Crocin ameliorates neuroinflammation and cognitive impairment in mice with Alzheimer's disease by activating PI3K/AKT pathway.

BACKGROUND: Crocin has a good prospect in the treatment of Alzheimer's disease (AD), but the mechanisms underlying its neuroprotective effects remain elusive. This study aimed to investigate the neuroprotective effects of Crocin and its underlying mechanisms in AD. METHODS: AD mice were set up by injecting Aß25-35 solution into the hippocampus. Then, the AD mice were injected intraperitoneally with 40 mg/kg/day of Crocin for 14 days. Following the completion of Crocin treatment, an open-field test, Y-maze test and Morris water maze test were conducted to evaluate the impact of Crocin on spatial learning and memory deficiency in mice. The effects of Crocin on hippocampal neuron injury, proinflammatory cytokine expressions (IL-1ß, IL-6, and TNF-α), and PI3K/AKT signaling-related protein expressions were measured using hematoxylin and eosin staining, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) experiments, respectively. RESULTS: Crocin attenuated Aß25-35-induced spatial learning and memory deficiency and hippocampal neuron injury. Furthermore, the Western blot and qRT-PCR results showed that Crocin effectively suppressed inflammation and activated the PI3K/AKT pathway in Aß25-35-induced mice. CONCLUSION: Crocin restrained neuroinflammation via the activation of the PI3K/AKT pathway, thereby ameliorating the cognitive dysfunction of AD mice.

Maternal high fat diet programs spatial learning and central leptin signaling in mouse offspring in a sex-specific manner.

Environmental factors in early life have been demonstrated to increase the risk of neurodevelopmental disorders in offspring, especially the deficiency of the cognitive ability. Leptin has emerged as a key hormone that conveys information on energy stores, but there is growing appreciation that leptin signaling may also play an important role in neurodevelopment. The present study aimed to investigate whether maternal HFD exposure impairs the offspring learning and memory through the programming of central leptin system. We observed that hippocampus-dependent learning and memory were impaired in male but not female offspring from HFD-fed maternal ancestors (C57BL/6 mice), as assessed by novel object recognition and Morris water maze tests. Moreover, the chromatin immunoprecipitation results revealed the maternal HFD consumption led to the increasement in the binding of the histone marker H3K9me3 in male offspring, which mediates gene silencing in the leptin receptor promoter region. Furthermore, there was an increase in the expression of the histone methylase SUV39H1 in male but not female offspring, which regulates H3K9me3. Additionally, it has been observed that IL-6 and IL-1 also could lead to similar alternations when acting on cultured hippocampal neurons in vitro. Taken together, our data suggest that maternal HFD consumption influences male offspring hippocampal cognitive performance in a sex-specific manner, and central leptin signaling may serve as the cross-talk between maternal diet and cognitive impairment in offspring.

The microtubule-dynamin binding inhibitor peptide PHDP5 rescues spatial learning and memory deficits in Alzheimer's disease model mice.

Dynamin is a microtubule (MT) binding protein playing a key role in vesicle endocytosis. In a brain slice model, tau loaded in presynaptic terminals assembles MTs, thereby impairing vesicle endocytosis via depletion of cytosolic dynamin. The peptide PHDP5, derived from the pleckstrin homology domain of dynamin 1, inhibits dynamin-MT interaction and rescues endocytosis and synaptic transmission impaired by tau when co-loaded in presynaptic terminals. We tested whether in vivo administration of PHDP5 could rescue the learning/memory deficits observed in Alzheimer's disease (AD) model mice. A modified PHDP5 incorporating a cell-penetrating peptide (CPP) and a FITC fluorescent marker was delivered intranasally to Tau609 transgenic (Tg) and 3xTg-AD mice. FITC-positive puncta were observed in the hippocampus of mice infused with PHDP5 or scrambled (SPHDP5) peptide, but not in saline-infused controls. In the Morris water maze (MWM) test for spatial learning/memory, AD model mice treated with FITC-PHDP5-CPP showed prominent improvements in learning and memory, performing close to the level of saline-infused WT mice control. In contrast, mice treated with a scrambled construct (FITC-SPHDP5-CPP) showed no significant improvement. We conclude that PHDP5 can be a candidate for human AD therapy.

Teaching Zebrafish Development in a STEM-Based Science Camp for Middle School Students.

