Effects of Hippocampal Microinjection of Irisin,an Exercise-Induced Myokine,on Spatial and Passive Avoidance Learning and Memory in Male Rats

International Journal of Peptide Research and Therapeutics - Irisin is a soluble and exercise-induced myokine and/or adipokine hormone; generated by FNDC5 (a gene precursor) and also, it can...     

慢性应激抑郁大鼠学习记忆及海马非对称性超微结构的改变

目的：探讨慢性不可预见性应激抑郁模型大鼠大脑海马非对称性超微结构与学习记忆能力的改变。方法：SD雄性大鼠20只,随机分为正常对照组与抑郁模型组,每组10只。采用慢性轻度不可预见性应激21d及单笼饲养方法建立抑郁模型,应激前以及应激21d末对两组大鼠进行旷场实验、液体消耗实验及体重测量,对大鼠进行避暗穿梭实验,测试其学习记忆能力,之后活杀动物,取出大鼠左右海马,制作常规电镜标本,观察海马超微结构的改变。结果：在穿梭变实验中抑郁大鼠学习记忆潜伏期减少,进入暗箱错误积分增多。抑郁大鼠左右侧海马超微结构中左侧海马较正常对照组神经细胞及胶质细胞变化明显,表现为内质网扩张,溶酶体增多。而右侧海马远不及左侧损伤严重。结论：慢性不可预见性应激抑郁大鼠学习记忆能力显著下降,其可能与海马组织在应激过程受到的累积损伤有关,且抑郁大鼠海马损伤呈非对称表现。     

Effects of Methamphetamine Exposure on Fear Learning and Memory in Adult and Adolescent Rats

Methamphetamine (meth) use is often comorbid with anxiety disorders, with both conditions predominant during adolescence. Conditioned fear extinction is the most widely used model to study the fear learning and regulation that are relevant for anxiety disorders. The present study investigates how meth binge injections or meth self-administration affect subsequent fear conditioning, extinction and retrieval in adult and adolescent rats. In experiment 1, postnatal day 35 (P35—adolescent) and P70 (adult) rats were intraperitoneally injected with increasing doses of meth across 9 days. At P50 or P85, they underwent fear conditioning followed by extinction and test. In experiments 2a–c, P35 or P70 rats self-administered meth for 11 days then received fear conditioning at P50 or P85, followed by extinction and test. We observed that meth binge exposure caused a significant disruption of extinction retrieval in adult but not adolescent rats. Interestingly, meth self-administration in adolescence or adulthood disrupted acquisition of conditioned freezing in adulthood. Meth self-administration in adolescence did not affect conditioned freezing in adolescence. These results suggest that intraperitoneal injections of high doses of meth and meth self-administration have dissociated effects on fear conditioning and extinction during adulthood, while adolescent fear conditioning and extinction are unaffected.

     

早期游泳运动对慢性温和应激抑郁大鼠学习和记忆能力的影响

目的:探讨早期游泳运动对慢性温和应激(chronic mild stress,CMS)大鼠学习和记忆能力的影响。方法:50只SD大鼠随机分成5组:对照组、模型组、低强度运动组、中等强度运动组、高强度运动组。运动组大鼠按照游泳运动方案运动4 w,糖水消耗实验和强迫游泳实验评价大鼠抑郁程度;Morris水迷宫实验评价大鼠学习记忆能力。结果:模型组大鼠糖水消耗量和游泳不动时间较对照组明显降低(P0.01),低强度运动组和中等强度运动组大鼠较模型组糖水消耗量和游泳不动时间明显增加(P0.05或P0.01);模型组大鼠较对照组逃避潜伏期明显延长,目标象限搜索时间占总游泳时间的百分比和目标象限穿过次数减少,体质量、双侧海马质量和海马相对质量下降(P0.05或P0.01);低强度运动组和中等强度运动组大鼠较模型组比较,潜伏期缩短明显,目标象限搜索时间占总游泳时间的百分比和目标象限穿过次数增加,体质量、双侧海马质量和海马相对质量增加(P0.05或P0.01)。结论:早期游泳运动能减轻慢性温和应激抑郁大鼠的学习记忆的损害,其中低强度和中等强度运动训练作用效果最佳。     

