susceptible to ethanol intoxication. Ethanol was administered to adult Wistar rats by intragastric intubation for 15 days with a stepwise increase in the daily dose from 6 to 12 g/kg body weight, with the highest dose delivered for the last 2 days only. The total daily dose of ethanol was divided into 3 equal portions administered 4 hours apart. Animals were sacrificed by decapitation at 4, 24, and 72 hours after the last ethanol administration to examine potential effects of ethanol intoxication and ethanol withdrawal. Ethanol-related molecular changes were monitored by Fourier transform infrared (FT-IR) spectroscopy. Significant changes in the hippocampal content, structure, and function of lipids, proteins, and nucleic acids were recorded under ethanol intoxication. Seventy-two hours after the cessation of ethanol administration, during the late phase of withdrawal, alterations in the macromolecules' content and conformational changes in protein and nucleic acid structure ameliorated, while the changes in macromolecular ratios, lipid order, and dynamics aggravated. Our results suggest that 15 days of binge-like drinking resulting in the high blood alcohol concentration (varying in the dose-dependent manner between 253 and 606 mg/dl) produced a strong physical dependence manifested mainly by the changes in lipid profiles pointing toward withdrawal-induced oxidative stress. These results show that ethanol withdrawal may cause equal to or even more severe brain damage than the ethanol

  13. Protective effect of systemic L-kynurenine and probenecid administration on behavioural and morphological alterations induced by toxic soluble amyloid beta (25-35) in rat hippocampus.

    Science.gov (United States)

    Carrillo-Mora, Paul; Méndez-Cuesta, Luis A; Pérez-De La Cruz, Verónica; Fortoul-van Der Goes, Teresa I; Santamaría, Abel

    2010-07-11

    Amyloid beta (Abeta) peptide exerts different toxic effects at a cellular level, including over-activation of N-methyl-D-aspartate receptor (NMDAr) and excitotoxicity, synaptic dysfunction and neuronal death. Kynurenic acid (KYNA) is an endogenous antagonist of NMDAr and alpha7 nicotinic receptors. Systemic administrations of both the immediate metabolic precursor of KYNA, L-kynurenine (L-KYN), and a proved inhibitor of KYNA's brain transport, probenecid (PROB), have shown to produce neuroprotective effects in a considerable number of experimental toxic conditions; however, this strategy has not been tested in the toxic model Abeta peptide so far. In this study we evaluated the effects of systemic administration of PROB (50 mg/kg/day for 7 days), L-KYN (75 mg/kg/day for 7 days) and their combination, on behavioural (locomotor activity and spatial memory) and morphological alterations induced by an intrahippocampal infusion of Abeta 25-35 to rats. An additional group was administered with the potent NMDAr antagonist dizocilpine (MK-801, 0.8 mg/kg/day for 7 days) for comparative purposes. A significant improvement of spatial memory was evident in Abeta-lesioned rats since post-lesion day 21 with all treatments tested and this effect was correlated with a reduction of cell damage and a decrease in reactive gliosis in hippocampal CA1 area. Neither L-KYN, nor PROB, or their combination, produced major alterations in motor function when given alone to rats. These results suggest that modulation of NMDAr activity by mean of therapeutic strategies designed to enhance KYNA in the brain may help to counteract neurodegenerative events coursing with Abeta toxicity and excitotoxic patterns. Copyright 2010 Elsevier B.V. All rights reserved.

  14. Maternal dietary loads of alpha-tocopherol increase synapse density and glial synaptic coverage in the hippocampus of adult offspring

    Directory of Open Access Journals (Sweden)

    S. Salucci

    2014-05-01

    Full Text Available An increased intake of the antioxidant α-Tocopherol (vitamin E is recommended in complicated pregnancies, to prevent free radical damage to mother and fetus. However, the anti-PKC and antimitotic activity of α-Tocopherol raises concerns about its potential effects on brain development. Recently, we found that maternal dietary loads of α-Tocopherol through pregnancy and lactation cause developmental deficit in hippocampal synaptic plasticity in rat offspring. The defect persisted into adulthood, with behavioral alterations in hippocampus-dependent learning. Here, using the same rat model of maternal supplementation, ultrastructural morphometric studies were carried out to provide mechanistic interpretation to such a functional impairment in adult offspring by the occurrence of long-term changes in density and morphological features of hippocampal synapses. Higher density of axo-spinous synapses was found in CA1 stratum radiatum of α-Tocopherol-exposed rats compared to controls, pointing to a reduced synapse pruning. No morphometric changes were found in synaptic ultrastructural features, i.e., perimeter of axon terminals, length of synaptic specializations, extension of bouton-spine contact. Glia-synapse anatomical relationship was also affected. Heavier astrocytic coverage of synapses was observed in Tocopherol-treated offspring, notably surrounding axon terminals; moreover, the percentage of synapses contacted by astrocytic endfeet at bouton-spine interface (tripartite synapses was increased. These findings indicate that gestational and neonatal exposure to supranutritional tocopherol intake can result in anatomical changes of offspring hippocampus that last through adulthood. These include a surplus of axo-spinous synapses and an aberrant glia-synapse relationship, which may represent the morphological signature of previously described alterations in synaptic plasticity and hippocampus-dependent learning.

  15. Traveling Theta Waves in the Human Hippocampus

    Science.gov (United States)

    Zhang, Honghui

    2015-01-01

    The hippocampal theta oscillation is strongly correlated with behaviors such as memory and spatial navigation, but we do not understand its specific functional role. One hint of theta's function came from the discovery in rodents that theta oscillations are traveling waves that allow parts of the hippocampus to simultaneously exhibit separate oscillatory phases. Because hippocampal theta oscillations in humans have different properties compared with rodents, we examined these signals directly using multielectrode recordings from neurosurgical patients. Our findings confirm that human hippocampal theta oscillations are traveling waves, but also show that these oscillations appear at a broader range of frequencies compared with rodents. Human traveling waves showed a distinctive pattern of spatial propagation such that there is a consistent phase spread across the hippocampus regardless of the oscillations' frequency. This suggests that traveling theta oscillations are important functionally in humans because they coordinate phase coding throughout the hippocampus in a consistent manner. SIGNIFICANCE STATEMENT We show for the first time in humans that hippocampal theta oscillations are traveling waves, moving along the length of the hippocampus in a posterior–anterior direction. The existence of these traveling theta waves is important for understanding hippocampal neural coding because they cause neurons at separate positions in the hippocampus to experience different theta phases simultaneously. The theta phase that a neuron measures is a key factor in how that cell represents behavioral information. Therefore, the existence of traveling theta waves indicates that, to fully understand how a hippocampal neuron represents information, it is vital to also account for that cell's location in addition to conventional measures of neural activity. PMID:26354915

  16. THERAPEUTIC EFFECTS OF THE TRANSPLANTATION OF VEGF OVEREXPRESSING BONE MARROW MESENCHYMAL STEM CELLS IN THE HIPPOCAMPUS OF MURINE MODEL OF ALZHEIMER’S DISEASE

    Directory of Open Access Journals (Sweden)

    Karina de Oliveira Garcia

    2014-03-01

    Full Text Available Alzheimer´s disease (AD is clinically characterized by progressive memory loss, behavioural and learning dysfunction and cognitive deficits, such as alterations in social interactions. The major pathological features of AD are the formation of senile plaques and neurofibrillary tangles together with neuronal and vascular damage. The double transgenic mouse model of AD (2xTg-AD with the APPswe/PS1dE9 mutations shows characteristics that are similar to those observed in AD patients, including social memory impairment, senile plaque formation and vascular deficits. Mesenchymal stem cells (MSCs, when transplanted into the brain, produce positive effects by reducing Aβ deposition in transgenic APP/PS1 mice. Vascular endothelial growth factor (VEGF, exhibits neuroprotective effects against the excitotoxicity implicated in the AD neurodegeneration.The present study investigates the effects of MSCs overexpressing VEGF in hippocampal neovascularization, cognitive dysfunction and senile plaques present in 2xTg-AD transgenic mice. MSC were transfected with uP-VEGF vector, by electroporation and expanded at the 14th passage. 2xTg-AD animals at 6, 9 and 12 months old were transplanted with MSC-VEGF or MSC. The animals were tested for behavioral tasks to access locomotion, novelty exploration, learning and memory, and their brains were analyzed by IHC for vascularization and Aβ plaques. MSC-VEGF treatment favored the neovascularization and diminished senile plaques in hippocampal specific layers. Consequently, the treatment was able to provide behavioral benefits and reduce cognitive deficits by recovering the innate interest to novelty and counteracting memory deficits present in these AD transgenic animals. Therefore, this study has important therapeutic implications for the vascular damage in the neurodegeneration promoted by Alzheimer’s disease.

  17. Enhancement of Glutamate Release by l-Fucose Changes Effects of Glutamate Receptor Antagonists on Long-Term Potentiation in the Rat Hippocampus

    Science.gov (United States)

    Matthies, Henry; Schroeder, Helmut; Smalla, Karl-Heinz; Krug, Manfred

    2000-01-01

    In previous studies l-fucose has been shown to facilitate long-term memory formation and to enhance and prolong long-term potentiation (LTP). To search for possible presynaptic or postsynaptic mechanisms that are affected by l-fucose, we examined the effect of l-fucose on (1) inhibition of LTP induction via glutamate receptors by antagonists, (2) paired-pulse facilitation, and (3) presynaptic transmitter release. Coapplication of 0.2 mm l-fucose with the competitive N-methyl-d-aspartate (NMDA) receptor antagonist, d-2-amino-5-phosphonovalerate (AP5), or coapplication of 0.2 mml-fucose in the presence of an inhibitor for class I/II metabotropic glutamate receptors, (S)-α-methyl-4-carboxyphenylglycine (MCPG), reversed LTP blockade in the CA1-region of hippocampal slices. In contrast, l-fucose had no effect on the LTP blockade by the noncompetitive NMDA ion-channel blocker (5R,10S)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine hydrogen maleate (MK-801). Paired-pulse facilitation, which is a primarily presynaptic phenomenon of short-term plasticity, was decreased in the presence of 0.2 mm l-fucose. Furthermore, l-fucose enhanced the K+-stimulated release of [3H]-d-aspartate from preloaded hippocampal slices in a concentration-dependent manner. These observations demonstrate an influence of l-fucose on transmitter release that in turn can increase transmitter availability at postsynaptic glutamate receptors. This effect of l-fucose may contribute to the LTP facilitation seen in vitro and in vivo as well as to improvement in memory formation. PMID:10940323

  18. [Daily practice using the guidelines for prevention and treatment of osteoporosis. Effectiveness of exercise for preventing and treating osteoporosis].

    Science.gov (United States)

    Miyakoshi, Naohisa

    2008-08-01

    There is increasing evidence that exercise is an effective strategy for the prevention and treatment of osteoporosis. The randomized controlled trials and their meta-analyses to date, evaluating the effects of exercise on osteoporosis reveal that the exercise is effective in preserving bone mass, preventing fractures and falls, and improving quality of life in patients with osteoporosis. Emphasis is also given to the importance of the specific protocols of exercises needed to achieve positive effects safely, keeping in view the age and general physical condition of the person.

