Elevated Stress Levels Research Articles

The Relationship Between Perceived Stress and Aggression Behavior Among Individuals with Major Depressive Disorder (MDD)

This study examines how perceived stress impacts aggression in individuals diagnosed with Major Depressive Disorder (MDD), specifically looking at the variations between genders. The study utilizes a quantitative questionnaire to investigate the correlation between stress and aggression, as well as the factors that exacerbate this relationship, including the reciprocal linking of stress and aggression. Perceived stress and aggression exhibited a substantial and advantageous correlation (r = 0.62, p < 0.01), suggesting that an increase in aggression was linked to elevated stress levels. 78% of males and 58% of females admitted to frequently exhibiting aggression, while males reported engaging in aggressive behaviors more frequently than females. A reciprocal relationship was discovered, in which escalated aggression led to elevated stress levels and increased stress caused heightened aggression (r = 0.54, p < 0.05), thereby establishing a detrimental feedback cycle. These results indicate that interventions aimed at reducing stress could be especially helpful in decreasing aggression in male MDD patients. This study enhances our comprehension of the dynamics between stress and aggression in MDD and highlights the significance of addressing these aspects in therapy.

OVERLOADING IN ELEMENTARY SCHOOL TEACHERS: A REVIEW

Teacher workload intensification in basic education is a critical issue impacting both teacher well-being and the quality of education. This literature review employs a systematic review methodology to synthesize findings from existing research on the causes and consequences of excessive workloads among teachers. The review identifies key contributors to workload intensification, including administrative responsibilities, lesson planning, student assessments, extracurricular duties, and broad curriculum requirements within limited timeframes. These factors detract from teachers' core instructional functions and contribute to elevated stress levels, burnout, and attrition. The analysis highlights "time poverty" as a significant barrier, limiting teachers' ability to engage in effective pedagogy and professional development. Additionally, the study reveals that excessive workloads undermine teachers' physical and mental health, leading to reduced motivation and job dissatisfaction. To address these challenges, proposed solutions include reducing class sizes, streamlining curricular requirements, and providing additional support staff. The review underscores the necessity of educational policy reforms that prioritize teacher well-being, support effective teaching practices, and foster sustainable work environments. By alleviating workload pressures, these reforms can enhance teacher retention, professional satisfaction, and ultimately, improve educational outcomes for students. This study contributes to ongoing discussions on optimizing teacher workload to ensure high-quality education systems.

Oxidative Stress Biomarkers and Metabolic Parameters in Healthy Holstein Dairy Cows and Cows With Left Displacement Abomasum During the Transitional Period.

During the transitional period, dairy cows experience oxidative stress and are more susceptible to diseases, including left displacement of the abomasum (LDA). This study aimed to compare oxidative stress biomarker levels in cows with LDA to those in healthy conditions and investigate the associations between predictive metabolites linked to LDA and oxidative stress biomarkers. In this case-control study, 400 healthy multiparous Holstein cows were matched for lactation number, milk production and calving date. Blood samples were collected at four time points: 21 and 7 days before, as well as 7 and 21 days after parturition from all animals. During the observation period, seven cows diagnosed with LDA in the main population, and seven healthy cows were randomly selected as controls for the comparison of oxidative stress, liver enzymes and metabolic parameters. Analysis of blood parameters utilized repeated measures ANOVA, and the degree of relationship between oxidative stress biomarkers and other measured parameters was assessed using Pearson correlations. The LDA group exhibited significantly higher levels of urea, blood urea nitrogen (BUN), gamma-glutamyl transferase, glucose, cholesterol, triglyceride (TAG), β-hydroxybutyric acid (BHBA), aspartate aminotransferase (AST), sorbitol dehydrogenase, serum amyloid A (SAA), chloride, sodium, potassium, total antioxidant capacity (TAC) and malondialdehyde (MDA) compared to the control cows (p<0.05). Positive correlations were observed among BUN, glucose, TB, AST, SAA, BHBA, TAG and MDA. Conversely, these parameters displayed negative correlations with TAC. Negative correlations were found among chloride, sodium, potassium, calcium, phosphorus and MDA, whereas positive correlations were observed with TAC. These findings highlight the elevated level of oxidative stress and compromised antioxidant defence in cows with LDA and the intricate interplay among oxidative stress, metabolic parameters and liver enzymes.

