OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Shenting" (GV24) and "Baihui" (GV20) on mitochondrial autophagy in hippocampal neurons and silent information regulator sirtuin 1 (Sirt1)/forkhead box O3 (FOXO3)/PTEN-inducible kinase 1 (PINK1)/Parkin pathway in rats with learning-memory impairment after cerebral ischemia reperfusion injury. METHODS: A total of 35 male SD rats were randomly divided into a sham operation group (9 rats) and a modeling group (26 rats). In the modeling group, middle cerebral artery occlusion method was used to establish the middle cerebral artery ischemia-reperfusion (MCAO/R) model, and 18 rats of successful modeling were randomly divided into a model group and an EA group, 9 rats in each one. EA was applied at "Shenting" (GV24) and "Baihui" (GV20) in the EA group, 30 min a time, once a day for 14 days. After modeling and on 7th and 14th days of intervention, neurologic deficit score was observed; the learning-memory ability was detected by Morris water maze test; the morphology of neurons in CA1 area of hippocampus was detected by Nissl staining; the mitochondrial morphology was observed by transmission electron microscopy; the protein expression of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B), P62, Sitrt1, FOXO3, PINK1 and Parkin was detected by Western blot. RESULTS: After modeling, the neurologic deficit scores in the model group and the EA group were higher than that in the sham operation group (P<0.001); on 7th and 14th days of intervention, the neurologic deficit scores in the model group were higher than those in the sham operation group (P<0.001), the neurologic deficit scores in the EA group were lower than those in the model group (P<0.05, P<0.01). After modeling, the escape latency in the model group and the EA group was prolonged compared with that in the sham operation group (P<0.001); on 9th-13th days of intervention, the escape latency in the model group was prolonged compared with that in the sham operation group (P<0.001), the escape latency in the EA group was shortened compared with that in the model group (P<0.05, P<0.01, P<0.001). The number of crossing plateau in the model group was less than that in the sham operation group (P<0.001); the number of crossing plateau in the EA group was more than that in the model group (P<0.05). In the model group, in CA1 area of hippocampus, the number of neurons was less, with sparse arrangement, nuclear fixation, deep cytoplasmic staining, and reduction of Nissl substance; the morphology of mitochondrion was swollen, membrane structure was fragmented, and autophagic lysosomes were formed. Compared with the model group, in the EA group, in CA1 area of hippocampus, the number of neurons was increased, the number of cells of abnormal morphology was decreased, and the number of Nissl substance was increased; the morphology of mitochondrion was more intact and the number of autophagic lysosomes was increased. Compared with the sham operation group, in the model group, the protein expression of Beclin-1, FOXO3, PINK1, Parkin and the LC3BⅡ/Ⅰ ratio in hippocampus were increased (P<0.01, P<0.001), while the protein expression of P62 was decreased (P<0.05). Compared with the model group, in the EA group, the protein expression of Beclin-1, Sirt1, FOXO3, PINK1, Parkin and the LC3BⅡ/Ⅰratio in hippocampus were increased (P<0.001, P<0.01), while the protein expression of P62 was decreased (P<0.001). CONCLUSION EA at "Shenting" (GV24) and "Baihui" (GV20) can relieve the symptoms of neurological deficits and improve the learning-memory ability in MCAO/R rats, its mechanism may relate to the modulation of Sirt1/FOXO3/PINK1/Parkin pathway and the enhancement of mitochondrial autophagy.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Rats ; Forkhead Box Protein O3/genetics* ; Reperfusion Injury/metabolism* ; Ubiquitin-Protein Ligases/genetics* ; Brain Ischemia/complications* ; Mitochondria/genetics* ; Autophagy ; Protein Kinases/genetics* ; Sirtuin 1/genetics* ; Humans ; Memory Disorders/psychology* ; Signal Transduction