  19. Effect of Mobile Phone Microwaves on Fetal Period of Balb-C Mice in Histological Characteristics of Hippocampus and Learning Behaviors

    Directory of Open Access Journals (Sweden)

    Ali Moghimi

    2009-09-01

    Full Text Available Objective(sThe possible risks of radio-frequency electromagnetic fields (EMF for the living organisms and human body are a growing concern for our society. In this study, we examined the possibility of changes in working memory and hippocampal histological characteristics effects in mice brain following whole body exposure to microwave radiation.Materials and MethodsDuring gestation period, we exposed mice for 4 hr to Global system for mobile communications (GSM, Specific Absorption Rate (SAR of 200 mW/kg. Pregnant control mice were sham-exposed or free in a cage without further restraining. Three month after exposure animals were prepared for behavioral (Radial Arm Maze (RAM and Morris Water Maze (MWM and histological studies.ResultsThe results showed that microwave exposed mice were slower than sham, and control in finding the platform. Analyses of error rates in RAM and MWM performance revealed significant differences which emphasize the effect of acute exposure to pulsed microwaves in deficit of spatial reference memory in the mice. However in this study exposed group didn’t show any statistically significant loss of hippocampal CA1, CA3 neurons versus controls or sham. ConclusionWe conclude that there is evidence from the current study that exposure to MW radiation under parameters examined caused decrements in the ability of mice to learn the spatial memory task.

  20. Expression of somatostatin mRNA and peptide in rat hippocampus after cerebral ischemia

    DEFF Research Database (Denmark)

    Bering, Robert; Johansen, Flemming Fryd

    1993-01-01

    Somatostatin, ischemia, hippocampus, rat, in situ hybridisation, immunocytochemistry, neuropathology......Somatostatin, ischemia, hippocampus, rat, in situ hybridisation, immunocytochemistry, neuropathology...

  1. Preventive Effect of Salicylate and Pyridoxamine on Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Tarek Kamal Abouzed

    2016-01-01

    Full Text Available Objective. Diabetic nephropathy is a life-threatening complication in patients with long-standing diabetes. Hemodynamic, inflammatory, and metabolic factors are considered as developmental factors for diabetic nephropathy. In this study, we evaluated whether pharmacological interventions with salicylate, compared to pyridoxamine, could prevent diabetic nephropathy in mice. Methods. Male mice overexpressing inducible nitric oxide synthase in pancreatic β-cells were employed as a diabetic model. Salicylate (3 g/kg diet or pyridoxamine (1 g/L drinking water; ~200 mg/kg/day was given for 16 weeks to assess the development of diabetic nephropathy. Treatment with long-acting insulin (Levemir 2 units/kg twice a day was used as a control. Results. Although higher blood glucose levels were not significantly affected by pyridoxamine, early to late stage indices of nephropathy were attenuated, including kidney enlargement, albuminuria, and increased serum creatinine, glomerulosclerosis, and inflammatory and profibrotic gene expressions. Salicylate showed beneficial effects on diabetic nephropathy similar to those of pyridoxamine, which include lowering blood glucose levels and inhibiting macrophage infiltration into the kidneys. Attenuation of macrophage infiltration into the kidneys and upregulation of antiglycating enzyme glyoxalase 1 gene expression were found only in the salicylate treatment group. Conclusions. Treatment with salicylate and pyridoxamine could prevent the development of diabetic nephropathy in mice and, therefore, would be a potentially useful therapeutic strategy against kidney problems in patients with diabetes.

  2. Is Case Management Effective for Long-Lasting Suicide Prevention?

    Science.gov (United States)

    Wang, Liang-Jen; Wu, Ya-Wen; Chen, Chih-Ken

    2015-01-01

    Case management services have been implemented in suicide prevention programs. To investigate whether case management is an effective strategy for reducing the risks of repeated suicide attempts and completed suicides in a city with high suicide rates in northern Taiwan. The Suicide Prevention Center of Keelung City (KSPC) was established in April 2005. Subjects included a consecutive sample of individuals (N = 2,496) registered in KSPC databases between January 1, 2006, and December 31, 2011, with at least one episode of nonfatal self-harm. Subjects were tracked for the duration of the study. Of all the subjects, 1,013 (40.6%) received case management services; 416 (16.7%) had at least one other deliberate self-harm episode and 52 (2.1%) eventually died by suicide. No significant differences were found in the risks of repeated self-harm and completed suicides between suicide survivors who received case management and those who refused the services. However, a significant reduction in suicide rates was found after KSPC was established. Findings suggest that case management services might not reduce the risks of suicide repetition among suicide survivors during long-term follow-up. Future investigation is warranted to determine factors impacting the downward trend of suicide rates.

  3. Is systematic training in opioid overdose prevention effective?

    National Research Council Canada - National Science Library

    Albert Espelt; Marina Bosque-Prous; Cinta Folch; Ana Sarasa-Renedo; Xavier Majó; Jordi Casabona; M Teresa Brugal; REDAN Group

    2017-01-01

    The objectives were to analyze the knowledge about overdose prevention, the use of naloxone, and the number of fatal overdoses after the implementation of Systematic Training in Overdose Prevention (STOOP) program...

  4. Cost effectiveness of the MDOT preventive maintenance program.

    Science.gov (United States)

    2013-04-01

    The Michigan Department of Transportations (MDOT) pavement preservation program dates back to 1992. MDOTs pavement preservation strategy is primarily implemented through its capital preventive maintenance (CPM) program, in which preventive main...

  5. Inhibition of local estrogen synthesis in the hippocampus impairs hippocampal memory consolidation in ovariectomized female mice.

    Science.gov (United States)

    Tuscher, Jennifer J; Szinte, Julia S; Starrett, Joseph R; Krentzel, Amanda A; Fortress, Ashley M; Remage-Healey, Luke; Frick, Karyn M

    2016-07-01

    The potent estrogen 17β-Estradiol (E2) plays a critical role in mediating hippocampal function, yet the precise mechanisms through which E2 enhances hippocampal memory remain unclear. In young adult female rodents, the beneficial effects of E2 on memory are generally attributed to ovarian-synthesized E2. However, E2 is also synthesized in the adult brain in numerous species, where it regulates synaptic plasticity and is synthesized in response to experiences such as exposure to females or conspecific song. Although de novo E2 synthesis has been demonstrated in rodent hippocampal cultures, little is known about the functional role of local E2 synthesis in mediating hippocampal memory function. Therefore, the present study examined the role of hippocampal E2 synthesis in hippocampal memory consolidation. Using bilateral dorsal hippocampal infusions of the aromatase inhibitor letrozole, we first found that blockade of dorsal hippocampal E2 synthesis impaired hippocampal memory consolidation. We next found that elevated levels of E2 in the dorsal hippocampus observed 30min after object training were blocked by dorsal hippocampal infusion of letrozole, suggesting that behavioral experience increases acute and local E2 synthesis. Finally, aromatase inhibition did not prevent exogenous E2 from enhancing hippocampal memory consolidation, indicating that hippocampal E2 synthesis is not necessary for exogenous E2 to enhance hippocampal memory. Combined, these data are consistent with the hypothesis that hippocampally-synthesized E2 is necessary for hippocampus-dependent memory consolidation in rodents. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Connect: An Effective Community-Based Youth Suicide Prevention Program

    Science.gov (United States)

    Bean, Gretchen; Baber, Kristine M.

    2011-01-01

    Youth suicide prevention is an important public health issue. However, few prevention programs are theory driven or systematically evaluated. This study evaluated Connect, a community-based youth suicide prevention program. Analysis of pre and posttraining questionnaires from 648 adults and 204 high school students revealed significant changes in…

  7. The Open Method of Coordination - Effectively preventing welfare state retrenchment?

    Directory of Open Access Journals (Sweden)

    Milena Büchs

    2009-11-01

    Full Text Available This article re-examines the division between 'optimists' and 'pessimists' within the literature on the Open Method of Coordination’s (OMC effectiveness. Each of those 'camps' tends to focus on a different question. 'Optimists' are more concerned with the question of whether the OMC exerts an influence on the national level and through which mechanisms, whilst 'pessimists' concentrate on the question of whether the OMC can 'strengthen' EU social policy and therefore European welfare states. This article combines these two perspectives and argues that the OMC is indeed capable of influencing national policies through the dissemination of ideas and 'learning' as the 'optimists' stress. However, policy 'learning' at the member state level is shaped and constrained by a variety of internal and external pressures. Against the hopes of most of the OMC 'optimists', this makes the OMC largely ineffective in preventing welfare state retrenchment.

  8. Effect of indomethacin in preventing surgically induced miosis.

    Science.gov (United States)

    Keulen-de Vos, H C; van Rij, G; Renardel de Lavalette, J C; Jansen, J T

    1983-01-01

    A double-blind study was performed on 64 patients to assess the effect of preoperative indomethacin in comparison with a placebo in preventing surgically induced miosis during extracapsular cataract extraction. One drop of indomethacin or placebo was instilled at 7.00 p.m. and at 9.00 p.m. the night before surgery and 2 hours, 1 hour, and 15 minutes preoperatively. The pupil diameter was recorded at different stages of the operation. It was found that indomethacin as compared with the placebo significantly reduced the amount of pupil constriction during the operation, making the removal of lens material and the implantation of an intraocular lens easier. The indomethacin is thought to act by inhibiting prostaglandin synthesis caused by iris trauma during surgery. PMID:6336954

  9. Prevention of dental caries through the effective use of fluoride

    DEFF Research Database (Denmark)

    Petersen, Poul Erik

    2016-01-01

    Background: The World Health Organization (WHO) emphasizes that dental caries is a severe public health problem across the world. The current global and regional patterns of dental caries reflect distinct risk profiles of countries which relate to the structure of the society, living conditions......, lifestyles, and the existence of preventive oral health programmes. Research conducted in high income countries documents that systematic use of fluoride reduces the burden of dental caries; such research is scarce in low and middle income countries. Objectives: This article reviews the evidence on effective...... use of fluoride, highlights the public health approach to fluoridation, and clarifies how automatic fluoridation contributes to breaking social inequities in dental caries. Data collection: Scientific publications on fluoride administration stored in PubMed/Medline and caries data from the WHO...

  10. Prevention of dental caries through the effective use of fluoride

    DEFF Research Database (Denmark)

    Petersen, Poul Erik

    2016-01-01

    , lifestyles, and the existence of preventive oral health programmes. Research conducted in high income countries documents that systematic use of fluoride reduces the burden of dental caries; such research is scarce in low and middle income countries. Objectives: This article reviews the evidence on effective...... use of fluoride, highlights the public health approach to fluoridation, and clarifies how automatic fluoridation contributes to breaking social inequities in dental caries. Data collection: Scientific publications on fluoride administration stored in PubMed/Medline and caries data from the WHO...... databank. Outcome: Dental caries identified from national surveys or country relevant data; extraction of scientific reports is based on their public health relevance. Conclusions: The article outlines the history of fluoridation programmes and describes the sound evidence on automatic fluoridation through...

  11. Behavioural Effects of Adult Vitamin D Deficiency in BALB/c Mice Are not Associated with Proliferation or Survival of Neurons in the Adult Hippocampus.

