Memory Behavior Research Articles

The Effect of Fe Content on the Shape Memory Effect of Ni-Mn-Ga-Fe Shape Memory Alloy Microwires after Ordering Heat Treatment

The shape memory capabilities of Heusler alloy microwires with two different contents of Fe element instead of Ga element following step-by-step ordering heat treatment were explored based on the stoichiometric ratio of Ni2MnGa. The melt-drawing technique was used to create the polycrystalline microwires, and the two microwires had Fe atomic contents of 4.7 at.% and 5.5 at.%, respectively. The field emission scanning electron microscope was used to analyze the microwire’s surface condition as well as the microscopic tensile fracture morphology. Using an X-ray diffractometer, the microwires’ crystal structure was identified for phase analysis. Differential scanning calorimetry was used to examine the microwires’ behavior during martensitic transformation. Using a dynamic mechanical stretcher, the elongation and recovery rate of microwires’ one- and two-way shape memory behavior were examined. The findings demonstrated that the microwire phase structure, martensitic transformation behavior, and shape memory capabilities all displayed good properties after the heat treatment was ordered.

Programmable Truncated Cuboctahedral Origami Metastructures Actuated by Shape Memory Polymer Hinges

AbstractOver the past few decades, origami‐inspired structures have attracted great attention across various engineering fields due to their unique geometric and mechanical characteristics. Additionally, combining origami structures with active materials is employed to achieve programmable mechanical properties and self‐reconfigurability under external stimuli. In this work, a novel family of truncated cuboctahedral origami metastructures is proposed. These designs integrate shape memory polymers (SMPs) to actively achieve programmable mechanical properties and shape memory behavior. By utilizing SMPs for the creases and stiff materials for the panels, this approach enables deformation along the creases while enhancing the overall structural robustness. The mechanical properties and shape memory processes of these structures are investigated in detail. The proposed origami metastructures exhibit a negative Poisson's ratio and demonstrate excellent energy storage capabilities. Notably, their mechanical properties can be programmed by controlling both temperature and geometric parameters. More particularly, their Poisson's ratio can be tuned within a range of zero to −1. As a result, these truncated cuboctahedral origami metastructures hold significant potential for applications across various engineering domains, particularly in composite structures and active metamaterials.

Autism spectrum disorder-like behaviors induced by hyper-glutamatergic NMDA receptor signaling through hypo-serotonergic 5-HT1A receptor signaling in the prefrontal cortex in mice exposed to prenatal valproic acid.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by repetitive behaviors, social deficits, and cognitive impairments. Maternal use of valproic acid (VPA) during pregnancy is associated with an increased risk of ASD in offspring. The prevailing pathophysiological hypothesis for ASD involves excitation/inhibition (E/I) imbalances and serotonergic dysfunction. Here, we investigated the association between glutamatergic-serotonergic neuronal interactions and ASD-like behaviors in mice exposed to prenatal VPA. Prenatal VPA exposure induced excessive repetitive self-grooming behavior and impaired social behavior and object recognition memory in young adult period. Prenatal VPA mice showed hyper-glutamatergic function (increase in basal extracellular glutamate levels and CaMKII phosphorylation) and hypo-serotonergic function (decrease in 5-hydroxyindoleacetic acid and stimulation-induced serotonin [5-HT] release, but an increase in 5-HT transporter expression) in the prefrontal cortex. Treatment with a low-affinity NMDA receptor antagonist (memantine), a selective 5-HT reuptake inhibitor (fluoxetine), and a 5-HT1A receptor agonist (tandospirone) attenuated both the increase in CaMKII phosphorylation and ASD-like behavior of prenatal VPA mice. Opto-genetic activation of the serotonergic neuronal system attenuated impairments in social behavior and object recognition memory in prenatal VPA mice. WAY-100635-a 5-HT1A receptor antagonist-antagonized the effect of fluoxetine on impaired social behavior and object recognition memory. These results suggest that E/I imbalance and ASD-like behavior are associated with hypo-serotonergic receptor signaling through 5-HT1A receptors in prenatal VPA mice.