Influence of stress on corrosion behavior and evolution model of Q235 steel in marine environments

The corrosion failure mechanism of Q235 steel under different stresses in simulated marine environment was investigated. The corrosion products of Q235 steel under different stresses are characterized. Additionally, electrochemical experiments and finite element simulations were conducted to examine the corrosion behavior of Q235 steel under various stress conditions. Stress promotes the corrosion failure of Q235 steel and accelerates the generation and transformation of corrosion products. Different stress levels lead to distinct stress corrosion mechanisms, with lower stress levels increasing sensitivity to corrosion. Elevated levels of stress result in stress concentration in dislocation defects, leading to more severe localized corrosion. A model for the evolution of stress corrosion failure has been established, revealing that the corrosion behavior at different stress levels is not strictly independent and can transition from low to high stress conditions under certain circumstances. Furthermore, it was observed that even at low stresses, there can be occurrences of stress concentrations leading to localized corrosion.

Lactoferrin alleviates oxidative stress and endoplasmic reticulum stress induced by autoimmune thyroiditis by modulating the mTOR pathway in the thyroid.

Autoimmune thyroiditis (AITD) is a prevalent autoimmune disorder characterized by the immune system's attack on thyroid tissue, potentially leading to thyroid dysfunction, with a current lack of effective treatment modalities. Lactoferrin, a crucial functional dietary component obtainable from food sources, primarily exists in mammalian milk. We aim to investigate whether dietary supplementation with lactoferrin can protect the thyroid in Experimental Autoimmune Thyroiditis (EAT) rats. Our study reveals significantly elevated levels of oxidative stress (OS) and endoplasmic reticulum stress (ERS) in the AITD. Lactoferrin markedly reduces OS and infiltration of inflammatory cells in the thyroid tissue of EAT rats. Furthermore, lactoferrin inhibits ERS levels in the thyroid of EAT rats and alleviates cellular apoptosis. In vivo and in vitro experiments elucidate that its protective effect is primarily achieved through the inhibition of mTOR signaling pathway activation. In summary, lactoferrin, a nutrient readily obtainable from food sources, appears to be effective in mitigating thyroid damage in AITD.

The brain under pressure: Exploring neurophysiological responses to cognitive stress

Stress is an increasingly dominating part of our daily lives and higher performance requirements at work or to ourselves influence the physiological reaction of our body. Elevated stress levels can be reliably identified through electroencephalogram (EEG) and heart rate (HR) measurements. In this study, we examined how an arithmetic stress-inducing task impacted EEG and HR, establishing meaningful correlations between behavioral data and physiological recordings. Thirty-one healthy participants (15 females, 16 males, aged 20 to 37) willingly participated. Under time pressure, participants completed arithmetic calculations and filled out stress questionnaires before and after the task. Linear mixed effects (LME) allowed us to generate topographical association maps showing significant relations between EEG features (delta, theta, alpha, beta, and gamma power) and factors such as task difficulty, error rate, response time, stress scores, and HR. With task difficulty, we observed left centroparietal and parieto-occipital theta power decreases, and alpha power increases. Furthermore, frontal alpha, delta and theta activity increased with error rate and relative response time, while parieto-temporo-occipital alpha power decreased. Practice effects on EEG power included increases in temporal, parietal, and parieto-occipital theta and alpha activity. HR was positively associated with frontal delta, theta and alpha power whereas frontal gamma power decreases. Significant alpha laterality scores were observed for all factors except task difficulty and relative response time, showing overall increases in left parietal regions. Significant frontal alpha asymmetries emerged with increases in error rate, sex, run number, and HR and occipital alpha asymmetries were also found with run number and HR. Additionally we explored practice effects and noted sex-related differences in EEG features, HR, and questionnaire scores. Overall, our study enhances the understanding of EEG/ECG-based mental stress detection, crucial for early interventions, personalized treatment and objective stress assessment towards the development of a neuroadaptive system.

Occupational health challenges among faculty in medical colleges in India: A comprehensive review

This systematic review explores the occupational health issues encountered by faculty members in medical colleges throughout India, focusing on both physical and psychological challenges. Faculty in these settings face distinct stressors stemming from the rigorous demands of academic and clinical responsibilities. The review identifies several primary challenges, including work-related musculoskeletal disorders, exposure to infectious diseases, mental health issues, elevated stress levels, burnout, and the weight of administrative burdens. These findings underscore a critical need for the development and implementation of targeted occupational health policies and supportive systems tailored specifically for medical educators. This review highlights the urgent requirement for further research aimed at devising effective intervention strategies that address the unique occupational health needs of faculty in academic medical institutions. Such research will be instrumental in fostering healthier work environments and enhancing the overall well-being of medical faculty, thereby ultimately improving educational outcomes in medical education.