    Directory of Open Access Journals (Sweden)

    Natalie J Groves

    Full Text Available Epidemiological studies have shown that up to one third of adults have insufficient levels of vitamin D and there is an association between low vitamin D concentrations and adverse brain outcomes, such as depression. Vitamin D has been shown to be involved in processes associated with neurogenesis during development. Therefore, the aim of this study was to test the hypothesis that adult vitamin D (AVD deficiency in BALB/c mice was associated with (a adult hippocampal neurogenesis at baseline, b following 6 weeks of voluntary wheel running and (c a depressive-like phenotype on the forced swim test (FST, which may be linked to alterations in hippocampal neurogenesis. We assessed proliferation and survival of adult born hippocampal neurons by counting the number of cells positive for Ki67 and doublecortin (DCX, and incorporation of 5-Bromo-2'-Deoxyuridine (BrdU within newly born mature neurons using immunohistochemistry. There were no significant effects of diet on number of Ki67+, DCX+ or BrdU+ cells in the dentate gyrus. All mice showed significantly increased number of Ki67+ cells and BrdU incorporation, and decreased immobility time in the FST, after voluntary wheel running. A significant correlation was found in control mice between immobility time in the FST and level of hippocampal neurogenesis, however, no such correlation was found for AVD-deficient mice. We conclude that AVD deficiency was not associated with impaired proliferation or survival of adult born neurons in BALB/c mice and that the impact on rodent behaviour may not be due to altered neurogenesis per se, but to altered function of new hippocampal neurons or processes independent of adult neurogenesis.

  12. Restorative effects of curcumin on sleep-deprivation induced memory impairments and structural changes of the hippocampus in a rat model.

    Science.gov (United States)

    Noorafshan, Ali; Karimi, Fatemeh; Kamali, Ali-Mohammad; Karbalay-Doust, Saied; Nami, Mohammad

    2017-11-15

    The present study examined the consequences of rapid eye-movement sleep-deprivation (REM-SD) with or without curcumin treatment. The outcome measures comprised quantitative features in the three-dimensional reconstruction (3DR) CA1 and dentate gyrus in experimental and control animals using stereological procedures. Male rats were arbitrarily assigned to nine groups based on the intervention and treatment administered including: 1-cage control+distilled water, 2-cage control+curcumin (100mg/kg/day), 3-cage control+olive oil, 4-REM-SD+distilled water, 5-REM-SD+curcumin, 6-REM-SD+olive oil, 7-grid-floor control+distilled water, 8-grid-floor control+curcumin, and 9-grid-floor control+olive oil. Animals in the latter three groups were placed on wire-mesh grids in the sleep-deprivation box. REM-SD was induced by an apparatus comprising a water tank and multiple platforms. After a period of 21days, rats were submitted to the novel object-recognition task. Later, their brains were excised and evaluated using stereological methods. Our results indicated a respective 29% and 31% reduction in the total volume of CA1, and dentate gyrus in REM-SD+distilled water group as compared to the grid-floor control+distilled water group (psleep-deprived group were found to be reduced by 48% and 25%, respectively. The REM-SD+distilled water group also exhibited impaired object recognition memory and deformed three-dimensional reconstructions of these regions. The volume, cell number, reconstruction, object recognition time, and body weight were however recovered in the REM-SD+curcumin compared to the REM-SD+distilled water group. This suggests the potential neuro-restorative effects of curcumin in our model. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Dose-dependent effects of morphine exposure on mRNA and microRNA (miR expression in hippocampus of stressed neonatal mice.

    Directory of Open Access Journals (Sweden)

    Ryan M McAdams

    Full Text Available Morphine is used to sedate critically ill infants to treat painful or stressful conditions associated with intensive care. Whether neonatal morphine exposure affects microRNA (miR expression and thereby alters mRNA regulation is unknown. We tested the hypothesis that repeated morphine treatment in stress-exposed neonatal mice alters hippocampal mRNA and miR expression. C57BL/6 male mice were treated from postnatal day (P 5 to P9 with morphine sulfate at 2 or 5 mg/kg ip twice daily and then exposed to stress consisting of hypoxia (100% N2 1 min and 100% O2 5 min followed by 2h maternal separation. Control mice were untreated and dam-reared. mRNA and miR expression profiling was performed on hippocampal tissues at P9. Overall, 2 and 5 mg/kg morphine treatment altered expression of a total of 150 transcripts (>1.5 fold change, P<0.05 from which 100 unique mRNAs were recognized (21 genes were up- and 79 genes were down-regulated, and 5 mg/kg morphine affected 63 mRNAs exclusively. The most upregulated mRNAs were fidgetin, arginine vasopressin, and resistin-like alpha, and the most down-regulated were defensin beta 11, aquaporin 1, calmodulin-like 4, chloride intracellular channel 6, and claudin 2. Gene Set Enrichment Analysis revealed that morphine treatment affected pathways related to cell cycle, membrane function, signaling, metabolism, cell death, transcriptional regulation, and immune response. Morphine decreased expression of miR-204-5p, miR-455-3p, miR-448-5p, and miR-574-3p. Nine morphine-responsive mRNAs that are involved in neurodevelopment, neurotransmission, and inflammation are predicted targets of the aforementioned differentially expressed miRs. These data establish that morphine produces dose-dependent changes in both hippocampal mRNA and miR expression in stressed neonatal mice. If permanent, morphine-mediated neuroepigenetic effects may affect long-term hippocampal function, and this provides a mechanism for the neonatal morphine

  14. [Effects of electroacupuncture at different acupoints on learning and memory ability and PSD-95 protein expression on hippocampus CA1 in rats with autism].

    Science.gov (United States)

    Zhang, Xue-Jun; Wu, Qiang

    2013-07-01

    To explore the effect mechanism of electroacupuncture (EA) at Changqiang (GV 1) or Baihui (GV 20) on autism based on molecular biology. The autism model was established by intraperitoneal injection of sodium valproate (VPA) in Wistar pregnant rats. Forty young rats with autism were selected and randomly divided into a model group, a non-acupoint group, an electroacupuncture at "Changqiang" (GV 1) (EAGV 1 for short) group and an electroacupuncture at "Baihui" (GV 20) (EAGV 20 for short) group. Another 10 normal young rats were selected as a blank group. In the EAGV 1 group, acupuncture was applied at Houhai [as Changqiang (GV 1)], then EA apparatus was connected with continuous wave, 2 Hz, 20 min, once a day for consecutive 20 days. The same EA manipulation as EAGV 1 group was used in the EAGV 20 group where "Baihui" (GV 20) was selected and non-acupoint group where non-acupoint in the right rib was selected. Blank group and model group were reared under the same conditions without any intervention. The escape latency and the ratio of swimming distance in platform quadrant to total swimming distance in each group were observed by using Morris water maze, and the PSD-95 protein expression in hippocampal CA 1 was measured by immunohistochemical techniques. Compared with the blank group, the escape latency in the model group and the non-acupoint group lengthened (both P swimming distance in platform quadrant to total swimming distance was decreased (both P swimming distance in platform quadrant to total swimming distance was increased, the PSD-95 protein expression was increased (both P swimming distance in platform quadrant to total swimming distance and the PSD-95 protein expression had no significant difference between EAGV 1 group and EAGV 20 group (P > 0.05). Electroacupuncture at Changqiang (GV 1) or Baihui (GV 20) can respectively improve learning and memory ability of rats with autism, which has no significant difference and the mechanism of action may be

  15. Effects of ischemic preconditioning on VEGF and pFlk-1 immunoreactivities in the gerbil ischemic hippocampus after transient cerebral ischemia.

    Science.gov (United States)

    Park, Yoo Seok; Cho, Jun Hwi; Kim, In Hye; Cho, Geum-Sil; Cho, Jeong-Hwi; Park, Joon Ha; Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Shin, Myoung Cheol; Tae, Hyun-Jin; Cho, Young Shin; Lee, Yun Lyul; Kim, Young-Myeong; Won, Moo-Ho; Lee, Jae-Chul

    2014-12-15

    Ischemia preconditioning (IPC) displays an important adaptation of the CNS to sub-lethal ischemia. In the present study, we examined the effect of IPC on immunoreactivities of VEGF-, and phospho-Flk-1 (pFlk-1) following transient cerebral ischemia in gerbils. The animals were randomly assigned to four groups (sham-operated-group, ischemia-operated-group, IPC plus (+) sham-operated-group, and IPC+ischemia-operated-group). IPC was induced by subjecting gerbils to 2 min of ischemia followed by 1 day of recovery. In the ischemia-operated-group, a significant loss of neurons was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) alone 5 days after ischemia-reperfusion, however, in all the IPC+ischemia-operated-groups, pyramidal neurons in the SP were well protected. In immunohistochemical study, VEGF immunoreactivity in the ischemia-operated-group was increased in the SP at 1 day post-ischemia and decreased with time. Five days after ischemia-reperfusion, strong VEGF immunoreactivity was found in non-pyramidal cells, which were identified as pericytes, in the stratum oriens (SO) and radiatum (SR). In the IPC+sham-operated- and IPC+ischemia-operated-groups, VEGF immunoreactivity was significantly increased in the SP. pFlk-1 immunoreactivity in the sham-operated- and ischemia-operated-groups was hardly found in the SP, and, from 2 days post-ischemia, pFlk-1 immunoreactivity was strongly increased in non-pyramidal cells, which were identified as pericytes. In the IPC+sham-operated-group, pFlk-1 immunoreactivity was significantly increased in both pyramidal and non-pyramidal cells; in the IPC+ischemia-operated-groups, the similar pattern of VEGF immunoreactivity was found in the ischemic CA1, although the VEGF immunoreactivity was strong in non-pyramidal cells at 5 days post-ischemia. In brief, our findings show that IPC dramatically augmented the induction of VEGF and pFlk-1 immunoreactivity in the pyramidal cells of the CA1 after ischemia

  16. Sleep deprivation impairs hippocampus-mediated contextual learning but not amygdala-mediated cued learning in rats.

    Science.gov (United States)

    Ruskin, David N; Liu, Caiqin; Dunn, Kelly E; Bazan, Nicolas G; LaHoste, Gerald J

    2004-06-01

    Prolonged sleep deprivation results in cognitive deficits. In rats, for example, sleep deprivation impairs spatial learning and hippocampal long-term potentiation. We tested the effects of sleep deprivation on learning in a Pavlovian fear conditioning paradigm, choosing a sleep deprivation paradigm in which REM sleep was completely prevented and non-REM sleep was strongly decreased. During conditioning, rats were given footshocks, either alone or paired with a tone, and tested 24 h later for freezing responses to the conditioning context, and to the tone in a novel environment. Whereas control animals had robust contextual learning in both background and foreground contextual conditioning paradigms, 72 h of sleep deprivation before conditioning dramatically impaired both types of contextual learning (by more than 50%) without affecting cued learning. Increasing the number of footshocks did not overcome the sleep deprivation-induced deficit. The results provide behavioural evidence that REM/non-REM sleep deprivation has neuroanatomically selective actions, differentially interfering with the neural systems underlying contextual learning (i.e. the hippocampus) and cued learning (i.e. the amygdala), and support the involvement of the hippocampus in both foreground and background contextual conditioning.