Emotional comorbidities in epilepsy result from seizure-induced corticosterone activity

People with epilepsy often have psychiatric comorbidities that can significantly impair their quality of life. We previously reported that repeated seizure activity persistently alters endocannabinoid (eCB) signaling in the amygdala which accounts for comorbid emotional dysregulation in rats, however, the mechanism by which these alterations in eCB signaling within the epileptic brain occur is unclear. Endocannabinoid signaling is influenced by corticosterone (CORT) to modulate cognitive and emotional processes and a hyperactive hypothalamic-pituitary-adrenal (HPA) axis occurs in both people with epilepsy and nonhuman animal models of epilepsy.We employed selective pharmacological tools and a variety of approaches including whole-cell patch-clamp electrophysiology, behavioural paradigms and biochemical assays in amygdala kindled adult male Long-Evans rats. We aimed to determine whether seizures induce hypersecretion of CORT and the role this plays in eCB system dysregulation, impaired fear memory, and anxiety-like behaviours associated with seizure activity.Plasma CORT levels were significantly and consistently elevated following seizures over the course of kindling. Pre-seizure administration with the CORT synthesis inhibitor metyrapone prevented this seizure-induced CORT increase, prevented amygdala anandamide downregulation, and synaptic alteration induced by seizure activity. Moreover, treatment with metyrapone or combined glucocorticoid receptor (GR)/mineralocorticoid receptor (MR) antagonists prior to each elicited seizure were equally effective in preventing chronically altered anxiety-like behaviour and fear memory responses.Inhibiting seizure-induced corticosterone synthesis, or directly blocking the effects of CORT at GR/MR prevents deleterious changes in emotional processing and could be a treatment option for emotional comorbidities in epilepsy.

Non-nutritive Sweetener Aspartame Disrupts Circadian Behavior and Causes Memory Impairment in Mice.

As a non-nutritive sweetener, aspartame is widely used in everyday life. However, its safety is highly controversial, especially its effects on neurobehavior. We evaluated the effects of chronic daily oral administration of aspartame-containing drinking water (at doses equivalent to 7-28% of the FDA-recommended human DIV) on memory and rhythm behaviors in mice and further investigated changes at the molecular level in the brains. Our results demonstrated that mice exposed to aspartame exhibited memory impairment. Disorders of hippocampal neurotransmitter metabolism and pathological damage may be responsible for the aspartame-induced memory impairment via inhibition of the BDNF/TrkB pathway. Furthermore, our findings suggested that disturbed clock gene expression in the hypothalamus after aspartame exposure led to altered rest-activity behavior, and this disruption of the circadian rhythm may exacerbate memory impairment. This study highlights the negative neurobehavioral effects of aspartame and provides valuable insights into its rational and safe use.

Microscopic Origin of Polarity-Dependent VTH Shift in Amorphous Chalcogenides for 3D Self-Selecting Memory.

Ovonic threshold switching (OTS) selectors based on amorphous chalcogenides can revolutionize 3D memory technology owing to their self-selecting memory (SSM) behavior. However, the complex mechanism governing the memory writing operation limits compositional and device optimization. This study investigates the mechanism behind the polarity-dependent threshold voltage shift (ΔVTH) through theoretical and experimental analyses. By examining the physical principles of threshold switching and conducting defect state analysis, the ΔVTH as a memory window is confirmed to be attributed to the dynamics of charged defects and their gradient near electrodes, influenced by the nonuniform electric field after threshold switching. This study provides critical insights into the operational mechanism of OTS-based SSM, known as selector-only memory, highlighting its advantages for developing high-density, low-cost, and energy-efficient memory technologies in the artificial intelligence era.

Automated Robustness Verification of Concurrent Data Structure Libraries against Relaxed Memory Models

Clients reason about the behavior of concurrent data structure libraries such as sets, queues, or stacks using specifications that capture well-understood correctness conditions, such as linearizability. The implementation of these libraries, however, focused as they are on performance, may additionally exploit relaxed memory behavior allowed by the language or underlying hardware that weaken the strong ordering and visibility constraints on shared-memory accesses that would otherwise be imposed by a sequentially consistent (SC) memory model. As an alternative to developing new specification and verification mechanisms for reasoning about libraries under relaxed memory model, we instead consider the orthogonal problem of library robustness , a property that holds when all possible behaviors of a library implementation under relaxed memory model are also possible under SC. In this paper, we develop a new automated technique for verifying robustness of library implementations in the context of a C11-style memory model. This task is challenging because a most-general client may invoke an unbounded number of concurrently executing library operations that can manipulate an unbounded number of shared locations. We establish a novel inductive technique for verifying library robustness that leverages prior work on the robustness problem for the C11 memory model based on the search for a non-robustness witness under SC executions. We crucially rely on the fact that this search is carried out over SC executions, and use high-level SC specifications (including linearizability) of the library to verify the absence of a non-robustness witness. Our technique is compositional - we show how we can safely preserve robustness of multiple interacting library implementations and clients using additional SC fences to guarantee robustness of entire executions. Experimental results on a number of complex realistic library implementations demonstrate the feasibility of our approach.