Peripheral molecular and brain structural profile implicated stress activation and hyperoxidation in methamphetamine use disorder.

Methamphetamine use disorders (MUDs) cause widespread disruptions in metabolomic and immunologic processes, highlighting the need for new therapeutic approaches. The purpose of this study was to find molecular and neuroimaging biomarkers for methamphetamine addiction. In this study, we recruited 231 patients with MUD at varying stages of withdrawal and 40 healthy controls to quantify the blood levels of 52 molecules using enzyme-linked immunosorbent assay. The overall molecular disruption caused by methamphetamine was inversely related to withdrawal time (P = 0.0008), with partial recovery observed after 1 year of follow-up (P = 2.20 × 10-5). Molecules related to stress, immune activation, oxidative products, and cardiac injury were significantly elevated in all MUD groups, while antioxidation enzymes were downregulated. Additionally, the blood level of brain-derived neurotrophic factor was significantly correlated with gray matter volumes in nine brain regions (fusiform gyrus, orbitofrontal cortex, temporal pole, caudate, cerebellum crus, and vermis, adjusted P < 0.05) among patients with MUD. These findings suggest that patients with MUD exhibit elevated levels of immune response, stress, and oxidative stress, which are associated with brain structural abnormalities.

Tanshinone IIA Alleviates Pulmonary Fibrosis by Inhibiting Pyroptosis of Alveolar Epithelial Cells Through the MAPK Signaling Pathway.

The current dearth of safe and efficacious pharmaceutical interventions for pulmonary fibrosis (PF) has prompted investigations into alternative treatments. This study aim to investigate the underlying mechanisms of Tanshinone IIA in the treatment of PF. PF was induced in a mouse model by intratracheal infusion of bleomycin (BLM), followed by gavage administration of varying concentrations of Tanshinone IIA. Lung tissue was obtained for pathological slides, proteomic and transcriptomic analyses. The target was predicted and analyzed using network pharmacology. Initially, an invitro model in A549 cells was established by adding BLM, followed by treatment with varying concentrations of Tanshinone IIA. Subsequently, NAC and the ERK inhibitor, U0126, were individually introduced. Treatment with Tanshinone IIA invivo decreased lung tissue lesions. Proteomic, transcriptomic, and network pharmacology analyses suggested that Tanshinone IIA may offer therapeutic benefits for PF by mitigating oxidative stress damage via the MAPK signaling pathway. Invitro studies demonstrated that BLM treatment in A549 cells induced exposure of the N-terminal end of the pyroptosis core protein GSDMD, and elevated oxidative stress levels in A549 cells, concomitant with the upregulation of P-ERK protein expression. Subsequent administration of Tanshinone IIA, NAC, and U0126 reduced the number of A549 cells undergoing pyroptosis, decreased oxidative stress levels, and decreased P-ERK protein expression. These findings suggested that Tanshinone IIA potentially delays the progression of PF. The mechanism of action involves the inhibition of oxidative stress and reduced epithelial cell pyroptosis via the MAPK-related pathway. The findings may provide a new reference for treatment of PF.

Activation of lysosomal Ca2+ channels mitigates mitochondrial damage and oxidative stress.

Elevated levels of plasma-free fatty acids and oxidative stress have been identified as putative primary pathogenic factors in endothelial dysfunction etiology, though their roles are unclear. In human endothelial cells, we found that saturated fatty acids (SFAs)-including the plasma-predominant palmitic acid (PA)-cause mitochondrial fragmentation and elevation of intracellular reactive oxygen species (ROS) levels. TRPML1 is a lysosomal ROS-sensitive Ca2+ channel that regulates lysosomal trafficking and biogenesis. Small-molecule agonists of TRPML1 prevented PA-induced mitochondrial damage and ROS elevation through activation of transcriptional factor EB (TFEB), which boosts lysosome biogenesis and mitophagy. Whereas genetically silencing TRPML1 abolished the protective effects of TRPML1 agonism, TRPML1 overexpression conferred a full resistance to PA-induced oxidative damage. Pharmacologically activating the TRPML1-TFEB pathway was sufficient to restore mitochondrial and redox homeostasis in SFA-damaged endothelial cells. The present results suggest that lysosome activation represents a viable strategy for alleviating oxidative damage, a common pathogenic mechanism of metabolic and age-related diseases.