  17. Dendritic inhibition in the hippocampus supports fear learning.

    Science.gov (United States)

    Lovett-Barron, Matthew; Kaifosh, Patrick; Kheirbek, Mazen A; Danielson, Nathan; Zaremba, Jeffrey D; Reardon, Thomas R; Turi, Gergely F; Hen, René; Zemelman, Boris V; Losonczy, Attila

    2014-02-21

    Fear memories guide adaptive behavior in contexts associated with aversive events. The hippocampus forms a neural representation of the context that predicts aversive events. Representations of context incorporate multisensory features of the environment, but must somehow exclude sensory features of the aversive event itself. We investigated this selectivity using cell type-specific imaging and inactivation in hippocampal area CA1 of behaving mice. Aversive stimuli activated CA1 dendrite-targeting interneurons via cholinergic input, leading to inhibition of pyramidal cell distal dendrites receiving aversive sensory excitation from the entorhinal cortex. Inactivating dendrite-targeting interneurons during aversive stimuli increased CA1 pyramidal cell population responses and prevented fear learning. We propose subcortical activation of dendritic inhibition as a mechanism for exclusion of aversive stimuli from hippocampal contextual representations during fear learning.

  18. Stress, the hippocampus, and epilepsy

    NARCIS (Netherlands)

    Joëls, M.

    2009-01-01

    Stress is among the most frequently self-reported precipitants of seizures in patients with epilepsy. This review considers how important stress mediators like corticotropin-releasing hormone, corticosteroids, and neurosteroids could contribute to this phenomenon. Cellular effects of stress

  19. Intracranial EEG correlates of implicit relational inference within the hippocampus.

    Science.gov (United States)

    Reber, T P; Do Lam, A T A; Axmacher, N; Elger, C E; Helmstaedter, C; Henke, K; Fell, J

    2016-01-01

    Drawing inferences from past experiences enables adaptive behavior in future situations. Inference has been shown to depend on hippocampal processes. Usually, inference is considered a deliberate and effortful mental act which happens during retrieval, and requires the focus of our awareness. Recent fMRI studies hint at the possibility that some forms of hippocampus-dependent inference can also occur during encoding and possibly also outside of awareness. Here, we sought to further explore the feasibility of hippocampal implicit inference, and specifically address the temporal evolution of implicit inference using intracranial EEG. Presurgical epilepsy patients with hippocampal depth electrodes viewed a sequence of word pairs, and judged the semantic fit between two words in each pair. Some of the word pairs entailed a common word (e.g., "winter-red," "red-cat") such that an indirect relation was established in following word pairs (e.g., "winter-cat"). The behavioral results suggested that drawing inference implicitly from past experience is feasible because indirect relations seemed to foster "fit" judgments while the absence of indirect relations fostered "do not fit" judgments, even though the participants were unaware of the indirect relations. A event-related potential (ERP) difference emerging 400 ms post-stimulus was evident in the hippocampus during encoding, suggesting that indirect relations were already established automatically during encoding of the overlapping word pairs. Further ERP differences emerged later post-stimulus (1,500 ms), were modulated by the participants' responses and were evident during encoding and test. Furthermore, response-locked ERP effects were evident at test. These ERP effects could hence be a correlate of the interaction of implicit memory with decision-making. Together, the data map out a time-course in which the hippocampus automatically integrates memories from discrete but related episodes to implicitly influence future

  20. Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

    Science.gov (United States)

    Galinato, Melissa H.; Orio, Laura; Mandyam, Chitra D.

    2014-01-01

    Methamphetamine exposure reduces hippocampal long-term potentiation (LTP) and neurogenesis and these alterations partially contribute to hippocampal maladaptive plasticity. The potential mechanisms underlying methamphetamine-induced maladaptive plasticity were identified in the present study. Expression of brain-derived neurotrophic factor (BDNF; a regulator of LTP and neurogenesis), and its receptor tropomyosin-related kinase B (TrkB) were studied in the dorsal and ventral hippocampal tissue lysates in rats that intravenously self-administered methamphetamine in a limited access (1 h/day) or extended access (6 h/day) paradigm for 17 days post baseline sessions. Extended access methamphetamine enhanced expression of BDNF with significant effects observed in the dorsal and ventral hippocampus. Methamphetamine-induced enhancements in BDNF expression were not associated with TrkB receptor activation as indicated by phospho (p)-TrkB-706 levels. Conversely, methamphetamine produced hypophosphorylation of NMDA receptor subunit 2B (GluN2B) at Tyr-1472 in the ventral hippocampus, indicating reduced receptor activation. In addition, methamphetamine enhanced expression of anti-apoptotic protein Bcl-2 and reduced pro-apoptotic protein Bax levels in the ventral hippocampus, suggesting a mechanism for reducing cell death. Analysis of Akt, a pro-survival kinase that suppresses apoptotic pathways and pAkt at Ser-473 demonstrated that extended access methamphetamine reduces Akt expression in the ventral hippocampus. These data reveal that alterations in Bcl-2 and Bax levels by methamphetamine were not associated with enhanced Akt expression. Given that hippocampal function and neurogenesis vary in a subregion-specific fashion, where dorsal hippocampus regulates spatial processing and has higher levels of neurogenesis, whereas ventral hippocampus regulates anxiety-related behaviors, these data suggest that methamphetamine self-administration initiates distinct allostatic changes in

  1. Effects of the Strategic Prevention Framework State Incentives Grant (SPF SIG) on state prevention infrastructure in 26 states.

    Science.gov (United States)

    Orwin, Robert G; Stein-Seroussi, Alan; Edwards, Jessica M; Landy, Ann L; Flewelling, Robert L

    2014-06-01

    The Strategic Prevention Framework State Incentive Grant (SPF SIG) program is a national public health initiative sponsored by the U.S. Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Prevention to prevent substance abuse and its consequences. State grantees used a data-driven planning model to allocate resources to 450 communities, which in turn launched over 2,200 intervention strategies to target prevention priorities in their respective populations. An additional goal was to build prevention capacity and infrastructure at the state and community levels. This paper addresses whether the state infrastructure goal was achieved, and what contextual and implementation factors were associated with success. The findings are consistent with claims that, overall, the SPF SIG program met its goal of increasing prevention capacity and infrastructure across multiple infrastructure domains, though the mediating effects of implementation were evident only in the evaluation/monitoring domain. The results also show that an initiative like the SPF SIG, which could easily have been compartmentalized within the states, has the potential to permeate more broadly throughout state prevention systems.

  2. Effects of a Cancer Prevention Advertisement on Beliefs and Knowledge about Cancer Prevention.

    Science.gov (United States)

    Kye, Su Yeon; Yoo, Jisu; Lee, Min Hee; Jun, Jae Kwan

    2015-01-01

    Outcome-expectation beliefs and knowledge may ultimately influence behavior for cancer prevention. The aims of this study were to measure changes in knowledge and beliefs about cancer prevention before and after viewing a television advertisement and identify the factors affecting receptivity to its messages. A one-group pretest-posttest design was used in this study of 1,000 individuals aged 20 to 65 years who were recruited online in November 2014. The outcome variables included cancer prevention beliefs based on the Health Belief Model (five items) and knowledge about risk factors for cancer (seven items). Perceived susceptibility, perceived benefits, and self-efficacy increased significantly and their perceived severity and perceived barriers decreased significantly, after participants viewed the television advertisement. Correct responses to questions about risk factors also increased significantly, except for smoking. The main factors affecting changes in the outcome variables were age, interest in cancer prevention, social network, satisfaction with the ad, and pretest scores. Television advertisements with positive frameworks can be an efficient channel of improving beliefs and knowledge about cancer prevention in a short period. The continuous development of intervention materials that consider the demographics, needs, and satisfaction of the target group will be necessary for future studies.

  3. Intrinsic connectivity between the hippocampus, nucleus accumbens, and ventral tegmental area in humans.

    Science.gov (United States)

    Kahn, I; Shohamy, D

    2013-03-01

    Recent studies suggest that memory formation in the hippocampus is modulated by the motivational significance of events, allowing past experience to adaptively guide behavior. The effects of motivation on memory are thought to depend on interactions between the hippocampus, the ventral tegmental area (VTA), and the nucleus accumbens (NAcc). Indeed, animal studies reveal anatomical pathways for circuit-level interaction between these regions. However, a homologue circuit connectivity in humans remains to be shown. We characterized this circuitry in humans by exploiting spontaneous low-frequency modulations in the fMRI signal (termed resting-state functional connectivity), which are thought to reflect functionally related regions and their organization into functional networks in the brain. We examined connectivity in this network across two datasets (hi-resolution, n = 100; standard resolution, n = 894). Results reveal convergent connectivity between the hippocampus, and both the NAcc and the VTA centered on ventral regions in the body of the hippocampus. Additionally, we found individual differences in the strength of connectivity within this network. Together, these results provide a novel task-independent characterization of circuitry underlying interactions between the hippocampus, NAcc, and VTA and provide a framework with which to understand how connectivity might reflect and constrain the effects of motivation on memory. Copyright © 2012 Wiley Periodicals, Inc.

  4. Memory, scene construction, and the human hippocampus.

    Science.gov (United States)

    Kim, Soyun; Dede, Adam J O; Hopkins, Ramona O; Squire, Larry R

    2015-04-14

    We evaluated two different perspectives about the function of the human hippocampus--one that emphasizes the importance of memory and another that emphasizes the importance of spatial processing and scene construction. We gave tests of boundary extension, scene construction, and memory to patients with lesions limited to the hippocampus or large lesions of the medial temporal lobe. The patients were intact on all of the spatial tasks and impaired on all of the memory tasks. We discuss earlier studies that associated performance on these spatial tasks to hippocampal function. Our results demonstrate the importance of medial temporal lobe structures for memory and raise doubts about the idea that these structures have a prominent role in spatial cognition.

  5. Functional neurogenesis in the adult hippocampus

    Science.gov (United States)

    van Praag, Henriette; Schinder, Alejandro F.; Christie, Brian R.; Toni, Nicolas; Palmer, Theo D.; Gage, Fred H.

    2002-02-01

    There is extensive evidence indicating that new neurons are generated in the dentate gyrus of the adult mammalian hippocampus, a region of the brain that is important for learning and memory. However, it is not known whether these new neurons become functional, as the methods used to study adult neurogenesis are limited to fixed tissue. We use here a retroviral vector expressing green fluorescent protein that only labels dividing cells, and that can be visualized in live hippocampal slices. We report that newly generated cells in the adult mouse hippocampus have neuronal morphology and can display passive membrane properties, action potentials and functional synaptic inputs similar to those found in mature dentate granule cells. Our findings demonstrate that newly generated cells mature into functional neurons in the adult mammalian brain.