A Low-Level Look at A-Normal Form

A-normal form (ANF) is a widely studied intermediate form in which local control and data flow is made explicit in syntax, and a normal form in which many programs with equivalent control-flow graphs have a single normal syntactic representation. However, ANF is difficult to implement effectively and, as we formalize, difficult to extend with new lexically scoped constructs such as scoped region-based allocation. The problem, as has often been observed, is that normalization of commuting conversions is hard. This traditional view of ANF that normalizing commuting conversions is hard, found in formal models and informed by high-level calculi, is wrong. By studying the low-level intensional aspects of ANF, we can derive a normal form in which normalizing commuting conversion is easy, does not require join points, or code duplication, or renormalization after inlining, and is easily extended with new lexically scoped effects. We formalize the connection between ANF and monadic form and their intensional properties, derive an imperative ANF, and design a compiler pipeline from an untyped -calculus with scoped regions, to monadic form, to a low-level imperative monadic form in which A-normalization is trivial and safe for regions. We prove that any such compiler preserves, or optimizes, stack and memory behaviour compared to ANF. Our formalization reconstructs and systematizes pragmatic choices found in practice, including current production-ready compilers. The main take-away from this work is that, in general, monadic form should be preferred over ANF, and A-normalization should only be done in a low-level imperative intermediate form. This maximizes the advantages of each form, and avoids all the standard problems with ANF.

Shape memory and shape recovery characterization of thermoplastic urethane

ABSTRACT Polyurethane shape memory polymer, as a smart material, has been becoming more and more popular due to its greater multifunctionality in various industrial and biomedical applications. Here, the authors reported the characterization, and comprehensive methodology and acquired the results of thermoplastic urethane (SMTPU) as a shape memory polymer, with 35°C as the glass transition temperature, by examining its creep. This smart polymer exhibits excellent shape memory behaviour due to its steady, chemically cross-linked network. Such behaviour of shape memory polymer determines its usability in various functional applications. Furthermore, the activation temperature range of SMPTPU is close to body temperature and room temperature as well, so it can be employed in more demanding industrial applications. Thus, it becomes essential to investigate the shape-changing/memory behaviour of commercial SMTPU. A quantitative analysis was done to determine the effects of programming temperature, maximum uniaxial strain, and compressive strain on shape memory characteristics viz. the shape recovery ratios and shape fixity ratios. Along with the excellent shape memory effect, this material also exhibits high creep and elasticity at room temperature, indicating that it may be used for various industrial and biomedical applications.

12539 Estrogen Type In Contraceptives Matters: Effects On Spatial Memory And Anxiety-Like Behaviors In A Female Rat Model