Zebrafish have been used as an education tool for students of all ages and can be used in many learning environments to teach different fields of science. In this study, we focus on the biology of zebrafish. We describe an educational program within a weeklong science camp for students between 12 and 14 years old. The methodology described is based on running annual science camps over an 11-year period. In these camps, students learnt about the developmental stages of zebrafish, as well as general zebrafish biology, husbandry, ecology, behavior, and reproduction. This article describes how to provide students and educators with an educational program to explore, discover, and contribute to the ever-evolving landscape of biological understanding through active and visual learning. We describe the methodology, the evaluation, revisions to our program over time, and future directions for expansion.

Lrp8 knockout mice fed a selenium-replete diet display subtle deficits in their spatial learning and memory function.

Selenium is an essential trace element that is delivered to the brain by the selenium transport protein selenoprotein P (SEPP1), primarily by binding to its receptor low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), at the blood-brain barrier. Selenium transport is required for several important brain functions, with transgenic deletion of either Sepp1 or Lrp8 resulting in severe neurological dysfunction and death in mice fed a selenium-deficient diet. Previous studies have reported that although feeding a standard chow diet can prevent these severe deficits, some motor coordination and cognitive dysfunction remain. Importantly, no single study has directly compared the motor and cognitive performance of the Sepp1 and Lrp8 knockout (KO) lines. Here, we report the results of a comprehensive parallel analysis of the motor and spatial learning and memory function of Sepp1 and Lrp8 knockout mice fed a standard mouse chow diet. Our results revealed that Sepp1 knockout mice raised on a selenium-replete diet displayed motor and cognitive function that was indistinguishable from their wild-type littermates. In contrast, we found that although Lrp8-knockout mice fed a selenium-replete diet had normal motor function, their spatial learning and memory showed subtle deficits. We also found that the deficit in baseline adult hippocampal neurogenesis exhibited by Lrp8-deficit mice could not be rescued by dietary selenium supplementation. Taken together, these findings further highlight the importance of selenium transport in maintaining healthy brain function. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Landmark use by ghost crab (Ocypode quadrata) during wayfinding in a complex maze.

Species of crab have been shown to spatially track and navigate to consequential locations through different processes, such as path integration and landmark orienting. Few investigations examine their ability to wayfind in complex environments, like mazes, with multiple intersections and how they may utilize specific features to benefit this process. Spatial learning potentially would lend a fitness advantage to animals living in complicated habitats, and ghost crab (Ocypode quadrata) is a semiterrestrial species that typically occupies extensive beach environments, which present many navigational challenges. Despite their potential, there are currently no studies that investigate forms of spatial cognition in these animals. To better diversify our knowledge of this trait, the current research exposed ghost crab to a maze with seven intersections. Animals were given multiple trials to learn the location of a reward destination to a specific criterion proficiency. In one condition several landmarks were distributed throughout the maze, and in another the environment was completely empty. Results showed that ghost crab in the landmark present group were able to learn the maze faster, they required significantly fewer trials to reach the learning criterion than those in the landmark absent group. However, only approximately half of the total sample met the learning criterion, indicating the maze was rather difficult. These findings are interpreted through theories of route learning that suggest animals may navigate by establishing landmark-turn associations. Such processes have implications for the cognitive ability of ghost crab, and spatial learning in this species may support the notion of convergent evolution for this trait.

Effects of moderate intensity training and lithium on spatial learning and memory in a rat model: The role of SIRT3 and PGC1-α expression levels and brain-derived neurotropic factor.

In this study we investigated the potential synergistic effects of moderate interval training (MIT) and lithium on spatial learning and memory. Forty-two male Wistar males were classified into six groups including I: Control, II: 10 mg/kg/day IP lithium (Li10), III: MIT, IV: Li10 + MIT, V: 40 mg/kg/day IP lithium (Li40), and VI: Li40 + MIT. Then, the rats underwent Morris Water Maze (MWM) test to assess their spatial memory and learning ability. Brain-derived neurotrophic factor (BDNF) density was measured by enzyme-linked immunosorbent assay (ELISA), and the expression of PGC1 and SIRT3 were assessed via qRT-PCR. The results show that MIT improves both memory and spatial learning; but lithium alone, does not cause this. Additionally, those exposed to a combination of exercise and lithium also had improved spatial learning and memory. Finally, we observed a positive role of BDNF protein, and PGC1 gene on the effects of exercise and lithium.