  6. Preventive effect of pidotimod on reactivated toxoplasmosis in mice.

    Science.gov (United States)

    Huo, Xing-Xing; Wang, Lin; Chen, Zhao-Wu; Chen, He; Xu, Xiu-Cai; Zhang, Ai-Mei; Song, Xiao-Rong; Luo, Qing-Li; Xu, Yuan-Hong; Fu, Yu; Wang, Hua; Du, Jian; Cai, Yi-Hong; Lun, Zhao-Rong; Lu, Fang-Li; Wang, Yong; Shen, Ji-Long

    2013-08-01

    As one of food-borne parasitic diseases, toxoplasmosis entails the risk of developing reactivation in immunocompromised patients. The synthetic dipeptide pidotimod is a potent immunostimulating agent that improves the immunodefenses in immunodepression. To investigate the efficacy of pidotimod as a preventive treatment, we used a murine model of reactivated toxoplasmosis with cyclophosphamide (CY)-induced immunosuppression. Pidotimod administration significantly restored the body weight and spleen organ index, increased survival time (from 70 to 90%), and decreased the parasitemia (from 80 to 35%) of CY-induced mice with reactivated toxoplasmosis. Cytokine profiles and CD4(+) T cells subpopulation analyses by Cytometric Bead Array and flow cytometry demonstrated that pidotimod treatment resulted in a significant upregulation of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-2) and Th1 cells (from 3.73 ± 0.39 to 5.88 ± 0.46%) after CY induction in infected mice. Additionally, histological findings and parasite DNA quantification revealed that mice administered with pidotimod had a remarkable reduction of parasite burden (two-log) and amelioration of histopathology in the brains. The in vitro studies showed that pidotimod significantly restored concanavalin A-induced splenocyte proliferation and pro-inflammatory cytokines in the supernatants of splenocyte culture. It could be concluded that the administration of pidotimod in immunocompromised mice significantly increases the Th1-biased immune response, prolongs survival time, and ameliorates the load of parasites in the blood. This is the first report of the preventive effect of pidotimod on reactivated toxoplasmosis.

  7. Caries-preventive Effect of Supervised Toothbrushing and Sealants.

    Science.gov (United States)

    Hilgert, L A; Leal, S C; Mulder, J; Creugers, N H J; Frencken, J E

    2015-09-01

    To investigate the effectiveness of 3 caries-preventive measures on high- and low-caries risk occlusal surfaces of first permanent molars over 3 y. This cluster-randomized controlled clinical trial covered 242 schoolchildren, 6 to 7 y old, from low socioeconomic areas. At baseline, caries risk was assessed at the tooth surface level, through a combination of ICDAS II (International Caries Detection and Assessment System) and fissure depth codes. High-caries risk occlusal surfaces were treated according to daily supervised toothbrushing (STB) at school and 2 sealants: composite resin (CR) and atraumatic restorative treatment-high-viscosity glass-ionomer cement (ART-GIC). Low-caries risk occlusal surfaces received STB or no intervention. Evaluations were performed after 0.5, 1, 2, and 3 y. A cavitated dentine carious lesion was considered a failure. Data were analyzed according to the proportional hazard rate regression model with frailty correction, Wald test, analysis of variance, and t test, according to the jackknife procedure for calculating standard errors. The cumulative survival rates of cavitated dentine carious lesion-free, high-caries risk occlusal surfaces were 95.6%, 91.4%, and 90.2% for STB, CR, and ART-GIC, respectively, over 3 y, which were not statistically significantly different. For low-caries risk occlusal surfaces, no statistically significant difference was observed between the cumulative survival rate of the STB group (94.8%) and the no-intervention group (92.1%) over 3 y. There was neither a difference among STB, CR, and ART-GIC on school premises in preventing cavitated dentine carious lesions in high-caries risk occlusal surfaces of first permanent molars nor a difference between STB and no intervention for low-caries risk occlusal surfaces of first permanent molars over 3 y. © International & American Associations for Dental Research 2015.

  8. The effects of framed messages for engaging adolescents with online smoking prevention interventions

    National Research Council Canada - National Science Library

    Mays, Darren; Hawkins, Kirsten B; Bredfeldt, Christine; Wolf, Hilary; Tercyak, Kenneth P

    2017-01-01

    ...) may be effective for engaging adolescents with tobacco prevention resources. This novel approach could help to close a gap in tobacco prevention intervention delivery in the pediatric primary care setting...

  9. Evaluating the effects of a message on attitude and intention to eat raw meat: Salmonellosis prevention

    National Research Council Canada - National Science Library

    Trifiletti, Elena; Crovato, Stefania; Capozza, Dora; Visintin, Emilio Paolo; Ravarotto, Licia

    2012-01-01

    .... The prevention message proved to be very effective. First, it changed the attitude toward raw or rare meat, which after having read the prevention message was evaluated less positively and more negatively...

  10. Hippocampus and Remote Spatial Memory in Rats

    OpenAIRE

    Clark, Robert E.; Broadbent, Nicola J.; Squire, Larry R.

    2005-01-01

    Damage to the hippocampus typically produces temporally graded retrograde amnesia, whereby memories acquired recently are impaired more than memories acquired remotely. This phenomenon has been demonstrated repeatedly in a variety of species and tasks. It has also figured prominently in theoretical treatments of memory and hippocampal function. Yet temporally graded retrograde amnesia has not been demonstrated following hippocampal damage in spatial tasks like the water maze. We have assessed...

  11. Prevention of dental caries: A review of effective treatments.

    Science.gov (United States)

    Sicca, Claudio; Bobbio, Elena; Quartuccio, Natale; Nicolò, Giovanni; Cistaro, Angelina

    2016-12-01

    The objective of this study is to review medical and non medical treatments for prevention of caries. A comprehensive literature search of the most relevant and updated published studies from 01/01/2002 through December 2015 in PubMed/MEDLINE, Embase and Scopus databases regarding the efficacy of strategies and treatments aiming to prevent the development of caries was performed selecting papers on the basis of the Evidence-based Medicine Criteria. We identified thirty systematic reviews on prevention of caries. Analyzing the data the retrieved literature, performance of prevention treatments seems to be high. Prevention treatments may have a relevant impact on the avoiding the development of caries planning. Key words: Dental caries, prevention, fluoride.

  12. Preventive effects of an intergenerational program on age-related hippocampal atrophy in older adults: The REPRINTS study.

    Science.gov (United States)

    Sakurai, Ryota; Ishii, Kenji; Sakuma, Naoko; Yasunaga, Masashi; Suzuki, Hiroyuki; Murayama, Yoh; Nishi, Mariko; Uchida, Hayato; Shinkai, Shoji; Fujiwara, Yoshinori

    2017-08-31

    A growing body of literature indicates that social engagements, such as intergenerational programs, are effective strategies to improve a range of cognitive abilities. The present study examined whether the intergenerational program-REPRINTS-prevents age-related hippocampal atrophy. After comprehensive baseline assessment, participants were allowed to decide whether to participate in the REPRINTS intervention or in the control group, which required only completion of assessments. REPRINTS participants engaged in group activities that involved reading picture books to children at kindergarten and elementary schools, once every 1 to 2 weeks. A follow-up assessment was conducted after 6 years. Two MRI scans were performed, one immediately after baseline assessment and the other after 6 years. Volumes of the hippocampus, thalamus, and caudate nucleus were derived from automated segmentation. The analysis included 17 REPRINTS and 42 control-group participants. There was no significant difference in any variable of participants' characteristics at baseline between the REPRINTS and control groups. Hippocampal volume significantly declined in the control group but was maintained in the REPRINTS group. No significant differences between groups in thalamus or caudate nucleus volume were observed. Although cognitive function was unaffected by the program, greater decreases in hippocampal volume were significantly correlated with greater decreases in cognitive performance scores. Our results suggest that the REPRINTS intergenerational program has protective effects on age-related hippocampal atrophy in older adults. These changes precede improvements in cognitive performance, suggesting the validity of the concept of brain plasticity in later life following social engagement. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Effects of anthocyanins on the prevention and treatment of cancer.

    Science.gov (United States)

    Lin, Bo-Wen; Gong, Cheng-Chen; Song, Hai-Fei; Cui, Ying-Yu

    2017-06-01

    Anthocyanins are a class of water-soluble flavonoids, which show a range of pharmacological effects, such as prevention of cardiovascular disease, obesity control and antitumour activity. Their potential antitumour effects are reported to be based on a wide variety of biological activities including antioxidant; anti-inflammation; anti-mutagenesis; induction of differentiation; inhibiting proliferation by modulating signal transduction pathways, inducing cell cycle arrest and stimulating apoptosis or autophagy of cancer cells; anti-invasion; anti-metastasis; reversing drug resistance of cancer cells and increasing their sensitivity to chemotherapy. In this review, the latest progress on the anticancer activities of anthocyanins and the underlying molecular mechanisms is summarized using data from basic research in vitro and in vivo, from clinical trials and taking into account theory and practice. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2016 The British Pharmacological Society.

  14. Preventive and therapeutic effects of tranexamic acid on postpartum bleeding

    Directory of Open Access Journals (Sweden)

    Samaneh Solltani

    2014-12-01

    Full Text Available Postpartum hemorrhage is among the leading causes of maternal mortality throughout the world. Severe blood loss contributes to  the increased blood transfusion risk with its concerned inherent adverse events and therefore increased rate of emergency re-operative interventions such as arterial ligation or hysterectomy. It also can lead to protracted anemia, particularly in low or median income countries. Extended application of antifibrinolytic agents such as tranexamic acid has been customary for long years to stop or reduce blood loss in postpartum period. However, there are not enough reliable evidence to approve the real efficacy of these drugs. In this brief and summary review, we pointed to a few conducted studies. The PubMed was searched for keyword including postpartum hemorrhage, tranexamic acid, cesarean section, vaginal delivery, and blood loss prevention. The articles with language other than English were excluded from our review.  We concluded that more convincing information is needed to determine the precise effects of tranexamic acid, and its benefits against adverse effects.

  15. Effect of Education on Prevention of Domestic Violence against Women

    Directory of Open Access Journals (Sweden)

    Fatemeh Noughani

    2011-06-01

    Full Text Available "nObjective: Family violence, specifically domestic violence, has been identified by the medical community as a serious, no remitting epidemic with adverse health consequences. World Health Organization(WHO has stated that violence against women is a priority issue in the fields of health and human rights. A quasi experimental study were conducted in different faculties of Tehran University of Medical Sciences to determine the effect of teaching on prevention of domestic violence against female employees. "nMethods: Forty four women working in various faculties of Tehran University of Medical Sciences in 2004 were selected. A designed questionnaire was given to the participants to identify kinds, causes and consequences of domestic violence. Then an educational booklet was given to subjects. This booklet contained information about kinds, causes  and consequences of domestic violence and how to manage them. To compare the impact of teaching, the same questionnaires were distributed among the subjects after six months. The questionnaire was specifically tested for content validity. "nResults:The results indicated that the incidence rate of domestic violence pre test and post test education was 5.17%. "nConclusion: Our study showed that education had no effect on domestic violence. Solving problems relating to domestic violence due to cardinal roots in short time seems to be impossible and impracticable.

  16. Contributions of the hippocampus to feedback learning.

    Science.gov (United States)

    Dickerson, Kathryn C; Delgado, Mauricio R

    2015-12-01

    Humans learn about the world in a variety of manners, including by observation, by associating cues in the environment, and via feedback. Across species, two brain structures have been predominantly involved in these learning processes: the hippocampus--supporting learning via observation and paired association--and the striatum--critical for feedback learning. This simple dichotomy, however, has recently been challenged by reports of hippocampal engagement in feedback learning, although the role of the hippocampus is not fully understood. The purpose of this experiment was to characterize the hippocampal response during feedback learning by manipulating varying levels of memory interference. Consistent with prior reports, feedback learning recruited the striatum and midbrain. Notably, feedback learning also engaged the hippocampus. The level of activity in these regions was modulated by the degree of memory interference, such that the greatest activation occurred during the highest level of memory interference. Importantly, the accuracy of information learned via feedback correlated with hippocampal activation and was reduced by the presence of high memory interference. Taken together, these findings provide evidence of hippocampal involvement in feedback learning by demonstrating both its relevance for the accuracy of information learned via feedback and its susceptibility to interference.