Abstract Disclosure: A.P. Hegwood: None. S. Kujawa: None. A.V. Prakapenka: None. According to U.S. Centers for Disease Control & Prevention, ∼12% of the U.S. population uses combined oral contraceptives (COCs). Behavioral side effects are common factors in COC discontinuation. Management of COC-related side effects primarily centers around altering the synthetic ethinyl estradiol (EE) dose, the predominant estrogen in COCs. Estradiol valerate (EV) is a recently introduced natural estrogen alternative to EE. EE-containing COCs, such as EE/dienogest (DNG), were found to decrease free steroid hormone serum levels compared to EV-containing COCs, such as EV/DNG. In women and in female rodent models, steroid hormones (e.g., 17-ß estradiol (E2), testosterone) dose-dependently modulate spatial memory and anxiety-related behaviors. We hypothesized that in a rat model of hormonal contraceptive use, EE/DNG differentially modulates spatial memory and anxiety-like behaviors compared to EV/DNG, corresponding to circulating steroid hormone levels. Thirty-six young-adult (3-4-months-old) female rats were randomly assigned to EE/DNG (0.13µg EE and 8.6µg DNG per day), EV/DNG (8.6µg EV and 8.6µg DNG per day), or vehicle treatment (propylene glycol) continuously administered by subcutaneous osmotic pump. At four weeks of treatment, rats were tested on the delayed spontaneous alternation (dSA) task to evaluate spatial memory and the elevated plus maze (EPM) to evaluate anxiety-like behavior. Following EPM, serum was collected and analyzed for E2, progesterone, androstenedione, and testosterone levels using liquid chromatography-mass spectrometry and corticosterone levels using radioimmunoassay. Spontaneous alternation behaviors were similar across all three groups on the dSA. However, EE/DNG increased use of an egocentric navigational strategy, the use of consecutive turns, on the dSA compared to vehicle and EV/DNG. Egocentric strategy is likely mediated by the striatal memory system, engagement of which is elevated with stress and anxiety. Of note, EE/DNG decreased time spent in the open arms of the EPM compared to vehicle and EV/DNG, indicating increased anxiety-like behaviors with EE/DNG. Both EE/DNG and EV/DNG decreased androstenedione, testosterone, and E2 circulating levels compared to vehicle. Steroid hormone serum levels did not differ between EE/DNG and EV/DNG; 58% of EE/DNG serum samples were undetermined/below threshold for E2 levels, limiting statistical analysis. Altogether, we found that, compared to vehicle and the natural EV, the synthetic EE component in hormonal contraceptives elevates anxiety-like behaviors in female rats, an effect that corresponds to increased use of an egocentric navigational strategy on a spatial memory task. Our findings support the notion that estrogen type matters for behavioral outcomes associated with contraceptive use, identifying estrogen type as a possible tool for management of COC-related side effects. Presentation: 6/1/2024

GC/MS and LC-ESI-MS analysis of Conocarpus erectus Leaves Extract via Regulating Amyloid-β-peptide, Tau protein, Neurotransmitters, Inflammation and Oxidative Stress against AlCl3-Induced Alzheimer's Disease in Rats.

This study investigated the therapeutic effect of Conocarpus erectus leaves methanolic extract against AlCl3 -induced Alzheimer's disease (AD) in rats comparing with Donepezil-hydrochloride as a reference drug. The bioactive compounds of C. erectus leaves were isolated and identified by GC/MS and LC-ESI-MS analysis. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), amyloid-β-peptide (Aβ-peptide), tau protein, acetylcholinesterase (AChE), serotonin (5-HT), dopamine (DA) and nor-adrenaline (NE) levels were estimated. The neuromuscular strength, memory behavior and histopathological examination of cerebral cortex region were also conducted. Forty-three compounds were characterized from the non-polar fraction of C. erectus L. leaves extract and nineteen compounds were identified from the defatted extract. AlCl3- induction caused significant elevation of brain oxidative stress, Aβ-peptide, tau protein, IL-6, TNF-α and AChE levels. A significant decrease in 5-HT, ND and DA levels were noticed. Additionally, AlCl3 reduced neuromuscular strength and compromised memory function. Treatment of AlCl3- induced rats with C. erectuse extract ameliorated these selected parameters by variable degrees. In conclusion, C. erectus protects against AlCl3- induced AD in rats through its antioxidant, anti-inflammatory, and antineutron damage. It could be considered as a new nutraceutical agent for attenuating symptoms associated with Alzheimer's disease.

Neuroprotective impact of glycitin on memory impairment in a pentylenetetrazol-induced chronic epileptic rat model: insights into hippocampal histology, oxidative stress, and inflammation.

Epilepsy, characterized by recurrent seizures, often accompanies neurocognitive impairments and is associated with increased oxidative stress and inflammation. This study investigates the possible neuroprotective properties of glycitin, a soy isoflavone, on memory impairment, its impact on oxidative stress responses, and inflammatory gene expression in a chronic epileptic rat model induced by pentylenetetrazol (PTZ). Glycitin was administered at varying doses to evaluate its potential neuroprotective impact on memory, oxidative stress, and inflammation in this model. Behavioural assessments, memory retention and recall capabilities, histopathological examinations, measurements of oxidative stress biomarkers, and molecular assessments were employed for comprehensive evaluation. The results demonstrated that glycitin significantly improved memory impairment and reduced oxidative stress in epileptic rats. Additionally, glycitin treatment decreased the expression of tumor necrosis factor-α (TNF-α) and nuclear factor kappa B (NF-κB), indicating its potential to modulate the inflammatory response associated with epilepsy. These observations underscore the potential of glycitin as a therapeutic candidate for mitigating memory impairments linked to chronic epilepsy due to its antioxidant and anti-inflammatory properties, offering insights into novel avenues for the development of targeted interventions aimed at preserving cognitive function and ameliorating oxidative damage and inflammation in epileptic conditions.