Stereotypical Hippocampal Clustering Predicts Navigational Success in Virtualized Real-World Environments.

Structural differences along the hippocampal long axis are believed to underlie meaningful functional differences. Yet, recent data-driven parcellations of the hippocampus subdivide the hippocampus into a 10-cluster map with anterior-medial, anterior-lateral, and posteroanterior-lateral, middle, and posterior components. We tested whether task and experience could modulate this clustering using a spatial learning experiment where male and female participants were trained to virtually navigate a novel neighborhood in a Google Street View-like environment. Participants were scanned while navigating routes early in training and after a 2 week training period. Using the 10-cluster map as the ideal template, we found that participants who eventually learn the neighborhood well have hippocampal cluster maps consistent with the ideal-even on their second day of learning-and their cluster mappings do not deviate over the 2 week training period. However, participants who eventually learn the neighborhood poorly begin with hippocampal cluster maps inconsistent with the ideal template, though their cluster mappings may become more stereotypical after the 2 week training. Interestingly this improvement seems to be route specific: after some early improvement, when a new route is navigated, participants' hippocampal maps revert back to less stereotypical organization. We conclude that hippocampal clustering is not dependent solely on anatomical structure and instead is driven by a combination of anatomy, task, and, importantly, experience. Nonetheless, while hippocampal clustering can change with experience, efficient navigation depends on functional hippocampal activity clustering in a stereotypical manner, highlighting optimal divisions of processing along the hippocampal anterior-posterior and medial-lateral axes.

Caloric Restriction Improves Spatial Learning Deficits in Tau Mice.

Background: Caloric restriction (CR) has been recognized for its benefits in delaying age-related diseases and extending lifespan. While its effects on amyloid pathology in Alzheimer's disease (AD) mouse models are well-documented, its effects on tauopathy, another hallmark of AD, are less explored. Objective: To assess the impact of a short-term 30% CR regimen on age-dependent spatial learning deficits and pathological features in a tauopathy mouse model. Methods: We subjected male PS19 tau P301S (hereafter PS19) and age-matched wildtype mice from two age cohorts (4.5 and 7.5 months old) to a 6-week 30% CR regimen. Spatial learning performance was assessed using the Barnes Maze test. Tau pathology, neuroinflammation, hippocampal cell proliferation, and neurogenesis were evaluated in the older cohort by immunohistochemical staining and RT-qPCR. Results: CR mitigated age-dependent spatial learning deficits in PS19 mice but exhibited limited effects on tau pathology and the associated neuroinflammation. Additionally, we found a decrease in hippocampal cell proliferation, predominantly of Iba1+ cells. Conclusions: Our findings reinforce the cognitive benefits conferred by CR despite its limited modulation of disease pathology. Given the pivotal role of microglia in tau-driven pathology, the observed reduction in Iba1+ cells under CR suggests potential therapeutic implications, particularly if CR would be introduced early in disease progression.

Decision-making processes in perceptual learning depend on effectors.

Visual perceptual learning is traditionally thought to arise in visual cortex. However, typical perceptual learning tasks also involve systematic mapping of visual information onto motor actions. Because the motor system contains both effector-specific and effector-unspecific representations, the question arises whether visual perceptual learning is effector-specific itself, or not. Here, we study this question in an orientation discrimination task. Subjects learn to indicate their choices either with joystick movements or with manual reaches. After training, we challenge them to perform the same task with eye movements. We dissect the decision-making process using the drift diffusion model. We find that learning effects on the rate of evidence accumulation depend on effectors, albeit not fully. This suggests that during perceptual learning, visual information is mapped onto effector-specific integrators. Overlap of the populations of neurons encoding motor plans for these effectors may explain partial generalization. Taken together, visual perceptual learning is not limited to visual cortex, but also affects sensorimotor mapping at the interface of visual processing and decision making.

The Active Place Avoidance (APA) Test, an Effective, Versatile and Repeatable Spatial Learning Task for Mice.