Moringa oleifera, widely utilized in Ayurvedic medicine, is recognized for its leaves, seeds, and velamen possessing traditional effects such as vātahara(wind alleviation), sirovirecaka(brain clearing), and hridya(mental nourishment). This study aims to identify the medicinal part of ■ in the Sārasvata ghee formulation as described in the Bower Manuscript, while investigating the ameliorative effects of different medicinal parts of M. oleifera on learning and memory deficits in mice and elucidating the underlying molecular mechanisms. A total of 144 male ICR mice were randomly assigned to the following groups: control, model(scopolamine hydrobromide, Sco, 2 mg·kg~(-1)), donepezil(donepezil hydrochloride, Don, 3 mg·kg~(-1)), M. oleifera leaf low-, medium-, and high-dose groups(0.5, 1, 2 g·kg~(-1)), M. oleifera seeds low-, medium-, and high-dose groups(0.25, 0.5, 1 g·kg~(-1)), and M. oleifera velamen low-, medium-, and high-dose groups(0.31, 0.62, 1.24 g·kg~(-1)). Learning and memory abilities were assessed using the passive avoidance test and Morris water maze. Nissl and HE staining were employed to examine histopathological changes in the hippocampus. Transcriptomics and targeted metabolomics were used to screen differential genes and metabolites, with MetaboAnalyst 6.0 and O2PLS methods applied to identify key disease-related targets and pathways. RESULTS:: demonstrated that M. oleifera leaf(1 g·kg~(-1)) significantly ameliorated Sco-induced learning and memory deficits, outperforming M. oleifera seeds(0.25 g·kg~(-1)) and M. oleifera velamen(1.24 g·kg~(-1)). This was evidenced by improved behavioral performance, reversal of neuronal damage, and reduced acetylcholinesterase(AChE) activity. Multi-omics analysis revealed that M. oleifera leaf upregulated Tuba1c gene expression through the synaptic vesicle cycle, enhancing glutamate(Glu), dopamine(DA), and acetylcholine(ACh) release via Tuba1c-Glu associations for neuroprotection. M. oleifera seeds targeted the dopaminergic synapse pathway, promoting memory consolidation through Drd2-ACh associations. M. oleifera velamen was associated with the cocaine addiction pathway, modulating dopamine metabolism via Adora2a-DOPAC, with limited relevance to learning and memory. In conclusion, M. oleifera leaf exhibits superior efficacy and mechanistic advantages over M. oleifera seeds and velamen, suggesting that the ■ in the Sārasvata ghee formulation is likely M. oleifera leaf, providing scientific evidence for its identification in ancient texts.
Animals ; Moringa oleifera/chemistry* ; Male ; Mice ; Seeds/chemistry* ; Plant Leaves/chemistry* ; Mice, Inbred ICR ; Memory Disorders/psychology* ; Transcriptome/drug effects* ; Memory/drug effects* ; Learning/drug effects* ; Metabolomics ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Maze Learning/drug effects*

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

Early-life stress (ES) leads to cognitive dysfunction in female adolescents, but the underlying neural mechanisms remain elusive. Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role in cognition and ES-related cognitive deficits in male rodents. In this study, we aimed to investigate whether and how nectins contribute to ES-induced cognitive dysfunction in female adolescents. Applying the well-established limited bedding and nesting material paradigm, we found that ES impairs recognition memory, suppresses prefrontal NECTIN1 and hippocampal NECTIN3 expression, and upregulates corticotropin-releasing hormone (Crh) and its receptor 1 (Crhr1) mRNA levels in the hippocampus of adolescent female mice. Genetic experiments revealed that the reduction of dorsal CA1 (dCA1) NECTIN3 mediates ES-induced object recognition memory deficits, as knocking down dCA1 NECTIN3 impaired animals' performance in the novel object recognition task, while overexpression of dCA1 NECTIN3 successfully reversed the ES-induced deficits. Notably, prefrontal NECTIN1 knockdown did not result in significant cognitive impairments. Furthermore, acute systemic administration of antalarmin, a CRHR1 antagonist, upregulated hippocampal NECTIN3 levels and rescued object and spatial memory deficits in stressed mice. Our findings underscore the critical role of dCA1 NECTIN3 in mediating ES-induced object recognition memory deficits in adolescent female mice, highlighting it as a potential therapeutic target for stress-related psychiatric disorders in women.
Animals ; Female ; Mice ; CA1 Region, Hippocampal/metabolism* ; Cell Adhesion Molecules/metabolism* ; CRF Receptor, Type 1/metabolism* ; Memory Disorders/etiology* ; Mice, Inbred C57BL ; Nectins/genetics* ; Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors* ; Recognition, Psychology/physiology* ; Stress, Psychological/complications*

Post-traumatic stress disorder (PTSD) is a psychiatric disorder caused by traumatic past experiences, rooted in the neurocircuits of fear memory formation. Memory processes include encoding, storing, and recalling to forgetting, suggesting the potential to erase fear memories through timely interventions. Conventional strategies such as medications or electroconvulsive therapy often fail to provide permanent relief and come with significant side-effects. This review explores how fear memory may be erased, particularly focusing on the mnemonic phases of reconsolidation and extinction. Reconsolidation strengthens memory, while extinction weakens it. Interfering with memory reconsolidation could diminish the fear response. Alternatively, the extinction of acquired memory could reduce the fear memory response. This review summarizes experimental animal models of PTSD, examines the nature and epidemiology of reconsolidation to extinction, and discusses current behavioral therapy aimed at transforming fear memories to treat PTSD. In sum, understanding how fear memory updates holds significant promise for PTSD treatment.
Fear/psychology* ; Extinction, Psychological/physiology* ; Animals ; Stress Disorders, Post-Traumatic/psychology* ; Humans ; Memory Consolidation/physiology* ; Memory/physiology*