Shape Memory Polymer Bioglass Composite Scaffolds Designed to Heal Complex Bone Defects.

An off-the-shelf scaffold with requisite properties could enable the viable treatment of irregular craniomaxillofacial bone defects. Notably, the scaffold should be conformally fitting, innately bioactive, and bioresorbable. In prior work, we developed a series of shape memory polymer (SMP) scaffolds based on cross-linked poly(ε-caprolactone) (PCL). These were capable of "self-fitting" into complex bone defects when exposed to temperatures above the melt transition of the constituent PCL, either linear-PCL-diacrylate (linear-PCL-DA, Tm ∼55 °C) or star-PCL-tetraacrylate (star-PCL-TA, Tm ∼45 °C) for the potential to improve tissue safety. To achieve favorably increased degradation rates versus PCL-only scaffolds, semi-interpenetrating networks (semi-IPNs) were formed by including linear- or star-poly(l-lactic acid) (PLLA). A potential limitation of these self-fitting scaffolds is the lack of bioactivity, which is essential to osteoinductivity and osseointegration. Herein, analogous composite scaffolds were formed with 45S5 bioglass (BG) to impart bioactivity. The solvent-cast particulate leaching fabrication method was adapted to introduce BG to the fused salt template, resulting in composites with BG concentrated on the pore wall surfaces rather than within pore struts. Composite scaffolds with good pore wall integrity were produced with 2.5, 5, and 10 wt % BG. All composite scaffolds exhibited non-brittle behavior and did not fracture with 85% strain. For semi-IPN composite scaffolds, PLLA crystallinity was lost, and mechanical properties were not appreciably altered versus the non-BG controls. Sufficient retention of PCL crystallinity led to excellent shape memory behavior. The inclusion of 5 and 10 wt % BG led to hydroxyapatite mineralization after 1 day of exposure to simulated body fluid, as well as increased rates of in vitro degradation.

Ameliorative effects of aqueous extract of Colocasia esculenta leaf against lipopolysaccharide-induced prefrontal cortex damage in mice

IntroductionThe prefrontal cortex (PFC), crucial for cognition and memory, occupies a third of the cerebral cortex. This study investigated the protective effects of aqueous extract of Colocasia esculenta leaf (AECEL) against lipopolysaccharide (LPS)-induced PFC damage in mice.Methods42 male Swiss albino mice (18–22 g) were divided into six groups. Group A: healthy controls. Groups B-F received daily intraperitoneal LPS injections (0.5 mg/kg) for seven days. Group B: received distilled water, (2 ml) subsequently. Groups C-E: AECEL at 400, 600, and 800 mg/kg, respectively. Group F: donepezil (DPZ, 2.5 mg/kg) by oral gavage. All treatments continued for 28 days.ResultsLPS exposure significantly increased brain oxidative stress markers and reduced antioxidant enzymes compared to controls (p < 0.05). AECEL and DPZ administration significantly reduced brain oxidative stress markers and reduced antioxidant enzymes, as well as tumor necrosis factor-α and interleukin-6 levels (p < 0.05) compared to LPS ONLY group. Y-maze testing revealed decreased alternation (%) in the LPS group compared to controls (p < 0.05). Based on Y-maze performance, AECEL at 400 mg/kg emerged as the most effective dose, significantly improving alternation (%) compared to both LPS and LPS + DPZ groups (p < 0.05). Bielschowsky staining showed senile plaques and neurofibrillary tangles in the LPS group.ConclusionLPS induced PFC damage. Among the tested doses, AECEL at 600 mg/kg demonstrated the most effective improvement in cognitive function, memory, and anxiety-like behaviors as measured by the Y-maze test.

Behavioral Assays for Comprehensive Evaluation of Cognitive and Neuropsychiatric Comorbidities of Traumatic Brain Injury and Chronic Neurological Disorders.

