The effect of tacrine (THA) on cycloheximide- and basal forebrain lesion-induced memory deficit in rats.

The effects of 9-amino-1,2,3,4-tetrahydroacridine (tacrine), an active acetylcholinesterase inhibitor, on cycloheximide- and basal forebrain (BF) lesion-induced memory deficit in the water maze and passive avoidance task were investigated. While cycloheximide (1.5 mg/kg, s.c.) produced amnesia in the passive avoidance task, chronic administration of tacrine (1, 3 and 10 mg/kg, once a day for 1 week) improved the amnesia. BF lesion produced amnesia in both the water maze and passive avoidance tasks. Chronic tacrine (0.1-3 mg/kg, passive avoidance task, or 0.3 mg/kg, water maze task, once a day for 1 week) improved BF lesion-induced amnesia in the passive avoidance and water maze tasks. These results suggest that tacrine may be useful for senile dementia.     

Joint effects of medial septal lesions and amylobarbitone injections on resistance to extinction in the rat

32 male rats, of which half had sustained small electrolytic lesions in the medial septal area and half had received sham operations, were trained on continuous reinforcement to run an alley for water reward and then given four days of extinction testing. Half of both the lesioned and sham-operated groups were given sodium amylobarbitone on Days 1 and 2 of extinction and the other half on Days 3 and 4, saline being administered on non-drug days. The drug, unusually, decreased resistance to extinction. This effect was probably due to the subjects having taken part in a previous experiment in which they had received, without drugs, training and extinction under the same conditions as in this experiment. In the goal section of the alley, the drug effect was greater in lesioned than shamoperated rats. The lesions retarded extinction, and this effect was reduced by the drug. A model for the neural loci at which amylobarbitone acts to affect resistance to extinction, based on these and other results, is proposed.     

石杉碱甲对基底核大细胞部损毁所致工作记忆障碍的影响

目的：研究石杉碱甲对基底核大细胞部（ＮＢＭ）损毁诱导的工作记忆障碍的影响。方法：采用八臂迷宫延迟板程序研究空间记忆。胆碱乙酰转移酶（ＣｈＡＴ）活力测定采用［＾３Ｈ］乙酰辅酶Ａ转变成［＾３Ｈ］乙酰胆碱的方法。结果：单侧损毁ＮＢＭ（卡因酸０．０２μｍｏｌ）导致空间记忆障碍。在不同的延迟间隔，大鼠完成程序产生的正确数减少和错误数增多。损毁侧大脑皮层ＣｈＡＴ酶的含量下降了大约４０％。石杉碱甲（０．２ｍｇ·     

The medial entorhinal cortex mediates basolateral amygdala effects on spatial memory and downstream activity-regulated cytoskeletal-associated protein expression

The basolateral amygdala (BLA) modulates the consolidation of dorsal hippocampus (DH)-dependent spatial and dorsolateral striatum (DLS)-dependent cued-response memories, often in competition with one another. Evidence suggests that a critical mechanism for BLA influences on memory consolidation is via effects on activity-regulated cytoskeletal-associated protein (ARC) in downstream brain regions. However, the circuitry by which the BLA modulates ARC in multiple competing memory systems remains unclear. Prior evidence indicates that optogenetic stimulation of BLA projections to the medial entorhinal cortex (mEC) enhances the consolidation of spatial learning and impairs the consolidation of cued-response learning, suggesting this pathway provides a circuit for favoring one system over another. Therefore, we hypothesized the BLA-mEC pathway mediates effects on downstream ARC-based synaptic plasticity related to these competing memory systems. To address this, male and female Sprague–Dawley rats underwent spatial or cued-response Barnes maze training and, 45 min later, were sacrificed for ARC analysis in synaptoneurosomes from the DH and DLS. Initial experiments found that spatial training alone increased ARC levels in the DH above those observed in control rats and rats that underwent a cued-response version of the task. Postspatial training optogenetic stimulation of the BLA–mEC pathway altered the balance of ARC expression in the DH vs. DLS, specifically shifting the balance in favor of the DH-based spatial memory system, although the precise region of ARC changes differed by sex. These findings suggest that BLA–mEC pathway influences on ARC in downstream regions are a mechanism by which the BLA can favor one memory system over another.Subject terms: Cognitive neuroscience, Consolidation, Synaptic plasticity, Hippocampus     