BACKGROUND: Prenatal stress can cause neurobiological and behavioral defects in offspring; environmental factors play a crucial role in regulating the development of brain and behavioral; this study was designed to test and verify whether an enriched environment can repair learning and memory impairment in offspring rats induced by prenatal stress and to explore its mechanism involving the expression of insulin-like growth factor-2 (IGF-2) and activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus of the offspring. METHODS: Rats were selected to establish a chronic unpredictable mild stress (CUMS) model during pregnancy. Offspring were weaned on 21st day and housed under either standard or an enriched environment. The learning and memory ability were tested using Morris water maze and Y-maze. The expression of IGF-2 and Arc mRNA and protein were respectively measured by using RT-PCR and Western blotting. RESULTS: There was an elevation in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy. Maternal stress's offspring exposed to an enriched environment could decrease their plasma corticosterone level and improve their weight. The offspring of maternal stress during pregnancy exhibited abnormalities in Morris water maze and Y-maze, which were improved in an enriched environment. The expression of IGF-2, Arc mRNA, and protein in offspring of maternal stress during pregnancy was boosted and some relationships existed between these parameters after being exposed enriched environment. CONCLUSIONS The learning and memory impairment in offspring of prenatal stress can be rectified by the enriched environment, the mechanism of which is related to the decreasing plasma corticosterone and increasing hippocampal IGF-2 and Arc of offspring rats following maternal chronic stress during pregnancy.
Animals ; Cytoskeletal Proteins/metabolism* ; Female ; Gene Expression Regulation ; Hippocampus/metabolism* ; Insulin-Like Growth Factor II/metabolism* ; Learning ; Learning Disabilities/psychology* ; Male ; Memory Disorders/psychology* ; Nerve Tissue Proteins/metabolism* ; Pregnancy ; Prenatal Exposure Delayed Effects/psychology* ; Random Allocation ; Rats ; Rats, Wistar ; Social Environment ; Stress, Psychological/genetics*

Bacopa monnieri is a medicinal plant with a long history of use in Ayurveda, especially in the treatment of poor memory and cognitive deficits. In the present study, we hypothesized that Bacopa monnieri extract (BME) can improve memory via increased cell proliferation and neuroblast differentiation in the dentate gyrus. BME was administered to 7-week-old mice once a day for 4 weeks and a novel object recognition memory test was performed. Thereafter, the mice were euthanized followed by immunohistochemistry analysis for Ki67, doublecortin (DCX), and phosphorylated cAMP response element-binding protein (CREB), and western blot analysis of brain-derived neurotrophic factor (BDNF). BME-treated mice showed moderate increases in the exploration of new objects when compared with that of familiar objects, leading to a significant higher discrimination index compared with vehicle-treated mice. Ki67 and DCX immunohistochemistry showed a facilitation of cell proliferation and neuroblast differentiation following the administration of BME in the dentate gyrus. In addition, administration of BME significantly elevated the BDNF protein expression in the hippocampal dentate gyrus, and increased CREB phosphorylation in the dentate gyrus. These data suggest that BME improves novel object recognition by increasing the cell proliferation and neuroblast differentiation in the dentate gyrus, and this may be closely related to elevated levels of BDNF and CREB phosphorylation in the dentate gyrus.
Animals ; Bacopa* ; Blotting, Western ; Brain-Derived Neurotrophic Factor* ; Cell Proliferation* ; Cognition Disorders ; Cyclic AMP Response Element-Binding Protein* ; Dentate Gyrus* ; Discrimination (Psychology) ; Immunohistochemistry ; Memory ; Mice ; Neurogenesis ; Phosphorylation* ; Plants, Medicinal