Effects of Ifenprodil on Morphine-Induced Conditioned Place Preference and Spatial Learning and Memory in Rats

Drug addiction, as well as learning and memory, share common mechanisms in terms of neural circuits and intracellular signaling pathways. In the present study, the role of N-methyl-D-aspartate (NMDA) receptors, particularly those containing NR2B subunits, in morphine-induced conditioned place preference (CPP) and Morris water maze (MWM) learning and memory task was investigated. CPP was used as a paradigm for assessing the rewarding effect of morphine, and MWM was used to measure spatial learning and memory in male Sprague–Dawley rats. We found that ifenprodil, an antagonist highly selective for NR2B-containing NMDA receptors, dose-dependently blocked the development, maintenance and reinstatement of morphine-induced CPP, without evident impairment of the acquisition and retrieval of spatial memory in the MWM task. However, the consolidation of spatial memory was disrupted by a high dose (10 mg/kg) of ifenprodil. These results clearly demonstrate that NR2B-containing NMDA receptors are actively involved in addiction memory induced by morphine conditioning, but not in the acquisition and retrieval of spatial learning and memory. In conclusion, NR2B-containing NMDA receptors can be considered potential targets for the treatment of opiate addiction.     

Combined Impact of Exercise and Temperature in Learning and Memory Performance of Fluoride Toxicated Rats

In previous studies, we investigated a link between high fluoride exposure and functional IQ deficits in rats. This study is an extension conducted to explore the combined influence of physical exercise and temperature stress on the learning ability and memory in rats and to assess whether any positive modulation could be attenuated due to exercise regimen subjected to F-toxicated animals at different temperatures. Accumulation of ingested fluoride resulted significant inhibition in acetylcholinesterase activity (P?<?0.05), plasma cortisol levels (P?<?0.05), and impaired the acquisition, performance, latency time, and retention in fluoride-exposed animals. Fluoride-toxicated rats took more number of sessions during the learning phase [F _{5, 35}?=?19.065; P?<?0.05] and post hoc analysis on the number of correct choices revealed that there was a significant effect of treatments [F _{5, 30}?=?15.763; P?<?0.05]; sessions [F _{8, 240}?=?58.698; P?<?0.05]; and also significant difference in the interactions [F _{40, 240}?=?1.583; P?<?0.05]. The latency data also revealed a significant difference between groups [F _{5, 30}?=?28.085; P?<?0.05]; time?=?[F _{8, 240}?=?136.314; P?<?0.05]; and there was a significant difference in the interactions [F _{40, 240}?=?2.090; P?<?0.05]. In order to ascertain if interdependence between fluoride concentrations and the foregoing free radical parameters, respective correlation coefficients were calculated and results clearly emphasize the positive role of exercise in the promotion of cognitive functions by decreasing fluoride levels in rat hippocampus. A significant recovery in cognitive function was noticed in all the exercised animals due to reduced burden of brain oxidative stress. In comparison to exercise regimens performed at different temperatures, high (35?°C) and low temperatures (20?°C) led to a slower acquisition and poor retention of the task when compared to thermo neutral temperatures (25 and 30?°C). Thus exercise up-regulate antioxidant defenses and promote learning abilities in fluorotic population.     

电休克对大鼠空间记忆及海马p-ERK活性的影响

目的:观察电休克对大鼠空间记忆和海马磷酸化细胞外调节蛋白激酶(p-ERK)活性的影响。方法:大鼠随机分为电休克组和伪电休克组,每组12只。电休克组每天给予电痉挛刺激,伪电休克组每天给予假电痉挛刺激,共10天;第11天用水迷宫检测各组大鼠的空间学习记忆,然后每组大鼠再随机分为两组,每组6只。一组于学习后1小时处死取海马用Western blot法检测p-ERK活性,另一组于48小时后行水迷宫空间位置探寻实验检测大鼠的存储记忆。结果:电休克组的潜伏期显著长于伪电休克组(P0.01)。电休克组在隐匿平台周围区域/相反区域的搜寻时间无显著性差异(P0.05);伪电休克组在隐匿平台周围区域/相反区域的搜寻时间有显著性差异(P0.05)。电休克组海马p-ERK活性较伪电休克组显著下降(P0.01)。结论:电休克可导致大鼠显著空间记忆障碍,海马p-ERK活性的降低可能是其机制之一。     