Effects of ACTH and related peptides on medial septal self-stimulation

The effects of ACTH1-24, ACTH4-10, the ACTH4-9 analog Org 2766 and [D-Phe7] ACTH4-10 on medial septal self-stimulation were determined in the rat following intracerebroventricular (ICV) injections. Self-stimulation rates were increased by 0.01-10 micrograms ACTH1-24 or 0.1-10 micrograms ACTH4-10, but not by Org 2766 or [D-Phe7] ACTH4-10. A dose of 1 microgram ACTH1-24 ICV did not affect open field behaviour. Subcutaneous administration of 1 microgram ACTH1-24 did not influence self-stimulation in the septum. Thus, the ACTH1-24 effect appears to be a central effect and provides evidence for an influence of ACTH containing pathways on structures involved in maintaining self-stimulation behavior. A possible role of opiate receptors and dopaminergic neurons in this effect of ACTH1-24 is also discussed.     

Tianeptine and its enantiomers: effects on spatial memory in rats with medial septum lesions

Tianeptine, an atypical antidepressant that exhibits clinical efficacy in measures of depression and anxiety, has been reported to enhance learning and memory in rats under certain conditions, an effect not observed with other tricyclic antidepressants. The present study explores further the possibility that tianeptine or its enantiomers (S 16190 and S 16191) can enhance either learning or retention in animals in which the hippocampus has been made partially dysfunctional. The effects of tianeptine and its enantiomers were tested using an open field watermaze test, in rats with partial lesions of the medial septum/diagonal band of Broca (MSDB). When given to normal rats, tianeptine (10 mg/kg, i.p.) did not significantly affect learning as compared to animals injected with saline. We therefore created, in other animals, partial ibotenic acid lesions of MSDB and showed histochemically that these lesions reduced but did not abolish the density of acetylcholinesterase staining in the hippocampus. They impaired both the acquisition of place-navigation and the long-term retention of spatial information over 7 days. Against the baseline of impaired performance in animals with these lesions, neither tianeptine (10 mg/kg) nor its enantiomers (5 mg/kg) affected the rate of acquisition of place navigation. However, tianeptine did enhance the retention of spatial memory over 7 days. These results are discussed in relation to different effects that tianeptine may have on learning including its ability to block stress-induced dendritic re-modelling of the hippocampus.     

Prenatally protein-malnourished rats are less sensitive to the amnestic effects of medial septal infusions of chlordiazepoxide

Evidence is mounting that prenatal protein malnutrition affects the physiological properties of the GABAergic neurotransmitter system in rats. To investigate the functional behavioral consequences of these changes, chlordiazepoxide (CDP, a positive modulator of the GABA(A) receptor) was applied directly to the medial septum and the amnestic response appraised. In adulthood, male offspring of rats provided with a protein-deficient diet (6% casein) for 5 weeks prior to mating and throughout pregnancy underwent stereotaxic surgery to implant steel cannulae aimed at the medial septum. After recovery, spatial learning performance in the submerged platform version of the Morris water maze task was assessed immediately following a 1 microl infusion of either artificial cerebrospinal fluid (aCSF), or one of three doses of CDP (15, 30 and 60 nmol). Well-nourished control rats demonstrated a robust amnestic response to intraseptal CDP. During task acquisition, well-nourished rats administered each of the doses exhibited significantly longer escape latencies than those given aCSF. On the probe trial (platform removed) a lower proportion of time was spent in the target quadrant (all three doses) at a greater average distance from the former platform location (30 and 60 nmol doses). In contrast, prenatally malnourished rats exhibited a muted sensitivity to CDP, most notable at the 30 nmol dose. These findings provide further support for functional changes within the GABAergic system consequent to malnutrition.     