PURPOSE: Adolescents who experienced the alcohol consumption have gradually increased. Adolescence is a critical period of the neural plasticity in the brain. Neural plasticity is mediated by neurotrophins and has an impact on cognitive function. Environmental enrichment ameliorates the cognitive function and increases neurotrophins. Thus, we investigated the neuroprotective effect of environmental enrichment on ethanol induced cognitive impairment in adolescent rats. METHODS: The ethanol groups and the controls groups were injected with ethanol (0.5g/kg) and phosphate buffered saline, respectively, through intraperitoneal from 28th day of birth for 11 days. The environmental enrichment groups were provided larger cages containing toys than the standard cage . Passive avoidance test and Y-maze test were performed to evaluate the spatial memory. RESULTS: Environmental enrichment+ethanol group showed higher alterations than the standard environment+ethanol group in Y-maze test (p<.05). In hippocampus, The environmental enrichment+ethanol group showed significantly higher level of the number of c-fos positive celsl and density of tropomyosin receptors kinase B receptor than the standard environment+ethanol group (p<.05). CONCLUSION: So, we suggested that the environmental enrichment played a role as a prophylaxis for prevention of memory impairment induced by ethanol exposure in adolescence.
Adolescent* ; Alcohol Drinking ; Animals ; Brain ; Cognition ; Cognition Disorders ; Critical Period (Psychology) ; Ethanol* ; Hippocampus ; Humans ; Memory ; Nerve Growth Factors ; Neuroprotective Agents ; Parturition ; Phosphotransferases ; Plastics ; Play and Playthings ; Rats* ; Spatial Memory ; Tropomyosin

OBJECTIVETo evaluate the psychological state of children with epilepsy and analyze its influencing factors.

METHODSThe Mental Health Scale for Child and Adolescent was used to survey 113 children with epilepsy and 114 normal children to evaluate and compare their psychological state. Questionnaires were used to investigate the general status of all subjects and the disease condition and treatment of children with epilepsy. The possible influencing factors for the psychological state of children with epilepsy were analyzed.

RESULTSThe mental health status of children with epilepsy was poorer than that of normal children in cognition, thinking, emotion, will-behavior, and personality traits (P<0.05). Multivariate logistic regression analysis showed that family education, family relations, seizure frequency, seizure duration, EEG epileptiform discharges in the last six months, and number of types of antiepileptic drugs were correlated with the psychological state of children with epilepsy.

CONCLUSIONSThere is a wider range of psychological health problems in children with epilepsy than in normal children. Poor family living environment, poor seizure control, and use of many antiepileptic drugs are the risk factors affecting the psychological state of children with epilepsy. Improving family living environment, controlling seizures, and monotherapy help to improve the psychological state of children with epilepsy.

Adolescent ; Child ; Epilepsy ; drug therapy ; psychology ; Female ; Humans ; Logistic Models ; Male ; Memory Disorders ; etiology

OBJECTIVETo explore the possible neurophysiologic mechanisms of propofol and N-methyl-D- aspartate (NMDA) receptor antagonist against learning-memory impairment of depressed rats without olfactory bulbs.

METHODSModels of depressed rats without olfactory bulbs were established. For the factorial design in analysis of variance, two intervention factors were included: electroconvulsive shock groups (with and without a course of electroconvulsive shock) and drug intervention groups [intraperotoneal (ip) injection of saline, NMDA receptor antagonist MK-801 and propofol. A total of 60 adult depressed rats without olfactory bulbs were randomly divided into 6 experimental groups (n=10 per group): ip injection of 5 ml saline; ip injection of 5 ml of 10 mg/kg MK-801; ip injection of 5 ml of 10 mg/kg MK-801 and a course of electroconvulsive shock; ip injection of 5 ml of 200 mg/kg propofol; ip injection of 5 ml of 200 mg/kg propofol and a course of electroconvulsive shock; and ip injection of 5 ml saline and a course of electroconvulsive shock. The learning-memory abilities of the rats was evaluated by the Morris water maze test. The content of glutamic acid in the hippocampus was detected by high-performance liquid chromatography. The expressions of p-AT8Ser202 in the hippocampus were determined by Western blot analysis.

RESULTSPropofol, MK-801 or electroconvulsive shock alone induced learning-memory impairment in depressed rats, as proven by extended evasive latency time and shortened space probe time. Glutamic acid content in the hippocampus of depressed rats was significantly up-regulated by electroconvulsive shock and down-regulated by propofol, but MK-801 had no significant effect on glutamic acid content. Levels of phosphorylated Tau protein p-AT8Ser202 in the hippocampus was up-regulated by electroconvulsive shock but was reduced by propofol and MK-801 alone. Propofol prevented learning-memory impairment and reduced glutamic acid content and p-AT8Ser202 levels induced by electroconvulsive shock.

CONCLUSIONElectroconvulsive shock might reduce learning-memory impairment caused by protein Tau hyperphosphorylation in depressed rats by down-regulating glutamate content.

Animals ; Depression ; psychology ; Dizocilpine Maleate ; pharmacology ; Electroshock ; Glutamic Acid ; analysis ; Learning Disorders ; prevention & control ; Male ; Memory Disorders ; prevention & control ; Phosphorylation ; Propofol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; tau Proteins ; metabolism