Hippocampus-dependent spatial learning in rodents has been tested using a variety of methods. These include the Morris water maze (MWM), Y-maze, and novel object location (NOL) tasks. More recently, the active place avoidance (APA) task has been developed as an alternative to these more traditional approaches. In the APA task, mice must use spatial cues placed around a rotating arena to avoid a stationary shock zone. Due to the multiple parameters that can be adjusted, the APA task has been demonstrated to be a very versatile approach. It lends itself to being used longitudinally and repeatedly for the same cohort of mice. Here, we provide a detailed protocol to successfully conduct the APA task. We also highlight alternative APA approaches that can be used to examine different components of spatial learning. We describe the data collection and analysis processes. Critical steps during the APA task are discussed to increase the likelihood of successfully conducting the test. The APA task has several advantages over more traditional spatial navigation tests. It is appropriate to use with aged mice or those with disease phenotypes such as Alzheimer's disease. The complexity of the task can be easily altered, allowing a wide range of mouse strains to be tested. Further, the APA task is suitable for testing animals that have undergone surgery or experimental interventions that may have affected motor or neural function, such as stroke or traumatic brain injury.

Positive modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors differentially alters spatial learning and memory in juvenile rats younger and older than three weeks.

Remarkable performance improvements occur at the end of the third postnatal week in rodents tested in various tasks that require navigation according to spatial context. While alterations in hippocampal function at least partially subserve this cognitive advancement, physiological explanations remain incomplete. Previously, we discovered that developmental modifications to hippocampal glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in juvenile rats was related to more mature spontaneous alternation behavior in a symmetrical Y-maze. Moreover, a positive allosteric modulator of AMPA receptors enabled immature rats to alternate at rates seen in older animals, suggesting an excitatory synaptic limitation to hippocampal maturation. We then validated the Barnes maze for juvenile rats in order to test the effects of positive AMPA receptor modulation on a goal-directed spatial memory task. Here we report the effects of the AMPA receptor modulator, CX614, on spatial learning and memory in the Barnes maze. Similar to our prior report, animals just over 3 weeks of age display substantial improvements in learning and memory performance parameters compared to animals just under 3 weeks of age. A moderate dose of CX614 enabled immature animals to move more directly to the goal location, but only after 1 day of training. This performance improvement was observed on the second day of training with drug delivery or during a memory probe trial performed without drug delivery after the second day of training. Higher doses created more search errors, especially in more mature animals. Overall, CX614 provided modest performance benefits for immature rats in a goal-directed spatial memory task.

Intracranial self-stimulation reverses impaired spatial learning and regulates serum microRNA levels in a streptozotocin-induced rat model of Alzheimer disease.

BACKGROUND: The assessment of deep brain stimulation (DBS) as a therapeutic alternative for treating Alzheimer disease (AD) is ongoing. We aimed to determine the effects of intracranial self-stimulation at the medial forebrain bundle (MFB-ICSS) on spatial memory, neurodegeneration, and serum expression of microRNAs (miRNAs) in a rat model of sporadic AD created by injection of streptozotocin. We hypothesized that MFB-ICSS would reverse the behavioural effects of streptozotocin and modulate hippocampal neuronal density and serum levels of the miRNAs. METHODS: We performed Morris water maze and light-dark transition tests. Levels of various proteins, specifically amyloid-ß precurser protein (APP), phosphorylated tau protein (pTAU), and sirtuin 1 (SIRT1), and neurodegeneration were analyzed by Western blot and Nissl staining, respectively. Serum miRNA expression was measured by reverse transcription polymerase chain reaction. RESULTS: Male rats that received streptozotocin had increased hippocampal levels of pTAU S202/T205, APP, and SIRT1 proteins; increased neurodegeneration in the CA1, dentate gyrus (DG), and dorsal tenia tecta; and worse performance in the Morris water maze task. No differences were observed in miRNAs, except for miR-181c and miR-let-7b. After MFB-ICSS, neuronal density in the CA1 and DG regions and levels of miR-181c in streptozotocin-treated and control rats were similar. Rats that received streptozotocin and underwent MFB-ICSS also showed lower levels of miR-let-7b and better spatial learning than rats that received streptozotocin without MFB-ICSS. LIMITATIONS: The reversal by MFB-ICSS of deficits induced by streptozotocin was fairly modest. CONCLUSION: Spatial memory performance, hippocampal neurodegeneration, and serum levels of miR-let-7b and miR-181c were affected by MFB-ICSS under AD-like conditions. Our results validate the MFB as a potential target for DBS and lend support to the use of specific miRNAs as promising biomarkers of the effectiveness of DBS in combatting AD-associated cognitive deficits.

Contribution of statistical learning in learning to read across languages.