经胸超声心动图在继发孔型房间隔缺损封堵术中的应用

目的探讨经胸超声心动图(TTE)在继发孔型房间隔缺损(ASD)封堵术中的应用价值。方法应用TTE筛选27例继发孔型ASD患者,经TTE引导进行封堵术。结果 27例患者成功进行了Amplatzer封堵术,24例无残余分流,3例残余分流(<2mm),术后1个月复查分流消失。结论 TTE在ASD介入治疗中起重要作用。     

心间隔缺损并双向分流患儿的围术期治疗

目的　提高重症先天性心脏病患儿的成活率。方法　随机选择 32例拟行手术治疗的心间隔缺损并重度肺动脉高压、双向分流的患儿为研究对象。年龄 4个月～ 12岁 ,平均 4 3岁 ,体重 4 5～ 2 7kg ,平均 9 6kg,≤2岁者 18例 ,>2岁者 14例 ;单纯室间隔缺损 16例 ,室间隔 +房间隔缺损 5例 ,室间隔缺损 +动脉导管未闭 7例 ,室间隔缺损 +房间隔缺损 +动脉导管未闭 3例 ,完全性心内膜垫缺损 1例。术前采用合适的药物治疗 ,控制肺动脉压达满意水平 10～ 15d ,术后坚持使用药物治疗的同时延长呼吸机辅助时间 ,以维持适宜的血气指标在满意的水平。结果　本组 32例 ,治愈 2 9例 ,术后并发肺高压危象 9例 ,右心功能衰竭 3例 ,频发室性早搏 3例 ,低心输出量综合征 4例 ,共死亡 3例。结论　对心间隔缺损并重度肺动脉高压、双向分流者的围术期综合治疗是提高手术成功率的重要环节     

Dopaminergic agents including 3-PPP and its enantiomers on medial septal self-stimulation

The effects of several dopamine agonists were determined on medial septal self-stimulation in rats and compared with selected dopamine antagonists and with the psychostimulants, d-amphetamine and nomifensine. Apomorphine, 3-PPP, TL-99, N,N-dipropyl-5,6-ADTN and N,N-dipropyl-6,7-ADTN inhibited self-stimulation at dose ranges selective for the dopamine autoreceptor as indicated by biochemical studies. Haloperidol and molindone produced dose-related inhibition but sulpiride increased self-stimulation. D-amphetamine and nomifensine also increased responding. The agonist-induced inhibition differed from neuroleptic-induced inhibition of self-stimulation. Both (+) and (-) 3-PPP inhibited responding by a similar amount over the dose range 0.25-1.0 mg/kg. At higher doses, (-) 3-PPP further decreased responding whereas the effects of (+) 3-PPP plateaued at approximately 55% of controls. These studies show that dopamine agonists, like neuroleptics, inhibit medial septal self-stimulation. This effect appears to be mediated via autoreceptor activation. Differences between neuroleptic- and agonist-induced inhibition and the 3-PPP stereoisomer data accord with the hypothesis that behavioural inhibitory effects caused by autoreceptor activation are less severe than those caused by dopamine postsynaptic blockade.     

The effects of black garlic on the working memory and pyramidal cell number of medial prefrontal cortex of rats exposed to monosodium glutamate

Monosodium glutamate-induced exitotoxicity causes oxidative stress in many brain areas, including the medial prefrontal cortex. The ethanolic garlic (Allium sativum) extract is considered as a neuroprotective substance. The present study aimed at investigating the effects of the ethanolic fermented garlic extract on the working memory and the pyramidal cell number of the medial prefrontal cortex of adolescent male Wistar rats exposed to monosodium glutamate (MSG). Twenty-five rats were randomly divided into five groups. The C– group was given 0.9% NaCl solution. The C?+?group was given 2?mg/g bw of MSG. The T1, T2, and T3 groups were given MSG and garlic extract (0.0125, 0.025, and 0.05?mg/g bw, respectively). All treatments were conducted for 10?days. The working memory capability of the rats was measured using Y-maze test. The total number of pyramidal cells of the medial prefrontal cortex was estimated using physical fractionator method. The working memory performances of the T1, T2, and T3 groups were significantly better than that of the C?+?group. There were no significant differences between groups in the estimated total number of pyramidal cell of medial prefrontal cortex. The MSG may not cause the death of neurons, but it may modify neuronal architectures that are sufficient to disrupt memory functions. Black garlic may play a role as an antioxidant agent that prevents the prefrontal cortex from glutamate-induced oxidative stress. It is concluded that the ethanolic fermented garlic extract prevented the working memory impairment following MSG administration.     