Effects of Exercise Intensity on Spatial Memory Performance and Hippocampal Synaptic Plasticity in Transient Brain Ischemic Rats

Memory impairment is commonly noted in stroke survivors, and can lead to delay of functional recovery. Exercise has been proved to improve memory in adult healthy subjects. Such beneficial effects are often suggested to relate to hippocampal synaptic plasticity, which is important for memory processing. Previous evidence showed that in normal rats, low intensity exercise can improve synaptic plasticity better than high intensity exercise. However, the effects of exercise intensities on hippocampal synaptic plasticity and spatial memory after brain ischemia remain unclear. In this study, we investigated such effects in brain ischemic rats. The middle cerebral artery occlusion (MCAO) procedure was used to induce brain ischemia. After the MCAO procedure, rats were randomly assigned to sedentary (Sed), low-intensity exercise (Low-Ex), or high-intensity exercise (High-Ex) group. Treadmill training began from the second day post MCAO procedure, 30 min/day for 14 consecutive days for the exercise groups. The Low-Ex group was trained at the speed of 8 m/min, while the High-Ex group at the speed of 20 m/min. The spatial memory, hippocampal brain-derived neurotrophic factor (BDNF), synapsin-I, postsynaptic density protein 95 (PSD-95), and dendritic structures were examined to document the effects. Serum corticosterone level was also quantified as stress marker. Our results showed the Low-Ex group, but not the High-Ex group, demonstrated better spatial memory performance than the Sed group. Dendritic complexity and the levels of BDNF and PSD-95 increased significantly only in the Low-Ex group as compared with the Sed group in bilateral hippocampus. Notably, increased level of corticosterone was found in the High-Ex group, implicating higher stress response. In conclusion, after brain ischemia, low intensity exercise may result in better synaptic plasticity and spatial memory performance than high intensity exercise; therefore, the intensity is suggested to be considered during exercise training.     

Exercise Is More Effective at Altering Gut Microbial Composition and Producing Stable Changes in Lean Mass in Juvenile versus Adult Male F344 Rats

The mammalian intestine harbors a complex microbial ecosystem that influences many aspects of host physiology. Exposure to specific microbes early in development affects host metabolism, immune function, and behavior across the lifespan. Just as the physiology of the developing organism undergoes a period of plasticity, the developing microbial ecosystem is characterized by instability and may also be more sensitive to change. Early life thus presents a window of opportunity for manipulations that produce adaptive changes in microbial composition. Recent insights have revealed that increasing physical activity can increase the abundance of beneficial microbial species. We therefore investigated whether six weeks of wheel running initiated in the juvenile period (postnatal day 24) would produce more robust and stable changes in microbial communities versus exercise initiated in adulthood (postnatal day 70) in male F344 rats. 16S rRNA gene sequencing was used to characterize the microbial composition of juvenile versus adult runners and their sedentary counterparts across multiple time points during exercise and following exercise cessation. Alpha diversity measures revealed that the microbial communities of young runners were less even and diverse, a community structure that reflects volatility and malleability. Juvenile onset exercise altered several phyla and, notably, increased Bacteroidetes and decreased Firmicutes, a configuration associated with leanness. At the genus level of taxonomy, exercise altered more genera in juveniles than in the adults and produced patterns associated with adaptive metabolic consequences. Given the potential of these changes to contribute to a lean phenotype, we examined body composition in juvenile versus adult runners. Interestingly, exercise produced persistent increases in lean body mass in juvenile but not adult runners. Taken together, these results indicate that the impact of exercise on gut microbiota composition as well as body composition may depend on the developmental stage during which exercise is initiated.     