  17. Deafferentation Enhances Neurogenesis in the Young and Middle Aged Hippocampus but not in the Aged Hippocampus

    Science.gov (United States)

    Shetty, Ashok K.; Hattiangady, Bharathi; Rao, Muddanna S.; Shuai, Bing

    2010-01-01

    Increased neurogenesis in the dentate gyrus (DG) after brain insults such as excitotoxic lesions, seizures or stroke is a well known phenomenon in the young hippocampus. This plasticity reflects an innate compensatory response of neural stem cells (NSCs) in the young hippocampus to preserve function or minimize damage after injury. However, injuries to the middle-aged and aged hippocampi elicit either no or dampened neurogenesis response, which could be due to an altered plasticity of NSCs and/or the hippocampus with age. We examined whether the plasticity of NSCs to increase neurogenesis in response to a milder injury such as partial deafferentation is preserved during aging. We quantified DG neurogenesis in the hippocampus of young, middle-aged and aged F344 rats after partial deafferentation. A partial deafferentation of the left hippocampus without any apparent cell loss was induced via administration of Kainic acid (0.5 μg in 1.0 μl) into the right lateral ventricle of the brain. In this model, degeneration of CA3 pyramidal neurons and dentate hilar neurons in the right hippocampus results in loss of commissural axons which leads to partial deafferentation of the dendrites of dentate granule cells and CA1-CA3 pyramidal neurons in the left hippocampus. Quantification of newly born cells that are added to the dentate granule cell layer at post-deafferentation days 4-15 using 5′-bromodeoxyuridine (BrdU) labeling revealed greatly increased addition of newly born cells (~3 fold increase) in the deafferented young and middle-aged hippocampi but not in the deafferented aged hippocampus. Measurement of newly born neurons using doublecortin (DCX) immunostaining also revealed similar findings. Analyses using BrdU-DCX dual immunofluorescence demonstrated no changes in neuronal fate-choice decision of newly born cells after deafferentation, in comparison to the age-matched naive hippocampus in all age groups. Thus, the plasticity of hippocampal NSCs to increase DG

  18. Ulinastatin suppresses endoplasmic reticulum stress and apoptosis in the hippocampus of rats with acute paraquat poisoning

    Directory of Open Access Journals (Sweden)

    Hai-feng Li

    2015-01-01

    Full Text Available Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline. Hematoxylin-eosin staining showed that most hippocampal cells were contracted and nucleoli had disappeared in the paraquat group. Fewer cells in the hippocampus were concentrated and nucleoli had disappeared in the ulinastatin group. Western blot assay showed that expressions of GRP78 and cleaved-caspase-3 were significantly lower in the ulinastatin group than in the paraquat group. Immunohistochemical findings showed that CHOP immunoreactivity was significantly lower in the ulinastatin group than in the paraquat group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining showed that the number of apoptotic cells was reduced in the paraquat and ulinastatin groups. These data confirmed that endoplasmic reticular stress can be induced by acute paraquat poisoning. Ulinastatin can effectively inhibit this stress as well as cell apoptosis, thereby exerting a neuroprotective effect.

  19. Pre-exposure prophylaxis for HIV-1 prevention does not diminish the pregnancy prevention effectiveness of hormonal contraception.

    Science.gov (United States)

    Murnane, Pamela M; Heffron, Renee; Ronald, Allan; Bukusi, Elizabeth A; Donnell, Deborah; Mugo, Nelly R; Were, Edwin; Mujugira, Andrew; Kiarie, James; Celum, Connie; Baeten, Jared M

    2014-07-31

    For women at risk of HIV-1, effective contraception and effective HIV-1 prevention are global priorities. In a clinical trial of pre-exposure prophylaxis (PrEP) for HIV-1 prevention in HIV-1-serodiscordant couples, we estimated the effectiveness of hormonal contraceptives (oral contraceptive pills, injectable depot medroxyprogesterone acetate, and hormonal implants) for pregnancy prevention relative to no contraception among 1785 HIV-1-uninfected women followed up to 36 months. We compared the effectiveness of each method among women assigned PrEP versus placebo. Contraception was not required for participation, but was offered on-site and was recorded monthly; incident pregnancy was determined by monthly urine testing. For women using no contraception, overall pregnancy incidence was 15.4% per year. Women reporting oral contraceptive use had comparable pregnancy incidence to women using no contraception, and this lack of contraceptive effectiveness was similar for those assigned PrEP and placebo (17.7 and 10.0% incidence per year, respectively; P-value for difference in effect by PrEP use = 0.24). Women reporting injectable contraception had reduced pregnancy incidence compared to those reporting no contraception, which did not differ by arm (PrEP 5.1%, placebo 5.3% per year; P-value for difference = 0.47). Contraceptive effectiveness was highest among women using implants (pregnancy incidence pregnancy prevention. As seen previously in similar populations, women reporting contraceptive pill use had little protection from pregnancy, possibly due to poor adherence. Injectable or implantable hormonal contraception and PrEP provide effective prevention for pregnancy and HIV-1.

  20. Apoptotic Process Induced by Oxaliplatin in Rat Hippocampus Causes Memory Impairment.

    Science.gov (United States)

    Bianchi, Enrica; Di Cesare Mannelli, Lorenzo; Micheli, Laura; Farzad, Mersedez; Aglianò, Margherita; Ghelardini, Carla

    2017-01-01

    Aspects of memory involved in cognitive mechanisms were investigated in rat after oxaliplatin (OX) chemotherapy using animal behavioural assessment of passive avoidance and social learning paradigms, which are both hippocampus-sensitive. Rodents, previously subjected to 2-week OX treatment, showed passive avoidance and social learning impairment and apoptotic processes in the hippocampus. Apoptosis rate significantly increased in cultured hippocampal cells exposed to OX at increasing doses, and this effect was dose-dependent. Ex vivo experiments showed that cell damage and apoptosis were blocked in the hippocampus from OX rats cotreated with copper sulphate (CS) which precludes OX transport inside the cell. In vivo, passive avoidance and social learning impairment could not be observed in OX rats co-administered with CS. Thus, a site of action of OX treatment on memory impairment appears to be located at the hippocampus. These findings strongly support that cellular damage induced by OX in rodent hippocampus underlies the weakening of some memory functions. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  1. Hippocampus and amygdala volumes in patients with borderline personality disorder with or without posttraumatic stress disorder

    Science.gov (United States)

    Schmahl, Christian; Berne, Kevin; Krause, Annegret; Kleindienst, Nikolaus; Valerius, Gabriele; Vermetten, Eric; Bohus, Martin

    2009-01-01

    Background Several studies have investigated volumetric brain changes in patients with posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD). Both groups exhibit volume reductions of the hippocampus and amygdala. Our aim was to investigate the influence of comorbid PTSD on hippocampus and amygdala volumes in patients with BPD. Methods We compared 2 groups of unmedicated female patients with BPD (10 with and 15 without comorbid PTSD) and 25 healthy female controls. We used T1- and T2-weighted magnetic resonance images for manual tracing and 3-dimensional reconstruction of the hippocampus and amygdala. Results Hippocampus volumes of patients with BPD and PTSD were smaller than those of healthy controls. However, there was no significant difference between patients with BPD but without PTSD and controls. Impulsiveness was positively correlated with hippocampus volumes in patients with BPD. Limitations Our study did not allow for disentangling the effects of PTSD and traumatization. Another limitation was the relatively small sample size. Conclusion Our findings highlight the importance of classifying subgroups of patients with BPD. Comorbid PTSD may be related to volumetric alterations in brain regions that are of central importance to our understanding of borderline psychopathology. PMID:19568480

  2. Rats use hippocampus to recognize positions of objects located in an inaccessible space.

    Science.gov (United States)

    Levcik, D; Nekovarova, T; Stuchlik, A; Klement, D

    2013-02-01

    Rat hippocampus plays a crucial role in many spatial tasks, including recognition of position of objects, which can be approached and explored. Whether hippocampus is also necessary for recognizing positions of objects located in an inaccessible part of the environment remains unclear. To address this question, we conditioned rats to press a lever when an object displayed on a distant computer screen was in a particular position ("reward position") and not to press the lever when the object was in other positions ("nonreward positions"). After the rats had reached an asymptotic performance, the role of the dorsal hippocampus was assessed by blocking its activity with muscimol. The rats without functional dorsal hippocampus did not discriminate the reward position from the nonreward positions. Then the same rats were trained to discriminate light and dark conditions. The hippocampal inactivation did not disrupt the ability to discriminate these two conditions. It indicated that the inactivation itself had no major effect on the operant behavior and its control by visual stimuli. We conclude that rats use dorsal hippocampus for recognizing positions of objects located in an inaccessible part of the environment. Copyright © 2012 Wiley Periodicals, Inc.

  3. Endogenous nociceptin/orphanin-FQ in the dorsal hippocampus facilitates despair-related behavior.

    Science.gov (United States)

    Goeldner, Celia; Reiss, David; Kieffer, Brigitte L; Ouagazzal, Abdel-Mouttalib

    2010-08-01

    Nociceptin/orphanin-FQ (N/OFQ) peptide and its receptor (NOP: N/OFQ opioid peptide receptor) are highly expressed in the hippocampus, but their functional role remains poorly understood. We recently showed that hippocampal N/OFQ inhibits learning and memory abilities in mice. Here, we investigated whether the endogenous peptide also regulated emotional responses at the level of the hippocampus. Bilateral infusions of the selective NOP receptor antagonist, UFP-101 (1-3 nmol/side), into the dorsal hippocampus produced antidepressant-like effects in the mouse forced swim and tail suspension tests comparable with those obtained with the prototypical antidepressant, fluoxetine (10-30 mg/kg, intraperitoneal). In the light-dark test, neither UFP-101 (1-3 nmol/side) nor N/OFQ peptide (1-3 nmol/side) modified anxiety measures when injected at behaviorally active doses in the dorsal hippocampus. These findings show a clear dissociation in the involvement of hippocampal N/OFQ system in anxiety- and despair-related behaviors. We conclude that the dorsal hippocampus is a brain region in which there is an important N/OFQ modulation of mnemonic processes and adaptive emotional responses associated to despair states. Copyright 2010 Wiley-Liss, Inc.

  4. Biopersistence of PEGylated Carbon Nanotubes Promotes a Delayed Antioxidant Response after Infusion into the Rat Hippocampus.