Neurological deficits, psychiatric disorders, and cognitive impairments often accompany stroke, brain injury, epilepsy, and many neurological disorders, which present intricate comorbidities that challenge recognition and management. There are many tools and paradigms for evaluating learning, memory, anxiety, and depression-like behaviors in lab animal models of brain disorders. However, there is a significant gap between clinical observations and experimental models, which limit understanding of the complex interplay between chronic brain conditions and their impact on cognitive dysfunction and psychiatric impairments. This article describes an overview of experimental rationale, methods, protocols, and strategies for evaluating sensorimotor, affective and cognitive-associated comorbid behaviors in epilepsy, traumatic brain injury (TBI), stroke, spinal cord injury (SCI), and many other neurological disorders. First, we delve into clinical evidence elucidating the profound impact of comorbidities, e.g., psychiatric disorders and cognitive deficits, in individuals with epilepsy. Then, we discuss diverse approaches to assess these comorbidities in experimental models of brain diseases. Finally, we explore the methodologies for assessing motor function, sensorimotor, behavior, and psychiatric health. We cover strategies and protocols enabling these assays, including implementing behavioral paradigms to assess learning and memory, anxiety, and depression-like behaviors in rodents in health and disease conditions. It is essential to consider a comprehensive battery of tests to investigate various behavioral deficits, considering environment, age, and sex differences relevant to the disease, such as TBI, SCI, epilepsy, stroke, and other complex neurological conditions. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC.

Isolating financial cycles using the fractional cyclical model in selected economies: 1970–2019

We attempt in this paper to identify financial cycles in 43 countries using data from 1970 to 2019. We use a model based on stochastic cycles that employ fractional integration. The results indicate that the average duration of the cycles is 23 years for Denmark, India, South Korea, Sweden, Spain, Switzerland, and the United States. Our study contributes to the field of research by proposing an alternative model and method for researching financial cycles. The advantage of using such an approach is the ability to isolate more robust stochastic cycles allowing for the possibility of the existence of multiple financial cycles in financial data. It is also found that the credit-GDP ratio exhibits long memory and persistent behavior at the long run frequency. Long memory is found in a number of countries at the cyclical structure with shock of the dynamics of the financial cycle lasting long before disappearing in some of the countries examined.

Fasudil attenuates lipopolysaccharide-induced cognitive impairment in C57BL/6 mice through anti-oxidative and anti-inflammatory effects: Possible role of aquaporin-4

IntroductionProcesses that generate systemic inflammation are strongly associated with neurodegenerative diseases. This study aimed to explore the potential anti-oxidative and anti-inflammatory effects of fasudil and its role in modulating aquaporin-4 (AQP-4) to improve cognitive impairment in a systemic inflammation model induced by lipopolysaccharide (LPS). Methodfourty C57BL/6 mice were assigned to four groups, including sham, LPS, sham+fasudil, and LPS+fasudil). Intraperitoneal LPS was given (500μg/kg/day) at hours 0, 24, 48, and 72, and fasudil (30mg/kg) administered intraperitoneal injections 2hours after LPS injection. The open field, Y-maze, and Novel object tasks was used to assess learning and memory. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in the hippocampus also measured as markers of oxidative stress and inflammation. Furthermore, the expression of AQP-4 measured in the intact and experimental groups. ResultsThe results showed that Fasudil significantly improved memory and anxiety behavior induced by LPS in the open field maze, spatial recognition memory in the Y-maze, and performance in the novel object recognition task. It also mitigates hippocampal MDA and SOD levels. Additionally, fasudil ameliorated LPS-induced hippocampal levels of TNFα and IL-10 and increased hippocampal levels of AQP-4 expression in mice. ConclusionOur results suggest that fasudil in the LPS model of systemic inflammation could improve cognition by suppressing oxidative stress and inflammation and increasing AQP-4 protein expression. These findings highlighted the potential of fasudil as a neuroprotective agent. However, further research is required to fully understand its neuroprotective properties in the treatment of neurodegenerative disorders.

Dihydroquercetin nanoparticles nasal gel is a promising formulation for amelioration of Alzheimer’s disease