Statistical Learning (SL) refers to human's ability to detect regularities from environment Kirkham, N. Z. (2002) & Saffran, J. R. (1996). There has been a growing interest in understanding how sensitivity to statistical regularities influences learning to read. The current study systematically examined whether and how non-linguistic SL, Chinese SL, and English SL contribute to Chinese and English word reading among native Chinese-speaking 4th, 6th and 8th graders who learn English as a second language (L2). Children showed above-chance learning across all SL tasks and across all grades. In addition, developmental improvements were shown across at least two of the three grade ranges on all SL tasks. In terms of the contribution of SL to reading, non-linguistic auditory SL (ASL), English visual SL (VSL), and Chinese ASL accounted for a significant amount of variance in English L2 word reading. Non-linguistic ASL, Chinese VSL, English VSL, and English ASL accounted for a significant amount of variance in Chinese word reading. Our results provide clear and novel evidence for cross-linguistic contribution from Chinese SL to English reading, and from English SL to Chinese reading, highlighting a bi-directional relationship between SL in one language and reading in another language.

Visual artificial grammar learning across 1 year in 7-year-olds and adults.

Acquiring sequential information is of utmost importance, for example, for language acquisition in children. Yet, the long-term storage of statistical learning in children is poorly understood. To address this question, 27 7-year-olds and 28 young adults completed four sessions of visual sequence learning (Year 1). From this sample, 16 7-year-olds and 20 young adults participated in another four equivalent sessions after a 12-month-delay (Year 2). The first three sessions of each year used Stimulus Set 1, and the last session used Stimulus Set 2 to investigate transfer effects. Each session consisted of alternating learning and test phases in a modified artificial grammar learning task. In Year 1, 7-year-olds and adults learned the regularities and showed transfer to Stimulus Set 2. Both groups retained their final performance level over the 1-year period. In Year 2, children and adults continued to improve with Stimulus Set 1 but did not show additional transfer gains. Adults overall outperformed children, but transfer effects were indistinguishable between both groups. The current results suggest that long-term memory traces are formed from repeated sequence learning that can be used to generalize sequence rules to new visual input. However, the current study did not provide evidence for a childhood advantage in learning and remembering sequence rules.

Developmental changes in the visual, haptic, and bimodal perception of geometric angles.

Geometrical knowledge is typically taught to children through a combination of vision and repetitive drawing (i.e. haptics), yet our understanding of how different spatial senses contribute to geometric perception during childhood is poor. Studies of line orientation suggest a dominant role of vision affecting the calibration of haptics during development; however, the associated multisensory interactions underpinning angle perception are unknown. Here we examined visual, haptic, and bimodal perception of angles across three age groups of children: 6 to 8 years, 8 to 10 years, and 10 to 12 years, with age categories also representing their class (grade) in primary school. All participants first learned an angular shape, presented dynamically, in one of three sensory tracing conditions: visual only, haptic only, or bimodal exploration. At test, which was visual only, participants selected a target angle from four possible alternatives with distractor angle sizes varying relative to the target angle size. We found a clear improvement in accuracy of angle perception with development for all learning modalities. Angle perception in the youngest group was equally poor (but above chance) for all modalities; however, for the two older child groups, visual learning was better than haptics. Haptic perception did not improve to the level of vision with age (even in a comparison adult group), and we found no specific benefit for bimodal learning over visual learning in any age group, including adults. Our results support a developmental increment in both spatial accuracy and precision in all modalities, which was greater in vision than in haptics, and are consistent with previous accounts of cross-sensory calibration in the perception of geometric forms.

Spatial transfer of object-based statistical learning.

A large number of recent studies have demonstrated that efficient attentional selection depends to a large extent on the ability to extract regularities present in the environment. Through statistical learning, attentional selection is facilitated by directing attention to locations in space that were relevant in the past while suppressing locations that previously were distracting. The current study shows that we are not only able to learn to prioritize locations in space but also locations within objects independent of space. Participants learned that within a specific object, particular locations within the object were more likely to contain relevant information than other locations. The current results show that this learned prioritization was bound to the object as the learned bias to prioritize a specific location within the object stayed in place even when the object moved to a completely different location in space. We conclude that in addition to spatial attention prioritization of locations in space, it is also possible to learn to prioritize relevant locations within specific objects. The current findings have implications for the inferred spatial priority map of attentional weights as this map cannot be strictly retinotopically organized.