    Directory of Open Access Journals (Sweden)

    Lidiane Dal Bosco

    Full Text Available Carbon nanotubes are promising nanomaterials for the diagnosis and treatment of brain disorders. However, the ability of these nanomaterials to cross cell membranes and interact with neural cells brings the need for the assessment of their potential adverse effects on the nervous system. This study aimed to investigate the biopersistence of single-walled carbon nanotubes functionalized with polyethylene glycol (SWCNT-PEG directly infused into the rat hippocampus. Contextual fear conditioning, Y-maze and open field tasks were performed to evaluate the effects of SWCNT-PEG on memory and locomotor activity. The effects of SWCNT-PEG on oxidative stress and morphology of the hippocampus were assessed 1 and 7 days after infusion of the dispersions at 0.5, 1.0 and 2.1 mg/mL. Raman analysis of the hippocampal homogenates indicates the biopersistence of SWCNT-PEG in the hippocampus 7 days post-injection. The infusion of the dispersions had no effect on the acquisition or persistence of the contextual fear memory; likewise, the spatial recognition memory and locomotor activity were not affected by SWCNT-PEG. Histological examination revealed no remarkable morphological alterations after nanomaterial exposure. One day after the infusion, SWCNT-PEG dispersions at 0.5 and 1.0 mg/mL were able to decrease total antioxidant capacity without modifying the levels of reactive oxygen species or lipid hydroperoxides in the hippocampus. Moreover, SWCNT-PEG dispersions at all concentrations induced antioxidant defenses and reduced reactive oxygen species production in the hippocampus at 7 days post-injection. In this work, we found a time-dependent change in antioxidant defenses after the exposure to SWCNT-PEG. We hypothesized that the persistence of the nanomaterial in the tissue can induce an antioxidant response that might have provided resistance to an initial insult. Such antioxidant delayed response may constitute an adaptive response to the biopersistence of

  5. Effect of "phase change" complex on postoperative adhesion prevention.

    Science.gov (United States)

    Li, Xiao-Dong; Xia, Dong-Lin; Shen, Ling-Ling; He, Hong; Chen, Chao; Wang, Yu-Fei; Chen, Yan-Pei; Guo, Ling-Yan; Gu, Hai-Ying

    2016-05-01

    Postsurgical peritoneal adhesion is a major clinical problem. Numerous anti-adhesion products have been studied, but none could be easily used to provide a physical barrier. In this study, we developed a "phase change" anti-adhesion barrier for reducing peritoneal adhesion by cross-linked copolymerization of O-carboxymethyl chitosan (CMC) and CaCl2 and addition of cyclosporin A (CsA). The CMC-CaCl2-CsA compound was characterized by equilibrium swelling rate, weight loss, releasing effect, and coagulation test, and its biosafety was characterized by acute oral toxicity, hemolysis, and cytotoxicity. Intestinal adhesion model was applied on 64 Sprague-Dawley rats, which received CMC, CMC-CaCl2, or CMC-CaCl2-CsA treatment. At postoperative days 7 and 14, the rats were euthanized, and adhesions were graded by an investigator blinded to the treatment groups, using a predetermined adhesion scoring system. The cecum and adhesion tissue were stained with hematoxylin and eosin and antibodies for matrix metalloproteinase-9 and TIMP-1 for further histopathologic examination. The phase change anti-adhesive material exhibited effective blood clotting and were nontoxic in clotting experiments and acute toxicity test. The degradation rate could be adjusted using phosphate-buffered solution with varying pH. Adhesions were significantly reduced in the CMC-CaCl2-CsA treatment group compared with the control group (P treatment group at 7 days after surgery. "Phase-change" adhesive can undergo changes after application, and it inhibits the formation of abdominal adhesions after surgery. The material is convenient for using by surgeons and provides an effective tool for intestinal adhesion prevention. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Effectiveness of a Social Change Approach to Sexual Assault Prevention

    Science.gov (United States)

    Edwards, Keith E.

    2009-01-01

    The author examined the impact on resident assistants of a social change approach to sexual assault prevention. The interactive multi-media program focused on engaging men on sexual assault prevention, accurately defining rape for college men and women, identifying aspects of the rape culture in society and on-campus, and empowering college…

  7. The effectiveness of exercise interventions to prevent sports injuries

    DEFF Research Database (Denmark)

    Lauersen, Jeppe Bo; Bertelsen, Ditte Marie; Andersen, Lars Bo

    2014-01-01

    Physical activity is important in both prevention and treatment of many common diseases, but sports injuries can pose serious problems.......Physical activity is important in both prevention and treatment of many common diseases, but sports injuries can pose serious problems....

  8. High Plasticity of New Granule Cells in the Aging Hippocampus

    Directory of Open Access Journals (Sweden)

    Mariela F. Trinchero

    2017-10-01

    Full Text Available Summary: During aging, the brain undergoes changes that impair cognitive capacity and circuit plasticity, including a marked decrease in production of adult-born hippocampal neurons. It is unclear whether development and integration of those new neurons are also affected by age. Here, we show that adult-born granule cells (GCs in aging mice are scarce and exhibit slow development, but they display a remarkable potential for structural plasticity. Retrovirally labeled 3-week-old GCs in middle-aged mice were small, underdeveloped, and disconnected. Neuronal development and integration were accelerated by voluntary exercise or environmental enrichment. Similar effects were observed via knockdown of Lrig1, an endogenous negative modulator of neurotrophin receptors. Consistently, blocking neurotrophin signaling by Lrig1 overexpression abolished the positive effects of exercise. These results demonstrate an unparalleled degree of plasticity in the aging brain mediated by neurotrophins, whereby new GCs remain immature until becoming rapidly recruited to the network by activity. : Trinchero et al. show that development of new granule cells born in the adult hippocampus is strongly influenced by age. In the aging hippocampus, new neurons remain immature for prolonged intervals, yet voluntary exercise triggers their rapid growth and functional synaptogenesis. This extensive structural remodeling is mediated by neurotrophins. Keywords: adult neurogenesis, dentate gyrus, functional integration, neurotrophins, synaptogenesis, exercise

  9. Proteomic Analysis of Rat Hippocampus under Simulated Microgravity

    Science.gov (United States)

    Wang, Yun; Li, Yujuan; Zhang, Yongqian; Liu, Yahui; Deng, Yulin

    It has been found that microgravity may lead to impairments in cognitive functions performed by CNS. However, the exact mechanism of effects of microgravity on the learning and memory function in animal nervous system is not elucidated yet. Brain function is mainly mediated by membrane proteins and their dysfunction causes degeneration of the learning and memory. To induce simulated microgravity, the rat tail suspension model was established. Comparative O (18) labeling quantitative proteomic strategy was applied to detect the differentially expressed proteins in rat brain hippocampus. The proteins in membrane fraction from rat hippocampus were digested by trypsin and then the peptides were separated by off-gel for the first dimension with 24 wells device encompassing the pH range of 3 - 10. An off-gel fraction was subjected into LC-ESI-QTOF in triplicate. Preliminary results showed that nearly 77% of the peptides identified were specific to one fraction. 676 proteins were identified among which 108 proteins were found differentially expressed under simulated microgravity. Using the KOBAS server, many enriched pathways, such as metabolic pathway, synaptic vesicle cycle, endocytosis, calcium signaling pathway, and SNAREs pathway were identified. Furthermore, it has been found that neurotransmitter released by Ca (2+) -triggered synaptic vesicles fusion may play key role in neural function. Rab 3A might inhibit the membrane fusion and neurotransmitter release. The protein alteration of the synaptic vesicle cycle may further explain the effects of microgravity on learning and memory function in rats. Key words: Microgravity; proteomics; synaptic vesicle; O (18) ({}) -labeling

  10. The role of the hippocampus in passive and active spatial learning.

    Science.gov (United States)

    Kosaki, Yutaka; Lin, Tzu-Ching Esther; Horne, Murray R; Pearce, John M; Gilroy, Kerry E

    2014-12-01

    Rats with lesions of the hippocampus or sham lesions were required in four experiments to escape from a square swimming pool by finding a submerged platform. Experiments 1 and 2 commenced with passive training in which rats were repeatedly placed on the platform in one corner-the correct corner-of a pool with distinctive walls. A test trial then revealed a strong preference for the correct corner in the sham but not the hippocampal group. Subsequent active training of being required to swim to the platform resulted in both groups acquiring a preference for the correct corner in the two experiments. In Experiments 3 and 4, rats were required to solve a discrimination between different panels pasted to the walls of the pool, by swimming to the middle of a correct panel. Hippocampal lesions prevented a discrimination being formed between panels of different lengths (Experiment 3), but not between panels showing lines of different orientations (Experiment 4); rats with sham lesions mastered both problems. It is suggested that an intact hippocampus is necessary for the formation of stimulus-goal associations that permit successful passive spatial leaning. It is further suggested that an intact hippocampus is not necessary for the formation of stimulus-response associations, except when they involve information about length or distance. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.

  11. Red Wine Prevents the Acute Negative Vascular Effects of Smoking.

    Science.gov (United States)

    Schwarz, Viktoria; Bachelier, Katrin; Schirmer, Stephan H; Werner, Christian; Laufs, Ulrich; Böhm, Michael

    2017-01-01

    Moderate consumption of red wine is associated with fewer cardiovascular events. We investigated whether red wine consumption counteracts the adverse vascular effects of cigarette smoking. Participants smoked 3 cigarettes alone or after drinking a titrated volume of red wine. Clinical chemistry, blood counts, plasma cytokine enzyme-linked immunosorbent assays, immunomagnetic separation of CD14+ monocytes for gene expression analysis, fluorescence-activated cell sorting for microparticles, and isolation of circulating mononuclear cells to measure telomerase activity were performed, and urine cotinine levels were quantified. Compared with baseline, leukocytosis (P = .019), neutrophilia (P wine consumption. Cigarette smoke results in acute endothelial damage, vascular and systemic inflammation, and indicators of the cellular aging processes in otherwise healthy nonsmokers. Pretreatment with red wine was preventive. The findings underscore the magnitude of acute damage exerted by cigarette smoking in "occasional lifestyle smokers" and demonstrate the potential of red wine as a protective strategy to avert markers of vascular injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Preventing blood transfusion failures: FMEA, an effective assessment method.

    Science.gov (United States)

    Najafpour, Zhila; Hasoumi, Mojtaba; Behzadi, Faranak; Mohamadi, Efat; Jafary, Mohamadreza; Saeedi, Morteza

    2017-06-30

    Failure Mode and Effect Analysis (FMEA) is a method used to assess the risk of failures and harms to patients during the medical process and to identify the associated clinical issues. The aim of this study was to conduct an assessment of blood transfusion process in a teaching general hospital, using FMEA as the method. A structured FMEA was recruited in our study performed in 2014, and corrective actions were implemented and re-evaluated after 6 months. Sixteen 2-h sessions were held to perform FMEA in the blood transfusion process, including five steps: establishing the context, selecting team members, analysis of the processes, hazard analysis, and developing a risk reduction protocol for blood transfusion. Failure modes with the highest risk priority numbers (RPNs) were identified. The overall RPN scores ranged from 5 to 100 among which, four failure modes were associated with RPNs over 75. The data analysis indicated that failures with the highest RPNs were: labelling (RPN: 100), transfusion of blood or the component (RPN: 100), patient identification (RPN: 80) and sampling (RPN: 75). The results demonstrated that mis-transfusion of blood or blood component is the most important error, which can lead to serious morbidity or mortality. Provision of training to the personnel on blood transfusion, knowledge raising on hazards and appropriate preventative measures, as well as developing standard safety guidelines are essential, and must be implemented during all steps of blood and blood component transfusion.