Comparative study of the effects of tianeptine and other antidepressants on the activity of medial septal neurons in rats anesthetized with urethane

Summary Tianeptine is a tricyclic antidepressant which enhances serotonin uptake in certain brain areas. Tianeptine has been reported to improve both working and reference memories in rodents. The effects of tianeptine on the spontaneous activity of medial septal neurons were studied in rats anesthetized with urethane. Systemic administrations (0.2–1 mg/kg i. v.) of tianeptine decreased the spontaneous activity and disorganized or suppressed the rhythmically bursting activity of medial septal neurons, in a dose related manner. Iontophoretic administrations of tianeptine did not modify the spontaneous activity of medial septal neurons. Changes of the bursting activity were inconsistent. However, tianeptine blocked partially or completely the inhibition induced by the serotonin in 68% of the cases. In contrast, other antidepressants (amitriptyline, clomipramine and fluoxetine) potentiated the inhibitory effect of serotonin in 50%–60% of the cases. Our results show that tianeptine, applied by iontophoresis, has an effect on the medial septal neurons which was opposite to that of other antidepressants. On the basis of our findings, it can be tentatively proposed that tianeptine may have a beneficial effect on memory by counteracting the serotonin-induced inhibition of medial septal neurons. Send offprint requests to M. H. Bassant at the above address     

The effects of scopolamine on retrieval from semantic memory

The effects of two doses of scopolamine (0.6 and 1.2 mg p.o.) on retrieval from semantic memory in normal young volunteers were examined using tests of verbal fluency and categorization latency. A visual contrast sensitivity test, which has previously shown a scopolamine-induced impairment at these doses (Broks et al., 1988), was also administered. In agreement with the work of Dunne (1990) and others, no evidence for a scopolamine deficit in semantic retrieval was found; in fact scopolamine improved letter fluency. However, scopolamine did produce the expected decrease in visual contrast sensitivity. The doses of scopolamine used here have also been shown to impair learning and attention (Broks et al., 1988). It is possible that earlier studies which found a scopolamine deficit on semantic retrieval, did so because they used elderly subjects and/or large drug doses.     

Ventricular septal defects in function of maternal sociodemographic aspects

The objective of our project is to reveal the possible etiological factors of different congenital cardiovascular abnormalities. In this study, we evaluated single ventricular septal defect (VSD) after surgical correction or with lethal outcome. The birth outcomes of these cases in the function of maternal socio-demographic features were evaluated. Data are based on 1,659 VSD cases, 2,534 matched controls and 38,151 all controls without any defects, in addition in the mothers of 19,393 malformed controls with other isolated defects in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities. VSD had mild female excess with a higher rate of preterm birth and mainly low birth weight indicating intrauterine growth restriction of affected fetuses, particularly in males and full-term or average weighted cases. The mothers of cases with VSD had lower socioeconomic status and higher rate of smoking and particularly drinking habit. The evaluation of medically recorded pregnancy complications showed an association of gestational diabetes with a higher risk of VSD. In conclusion, the association of small localized size of VDS and obvious fetal growth restriction needs further explanation in these cases, while gestational diabetes, lower socioeconomic status and adverse lifestyle of pregnant women may have a role in the origin of VSD.     

The substrates of memory: defects, treatments, and enhancement

Recent work has added strong support to the long-standing hypothesis that the stabilization of both long-term potentiation and memory requires rapid reorganization of the spine actin cytoskeleton. This development has led to new insights into the origins of cognitive disorders, and raised the possibility that a diverse array of memory problems, including those associated with diabetes, reflect disturbances to various components of the same mechanism. In accord with this argument, impairments to long-term potentiation in mouse models of Huntington's disease and in middle-aged rats have both been linked to problems with modulatory factors that control actin polymerization in spine heads. Complementary to the common mechanism hypothesis is the idea of a single treatment for addressing seemingly unrelated memory diseases. First tests of the point were positive: Brain-Derived Neurotrophic Factor (BDNF), a potent activator of actin signaling cascades in adult spines, rescued potentiation in Huntington's disease mutant mice, middle-aged rats, and a mouse model of Fragile-X syndrome. A similar reversal of impairments to long-term potentiation was obtained in middle-aged rats by up-regulating BDNF production with brief exposures to ampakines, a class of drugs that positively modulate AMPA-type glutamate receptors. Work now in progress will test if chronic elevation of BDNF enhances memory in normal animals.