Dihydroquercetin is a natural flavonoid with anti-inflammatory, antioxidant, and neuroprotective activities. Dihydroquercetin exhibits a great neuroprotector promise in Alzheimer’s disorder via preventing the aggregation of amyloid-beta-peptide-Aβ(1–42). The goal of the study was to create dihydroquercetin-loaded-chitosan nanoparticles (DHQ-CS NPs) loaded to a mucoadhesive, thermosensitive in-situ gel for direct nasal administration to cure Alzheimer’s disorder. Loading drug in chitosan nanoparticles and incorporation into thermosensitive gel enhanced residence time and reduced mucociliary-clearance. Different in-vitro-physicochemical-characteristics of gels and nanoparticles-characterization were used to evaluate the formulations. The therapeutic effectiveness of DHQ-CS NPs gel was evaluated behaviorally, biochemically and histopathologically in Alzheimer’s-rat-model compared to intranasal DHQ gel. The small particles-size was obtained = 235.3 nm of DHQ-CS NPs. The DHQ-CS NPs gel demonstrated a greater release rate compared to the raw DHQ gel. Additionally, the nasal-administration of the DHQ-CS NPs gel showed better In-vivo results compared to DHQ gel, through improvement of memory and learning deficits and also the exploratory behavior and new object memory in streptozotocin induced-Alzheimer rats. Biochemically, the intranasal DHQ-CS NPs gel, showed reduced both Aβ-protein formation and tau protein hyperphosphorylation, inhibition of acetylcholine esterase activity and oxidative stress in the brain with increase of total antioxidants in the brain and serum, compared to DHQ gel. Histopathologically, the DHQ-CS NPs nasal gel produced improvement in the hippocampal and cerebral cortex structures, being comparable to the normal group. Consequently, the intranasal DHQ-CS NPs loaded in-situ gel seems to be a promising therapeutic formulation for Alzheimer’s disease medication.

Particulate matter induced cognitive impairments via endoplasmic reticulum stress-mediated damage to mitochondria-associated endoplasmic reticulum membranes in immature rats

Particulate matter (PM) exposure has been increasingly recognized as detrimental to cognitive function and is associated with neurodevelopmental disorders. Mitochondria-associated endoplasmic reticulum membranes (MAMs) form an integrated interface between mitochondria and the endoplasmic reticulum (ER), facilitating crucial cellular functions. Prolonged ER stress (ERS) is implicated in various pathological states in the nervous system. MAMs and ERS may play vital roles in adverse effects of early-life PM exposure on cognitive abilities. This study investigated whether ERS plays a role in PM-induced MAMs dysfunction, leading to neuronal damage and cognitive impairments in early postnatal rats. Using a rat model with PM exposure concentrations of 2 and 10 mg/kg from postnatal Day 3 (PND3) to PND28, we observed that PM exposure resulted in anxiety-like behavior and impaired spatial working memory. The protein levels of ERS markers, including GRP78 and CHOP, were significantly increased in response to PM exposure. Western blot, transmission electron microscopy (TEM), and immunofluorescence analyses revealed decreased MAMs-related proteins and disrupted MAM structure and function caused by PM exposure. Administration of the ERS inhibitor 4-phenylbutyric acid (4-PBA) ameliorated these effects, restoring MAMs integrity and improving cognitive deficits. These findings highlighted the key role of ERS-MAMs dysfunction in PM-induced neurotoxicity and cognitive impairments, providing a new perspective and strategy for the prevention of cognitive deficits in early age with PM exposure.

Synaptophysin and GSK-3beta activity in the prefrontal cortex may underlie the effects of REM sleep deprivation and lithium on behavioral functions and memory performance in male rats

Rapid-eye movement (REM) stage of sleep serves a critical role in processing cognitive and behavioral functions. Evidence shows that REM sleep deprivation (REM SD) strongly affects the mood state and cognitive abilities. However, there are many inconsistent reports. Although the exact molecular mechanisms underlying REM SD effects have not well been discovered, however, molecular factors including those affected synaptic plasticity and mood state may be involved. There are two important molecular factors that have not been well studied: synaptophysin and glycogen synthase kinase-3 beta (GSK-3beta). The present study aimed to investigate the role of synaptophysin and GSK-3beta in the modulation of memory and behavioral changes induced by REM SD and lithium (as a potent GSK-3beta inhibitor and mood stabilizer). Multiple platform apparatus was used to induce REM SD for 48 h. Lithium was injected at the dose of 50 mg/kg, intraperitoneal (i.p.). Locomotor activity, anxiety-like behavior, pain threshold, novel object recognition memory, and synaptophysin and GSK-3beta level in the prefrontal cortex were evaluated. Results showed REM SD increased locomotor activity, decreased pain threshold, impaired novel object recognition memory, decreased synaptophysin and increased GSK-3beta levels. Lithium reversed these effects. Anxiety-like behavior was unaffected. For the first time, the present study showed that GSK-3beta and synaptophysin may be involved in the modulation of behavior and cognition induced by REM SD and lithium. In conclusion, we suggested that GSK-3beta upregulation and synaptophysin downregulation may underlie the deleterious effects of REM SD, while lithium may counteract REM SD effects via restoring the level of both.