右美托咪定对慢性应激抑郁妊娠大鼠子代发育及空间学习记忆能力的影响

妊娠期抑郁症可以通过影响孕妇的生理和心理变化,进而影响新生儿的正常生长发育,右美托咪定(dexmedetomidine,Dex)可以有效缓解抑郁情绪,降低产后抑郁症的发生。为探讨Dex对慢性应激抑郁妊娠大鼠子代发育及空间学习记忆能力的影响,将60只妊娠大鼠随机分为对照组、模型组、低剂量右美托咪定组和高剂量右美托咪定组,统计各组大鼠孕育率、平均产仔率和平均仔鼠成活率,并记录子代大鼠出生后体质量变化及学习记忆能力;检测子鼠脑组织乙酰胆碱(acetylcholine,Ach)、5-HT含量、TChE活力及海马组织CREB、p-CREB及BDNF的表达。结果显示,Dex可以以剂量依赖的方式提高慢性应激抑郁妊娠大鼠子代的平均成活率,调节脑组织Ach、5-HT、CREB、p-CREB和BDNF的水平,改善子鼠的学习记忆能力。结果表明,Dex可能通过调控神经递质和促进CREB信号传导,改善慢性应激抑郁妊娠大鼠的子代鼠学习记忆能力。研究探究了 Dex对妊娠期抑郁症大鼠子代生长发育和空间学习记忆能力的影响,以期指导临床治疗。     

Intrahippocampal Injections of Ghrelin and Aerobic Physical Exercise: Effects on Learning and Passive Avoidance Memory in Rats

Neurophysiology - Ghrelin, an endogenous ligand for the growth hormone secretagogue receptors, plays a considerable role in important neurological effects related to food intake and energy...     

老年大鼠学习记忆减退的神经基础

对由Ｍｏｒｒｉｓ水迷宫分得的青年、老年记忆正常和记忆减退鼠的脑组织分别进行突触、ＡＣｈＥ纤维、突触素、小白蛋白神经元以及突触体钙离子浓度、膜流动性的定量分析。结果表明老年记忆减退鼠新皮质、海马结构突触素含量、突触、胆碱能纤维、小白蛋白阳性神经元密度及突触体膜流动笥较老年记忆正常和青年鼠明显降低。老年记忆正常鼠与青年鼠各项均无显著差异。本研究提示各研究指标的异常与老年学习记忆减退密切相关。     

Treadmill Exercise Ameliorates Spatial Learning and Memory Deficits Through Improving the Clearance of Peripheral and Central Amyloid-Beta Levels

Aggregated amyloid beta (Aβ) peptides are believed to play a decisive role in the pathology of Alzheimer’s disease (AD). Previous evidence suggested that exercise contributes to the improvement of cognitive decline and slows down pathogenesis of AD; however, the exact mechanisms for this have not been fully understood. Here, we evaluated the effect of a 4-week moderate treadmill exercise on spatial memory via central and peripheral Aβ clearance mechanisms following developed AD-like neuropathology induced by intra-hippocampal Aβ_1–42 injection in male Wistar rats. We found Aβ_1–42-treated animals showed spatial learning and memory impairment which was accompanied by increased levels of amyloid plaque load and soluble Aβ_1–42 (sAβ_1–42), decreased mRNA and protein expression of neprilysin (NEP), insulin degrading enzyme (IDE) and low-density lipoprotein receptor-related protein-1 (LRP-1) in the hippocampus. Aβ_1–42-treated animals also exhibited a higher level of sAβ_1–42 and a lower level of soluble LRP-1 (sLRP-1) in plasma, as well as a decreased level of LRP-1 mRNA and protein content in the liver. However, exercise training improved the spatial learning and memory deficits, reduced both plaque load and sAβ_1–42 levels, and up-regulated expression of NEP, IDE, and LRP-1 in the hippocampus of Aβ_1–42-treated animals. Aβ_1–42-treated animals subjected to treadmill exercise also revealed decreased levels of sAβ_1–42 and increased levels of sLRP-1 in plasma, as well as increased levels of LRP-1 mRNA and protein in the liver. In conclusion, our findings suggest that exercise-induced improvement in both of central and peripheral Aβ clearance are likely involved in ameliorating spatial learning and memory deficits in an animal model of AD. Future studies need to determine their relative contribution.     