  13. Effect of revised nursery orders on newborn preventive services.

    Science.gov (United States)

    Madlon-Kay, Diane J

    2011-01-01

    Aspects of neonatal care that are the subject of evolving guidelines include hepatitis B virus (HBV) immunization; discharge follow-up recommendations; and prevention of perinatal group B streptococcal (GBS) disease. In 2007, a university hospital's standardized newborn nursery orders were changed to reflect current recommendations in these areas. The objective of the study was to determine the effect of new nursery orders on the quality of care provided to these newborns. The study was a retrospective review of medical records, birth certificates, and a computer database of 857 infants. The nursery orders changed in the following ways: (1) physicians had to "opt out" of HBV immunization; (2) discharge follow-up recommendations were based on American Academy of Pediatrics (AAP) recommendations; and (3) AAP recommendations for GBS were followed except blood cultures were not required for certain infants. The percentage of infants receiving HBV immunizations increased from 74% in 2007 to 83% in 2008 (P = .0018). The percentage of infants whose mothers received antibiotics for GBS less than 4 hours before delivery and who received a complete blood count increased from 36% to 83% (P nursery orders was associated with significant improvement in newborn care.

  14. Effectiveness of waste prevention program in primary students' schools.

    Science.gov (United States)

    Zorpas, Antonis A; Voukkali, Irene; Loizia, Pantelitsa

    2017-06-01

    Even though reducing waste is at the top of the waste hierarchy, no real decoupling between waste generation and consumption has been demonstrated. Several waste directives had been published from EU, but they have only brought minor changes within the key objective of reducing waste generation. Most efforts have been targeted towards greater amounts of recycling and better management of waste disposal. While these are necessary and socially beneficial goals, they are not adequate for the achievement of long-term sustainability goals. The purpose of this study is to understand students' knowledge, attitudes and behavioural changes in relation to the water plastic bottle of 500 ml. Understanding waste prevention behaviour (WPB) could enable schools' principals, local authorities and committees as well as decision makers to design and implement more effective policies for reducing the amount of specific waste streams that is generated. Students in a daily base bring their own water containers of 500 ml or buy water from the school as they do not feel safe to use other sources of water. Nine hundred ninety-eight refilling stainless steel water refilling bottles (SSWRB-of 600 ml) were shared to the students in four primary schools. The results indicated that the students are presented with different behaviours from class to class for many reasons; most of them are related with what their parents believe, and how themselves or the synergies between them reacts and affected.

  15. Hesperidin inhibits glutamate release and exerts neuroprotection against excitotoxicity induced by kainic acid in the hippocampus of rats.

    Science.gov (United States)

    Chang, Chia Ying; Lin, Tzu Yu; Lu, Cheng Wei; Huang, Shu Kuei; Wang, Ying Chou; Chou, Shang Shing Peter; Wang, Su Jane

    2015-09-01

    The citrus flavonoid hesperidin exerts neuroprotective effects and could cross the blood-brain barrier. Given the involvement of glutamate neurotoxicity in the pathogenesis of neurodegenerative disorders, this study was conducted to evaluate the potential role of hesperidin in glutamate release and glutamate neurotoxicity in the hippocampus of rats. In rat hippocampal nerve terminals (synaptosomes), hesperidin inhibited the release of glutamate and elevation of cytosolic free Ca(2+) concentration evoked by 4-aminopyridine (4-AP), but did not alter 4-AP-mediated depolarization. The inhibitory effect of hesperidin on evoked glutamate release was prevented by chelating the extracellular Ca(2+) ions and blocking the activity of Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels or protein kinase C. In hippocampal slice preparations, whole-cell patch clamp experiments showed that hesperidin reduced the frequency of spontaneous excitatory postsynaptic currents without affecting their amplitude, indicating the involvement of a presynaptic mechanism. In addition, intraperitoneal (i.p.) injection of kainic acid (KA, 15 mg/kg) elevated the extracellular glutamate levels and caused considerable neuronal loss in the hippocampal CA3 area. These KA-induced alterations were attenuated by pretreatment with hesperidin (10 or 50 mg/kg, i.p.) before administering the KA. These results demonstrate that hesperidin inhibits evoked glutamate release in vitro and attenuates in vivo KA-induced neuronal death in the hippocampus. Our findings indicate that hesperidin may be a promising candidate for preventing or treating glutamate excitotoxicity related brain disorders such as neurodegenerative diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. The fatty acid amide hydrolase inhibitor URB597 exerts anti-inflammatory effects in hippocampus of aged rats and restores an age-related deficit in long-term potentiation

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    Murphy Niamh

    2012-04-01

    Full Text Available Abstract Background Several factors contribute to the deterioration in synaptic plasticity which accompanies age and one of these is neuroinflammation. This is characterized by increased microglial activation associated with increased production of proinflammatory cytokines like interleukin-1β (IL-1β. In aged rats these neuroinflammatory changes are associated with a decreased ability of animals to sustain long-term potentiation (LTP in the dentate gyrus. Importantly, treatment of aged rats with agents which possess anti-inflammatory properties to decrease microglial activation, improves LTP. It is known that endocannabinoids, such as anandamide (AEA, have anti-inflammatory properties and therefore have the potential to decrease the age-related microglial activation. However, endocannabinoids are extremely labile and are hydrolyzed quickly after production. Here we investigated the possibility that inhibiting the degradation of endocannabinoids with the fatty acid amide hydrolase (FAAH inhibitor, URB597, could ameliorate age-related increases in microglial activation and the associated decrease in LTP. Methods Young and aged rats received subcutaneous injections of the FAAH inhibitor URB597 every second day and controls which received subcutaneous injections of 30% DMSO-saline every second day for 28 days. Long-term potentiation was recorded on day 28 and the animals were sacrificed. Brain tissue was analyzed for markers of microglial activation by PCR and for levels of endocannabinoids by liquid chromatography coupled to tandem mass spectrometry. Results The data indicate that expression of markers of microglial activation, MHCII, and CD68 mRNA, were increased in the hippocampus of aged, compared with young, rats and that these changes were associated with increased expression of the proinflammatory cytokines interleukin (IL-1β and tumor necrosis factor-α (TNFα which were attenuated by treatment with URB597. Coupled with these changes, we

  17. Effectiveness and cost-effectiveness of behavioural strategies in the prevention of cigarette smoking

    Directory of Open Access Journals (Sweden)

    Willich, Stefan N.

    2008-10-01

    Full Text Available Background: The hazardous health effects of smoking and second hand smoke have been confirmed in numerous studies. For Germany, the mortality attributable to smoking is estimated at 110,000 to 140,000 deaths per year, associated with annual smoking-related costs of 17 to 21 billion euro. Because the majority of smokers initiate this habit early in life, behavioural preventive strategies usually tried to prevent the uptake of smoking among children and youths. Objectives: The goal of this HTA is to summarise the current literature on behavioural strategies for smoking prevention and to evaluate their medical effectiveness/efficacy and cost-effectiveness as well as the ethical, social and legal implications of smoking prevention programs. In addition, this report aims to compare the effectiveness and efficacy of different intervention components and to evaluate the reliability of results in the German context. Methods: Relevant publications were identified by means of a structured search of databases accessed through the German Institute of Medical Documentation and Information (DIMDI. In addition a manual search of identified reference lists was conducted. The present report includes German and English literature published between August 2001 and August 2006 targeting youths up to 18 years old. The methodological quality of included studies was assessed according to pre-defined quality criteria, based on the criteria of evidence-based medicine. Results: Among 3,580 publications 37 medical studies met the inclusion criteria. Overall study quality was satisfactory but only half the studies reported smoking uptake as an outcome, while the remaining studies reported alternative outcome parameters. The follow-up duration varied between twelve and 120 months. Although overall effectiveness of prevention programs showed considerable heterogeneity, there was evidence for the long-term effectiveness of behavioural smoking prevention programs. However, the

  18. Adolescent Smoking Prevention: Feasibility and Effect of Participatory Video Production.

    Science.gov (United States)

    Park, Eunhee; Kulbok, Pamela A; Keim-Malpass, Jessica; Drake, Emily; Kennedy, Michael J

    This study tested whether a youth participatory video production program for smoking prevention is feasible and effective. A participatory video production program was implemented in eight twice-weekly sessions at a youth summer camp in a community center in a low-income neighborhood. Twenty-three youths participated. Descriptive statistics and a qualitative analysis were conducted to test the feasibility of the program by assessing attendance rates, the time and resources required, reasons for participation, and program satisfaction using checklists and interviews. Smoking intention was measured via pre- and post-intervention surveys and a quantitative analysis utilizing a Wilcoxon Signed Rank test to detect differences in intention for non-smoking. Participants worked in groups to produce four video clips containing anti-smoking messages. Three main themes (active engagement, participation for community health, and personal growth and healthy development) emerged from the qualitative interview data. >75% of the participants considered the program excellent and stated that it met their expectations. Significant positive changes were also found from baseline to post-intervention in intention not to smoke. This study demonstrated the effect of a participatory digital media production approach and confirmed its feasibility for youth health promotion and health education. Participants' active involvement in producing anti-smoking videos for a community health-promotion campaign decreased their intention to smoke and empowered them as advocates for a non-smoking community. These findings confirm the feasibility and utility of digital media use and interactive technology for actively engaging young people in health promotion. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Xiaoyaosan Decoction, a Traditional Chinese Medicine, Inhibits Oxidative-Stress-Induced Hippocampus Neuron Apoptosis In Vitro

    Directory of Open Access Journals (Sweden)

    Zhen-zhi Meng

    2012-01-01

    Full Text Available Xiaoyaosan (XYS decoction is a famous prescription for the treatment of mental disorders in China. In this experiment, we explored the way in which XYS decoction-reverse hippocampus neuron apoptosis in vitro. We used XYS decoction-containing serum to treat oxidative-stress-induced hippocampus neuron apoptosis and used immunofluorescence to determine the concentration of free calcium, mitochondrial membrane potential, and apoptotic rate of neuron. Results showed that 3-hour oxidative stress decrease mitochondrial membrane potential, increase the concentration of free calcium and apoptotic rate of neuron via triggering pathological changes of nucleus such as karyorrhexis, karyopyknosis. Low, medium, high dose of XYS-decoction-containing serum could reverse these phenomenon, and the effect of low-dose XYS-decoction-containing serum was significant in improving mitochondrial membrane potential and apoptotic rate of neuron. These findings suggest that XYS decoction may be helpful in reducing oxidative-stress-induced hippocampus neuron apoptosis.

  20. Physical Exercise Habits Correlate with Gray Matter Volume of the Hippocampus in Healthy Adult Humans

    Science.gov (United States)

    Killgore, William D. S.; Olson, Elizabeth A.; Weber, Mareen

    2013-12-01

    Physical activity facilitates neurogenesis of dentate cells in the rodent hippocampus, a brain region critical for memory formation and spatial representation. Recent findings in humans also suggest that aerobic exercise can lead to increased hippocampal volume and enhanced cognitive functioning in children and elderly adults. However, the association between physical activity and hippocampal volume during the period from early adulthood through middle age has not been effectively explored. Here, we correlated the number of minutes of self-reported exercise per week with gray matter volume of the hippocampus using voxel-based morphometry (VBM) in 61 healthy adults ranging from 18 to 45 years of age. After controlling for age, gender, and total brain volume, total minutes of weekly exercise correlated significantly with volume of the right hippocampus. Findings highlight the relationship between regular physical exerci