The role of intraamygdaloid oxytocin in spatial learning and avoidance learning.

The goal of the present study is to investigate the role of intraamygdaloid oxytocin in learning-related mechanisms. Oxytocin is a neuropeptide which is involved in social bonding, trust, emotional responses and various social behaviors. By conducting passive avoidance and Morris water maze tests on male Wistar rats, the role of intraamygdaloid oxytocin in memory performance and learning was investigated. Oxytocin doses of 10 ng and 100 ng were injected into the central nucleus of the amygdala. Our results showed that 10 ng oxytocin significantly reduced the time required to locate the platform during the Morris water maze test while significantly increasing the latency time in the passive avoidance test. However, the 100 ng oxytocin experiment failed to produce a significant effect in either of the tests. Wistar rats pretreated with 20 ng oxytocin receptor antagonist (L-2540) were administered 10 ng of oxytocin into the central nucleus of the amygdala and were also subjected to the aforementioned tests to highlight the role of oxytocin receptors in spatial- and avoidance learning. Results suggest that oxytocin supports memory processing during both the passive avoidance and the Morris water maze tests. Oxytocin antagonists can however block the effects of oxytocin in both tests. The results substantiate that oxytocin uses oxytocin receptors to enhance memory and learning performance.

Functional connectivity interacts with visual perceptual learning for visual field recovery in chronic stroke.

A reciprocal relationship between perceptual learning and functional brain changes towards perceptual learning effectiveness has been demonstrated previously; however, the underlying neural correlates remain unclear. Further, visual perceptual learning (VPL) is implicated in visual field defect (VFD) recovery following chronic stroke. We investigated resting-state functional connectivity (RSFC) in the visual cortices associated with mean total deviation (MTD) scores for VPL-induced VFD recovery in chronic stroke. Patients with VFD due to chronic ischemic stroke in the visual cortex received 24 VPL training sessions over 2 months, which is a dual discrimination task of orientation and letters. At baseline and two months later, the RSFC in the ipsilesional, interhemispheric, and contralesional visual cortices and MTD scores in the affected hemi-field were assessed. Interhemispheric visual RSFC at baseline showed the strongest correlation with MTD scores post-2-month VPL training. Notably, only the subgroup with high baseline interhemispheric visual RSFC showed significant VFD improvement following the VPL training. The interactions between the interhemispheric visual RSFC at baseline and VPL led to improvement in MTD scores and largely influenced the degree of VFD recovery. The interhemispheric visual RSFC at baseline could be a promising brain biomarker for the effectiveness of VPL-induced VFD recovery.

Abdominal surgery under ketamine anesthesia during second trimester impairs hippocampal learning and memory of offspring by regulating dendrite spine remodeling in rats.

Recent evidence showed that general anesthesia produces long-term neurotoxicity and cognitive dysfunction. However, it remains unclear whether maternal non-obstetric surgery under ketamine anesthesia during second trimester causes cognitive impairment in offspring. The present study assigned pregnant rats into three groups: 1) normal control group receiving no anesthesia and no surgery, 2) ketamine group receiving ketamine anesthesia for 2 h on the 14th day of gestation but no surgery, and 3) surgery group receiving abdominal surgery under ketamine anesthesia on the 14th day of gestation. On postnatal day 1, the offspring rats in Ketamine group and surgery group were assigned to receive intra-peritoneal injection of Senegenin (15 mg/kg), once per day for consecutive 14 days. The offspring's spatial perception, anxiety-like behavior, and learning and memory were evaluated. Then the offspring's hippocampal tissues were collected. The offspring of the surgery group were impaired in the spatial perception in the cliff avoidance test and the spatial learning and memory in the Morris water maze test. Accordingly, the activity of histone deacetylases increased, the protein levels of NEDD9, BDNF, p-TrkB, Syn and PSD-95 decreased, and the density of dendritic spines reduced in the hippocampus of the offspring of the surgery group, and such effects were not seen in the offspring of the ketamine group, neither in the offspring of control group. Senegenin alleviated the learning and memory impairment, and increased the protein levels of NEDD9, BDNF, p-TrkB, Syn and PSD-95 and the density of dendritic spines in the offspring of the surgery group. ketamine anesthesia plus surgery during second trimester impairs hippocampus-dependent learning and memory, and the deficits could be rescued by treatment with Senegenin.