The Relationship Between Resource Control, Association with Females and Male Weapon Size in a Male Dominance Insect

In species with a resource‐defence (male dominance) mating system, males are expected to maximize fitness by controlling resources deemed more valuable by sexually receptive females because these sites attract more mates. Furthermore, males, which control more valuable resources should themselves be of high quality. I experimentally tested these predictions in the laboratory using the sexually dimorphic Wellington tree weta, Hemideina crassidens (Blanchard) (Orthoptera: Tettigonioidea: Anostostomatidae). Male H. crassidens use their mandibular weaponry to fight for control of harems (groups of adult females) that seek shelter in trees cavities (galleries). As predicted, larger galleries housed significantly larger groups of females and males with larger weaponry controlled large galleries significantly more often. Therefore, galleries with a larger volume are likely considered more valuable by males because they house larger harems. However, contrary to prediction, males with larger weaponry did not reside with significantly more females overall because females did not always form the largest possible groups in galleries and males with smaller weaponry were able to reside with single females in small galleries. The latter observation suggests a possible alternative mating strategy by disadvantaged males.     

The Effect of Severe Zinc Deficiency and Zinc Supplement on Spatial Learning and Memory

Zinc deficiency during pregnancy and during lactation has been shown to impair cognitive function and motor activity in offspring rats. In the present study, the effect of zinc deficiency and zinc supplement on spatial learning and memory in Morris Water Maze (MWM) and motor activity in open field were investigated. Pregnant rats after mating were divided to three groups. Control group fed a standard diet and a zinc deficient (ZnD) group fed a diet deficient in zinc (0.5–1.5 ppm) and a zinc supplement (ZnS) group fed a standard diet and enhanced zinc in the drinking water (10 ppm). All the diets were exposed during the last trisemester of pregnancy and during lactation. Rat’s offspring in these groups were tested for spatial learning and memory in MWM at post natal day (PND) 56 and were tested for motor activity in open field at PND 66.The Escape Latency (EL) and Traveled Distance (TD) in the ZnD group were increased but Percentage of Time Spent in the target quadrant (PTS) was decreased compared to the control group. In addition, these were no significant differences in EL and TD, but PTS had significant increase in ZnS compared to the control group. In the open field, Total Distance Moved (TDM) and Time of Motor Activity (TMA) for the ZnD were decreased compared to the control group, but there were no significant differences in TDM and TMA between control and ZnS groups. These findings suggest that zinc deficiency during the last trimester of pregnancy and during lactation impaired spatial learning and memory in their offsprings and has also negative effect on motor activity. In addition, ZnS has a significant effect on spatial learning and memory but no effect on motor activity in their offsprings.     

The Impact of Adult Vitamin D Deficiency on Behaviour and Brain Function in Male Sprague-Dawley Rats

Background

Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD) deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats.

Methods

Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT) and the 5 choice continuous performance task (5C-CPT) and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS) task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum.

Results

AVD-deficient rats were deficient in vitamin D₃ (<10 nM) and had normal calcium and phosphate levels after 8–10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI) than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA) responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum.

Conclusions

AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour.     

Epigallocatechin-3-Gallate Attenuates Impairment of Learning and Memory in Chronic Unpredictable Mild Stress-Treated Rats by Restoring Hippocampal Autophagic Flux

Epigallocatechin gallate (EGCG) is a major polyphenol in green tea with beneficial effects on the impairment in learning and memory. Autophagy is a cellular process that protects neurons from stressful conditions. The present study was designed to investigate whether EGCG can rescue chronic unpredictable mild stress (CUMS)-induced cognitive impairment in rats and whether its protective effect involves improvement of autophagic flux. As expected, our results showed that CUMS significantly impaired memory performance and inhibited autophagic flux as indicated by elevated LC3-II and p62 protein levels. At the same time, we observed an increased neuronal loss and activated mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6k) signaling in the CA1 regions. Interestingly, chronic treatment with EGCG (25 mg/kg, i.p.) significantly improved those behavioral alterations, attenuated histopathological abnormalities in hippocampal CA1 regions, reduced amyloid beta1–42 (Aβ₁₋₄₂) levels, and restored autophagic flux. However, blocking autophagic flux with chloroquine, an inhibitor of autophagic flux, reversed these effects of EGCG. Taken together, these findings suggest that the impaired autophagy in CA1 regions of CUMS rats may contribute to learning and memory impairment. Therefore, we conclude that EGCG attenuation of CUMS-induced learning and memory impairment may be through rescuing autophagic flux.