Harnessing hydrogen sulfide in injectable hydrogels that guide the immune response and osteoclastogenesis balance for osteoporosis treatment

Elevated levels of oxidative stress, inflammation, and a dysregulated osteoclastogenesis balance frequently characterize the microenvironment of osteoporosis, which impedes the processes of healing and repair. Existing treatment approaches are limited in scope and rely primarily on factors and drugs. An injectable hydrogel designed for the ROS-responsive release of H2S gas is presented in this study. The first network of the hydrogel comprises sodium alginate (SA-SATO) chelated with S-aroylthiooxime (SATO) and an H2S-generating group, while the second network is composed of photocrosslinkable PEGDA. Through the integration of Cys-releasing microspheres that are reactive with ROS, a composite hydrogel was developed that exhibited advantageous mechanical characteristics and biosafety. The composite hydrogel effectively promoted osteogenic differentiation of mesenchymal stem cells, modulated macrophage polarization, decreased inflammatory responses, and halted cell apoptosis, as evidenced by in vitro experiments. Additionally, it released H2S gas and mitigated excess ROS in cells. The efficacy of the composite hydrogel in promoting bone defect repair and regeneration in an osteoporotic model was further validated by in vivo findings. In summary, the composite hydrogel exhibits potential as a viable approach to address osteoporotic bone defects by harmonizing osteogenesis and osteoclast activity, modulating the microenvironment of bone injuries, and reducing inflammation. Consequently, it presents a viable strategy for the efficient repair of bone defects.

Bach2 repression of CD36 regulates lipid-metabolism-linked effector functions in follicular B cells

The transcription repressor Bach2 plays a crucial role in shaping humoral immunity, but its cell-autonomous function remains elusive. Here, we reveal the mechanism by which Bach2 regulates effector cell maturation in peripheral B cells. In response to Toll-like receptor (TLR) agonists, Bach2 deficiency promotes the differentiation of follicular, but not marginal zone, B cells into effector cells, producing interleukin (IL)-6 and antibodies. This phenomenon is associated with changes in lipid metabolism, such as increases in CD36 expression, lipid influx, and fatty acid oxidation. Consistent with this, Bach2-deficient B cells exhibit elevated levels of mitochondrial oxidative stress, lipid peroxidation, and p38 activation. Mechanistically, Bach2 acts as a repressor of Cd36, and inhibition of CD36 or fatty acid oxidation reduces the differentiation of naive B cells into IL-6- and antibody-secreting cells. These results indicate Bach2 as a key metabolic checkpoint regulator crucial for maintaining a functionally quiescent state of follicular B cells.

ANGPTL4-mediated microglial lipid droplet accumulation: Bridging Alzheimer's disease and obesity

Increasing evidence suggests that metabolic disorders such as obesity are implicated in the development of Alzheimer's disease (AD). The pathological buildup of lipids in microglia is regarded as a key indicator in brain aging and the progression of AD, yet the mechanisms behind this process remain uncertain. The adipokine ANGPTL4 is strongly associated with obesity and is thought to play a role in the advancement of neurodegenerative diseases. This study utilized RNA sequencing to identify differential expression in lipid-accumulating BV2 microglia and investigated the potential mechanism through ANGPTL4 overexpression in BV2. Subsequently, animal models and clinical data were employed to further explore alterations in circulating ANGPTL4 levels in AD. RNA sequencing results indicated a correlation between ANGPTL4 and microglial lipid accumulation. The overexpression of ANGPTL4 in microglia resulted in increased secretion of inflammatory factors, elevated oxidative stress levels, and diminished antiviral capacity. Furthermore, when simulating the coexistence of AD and obesity through combined treatment with Amyloid-Beta 1–42 peptide (Aβ) and Free Fatty Acids (FFA) in vitro, we observed a notable upregulation of ANGPTL4 expression, highlighting its potential role in the interplay between AD and obesity. In vivo experiments, we also observed a significant increase in ANGPTL4 expression in the hippocampus and plasma of APP/PS1 mice compared to wild-type controls. This was accompanied by heightened microglial activation and reduced expression of longevity-related genes in the hippocampus. Clinical data from the UK Biobank indicated that plasma ANGPTL4 levels are elevated in patients with AD when compared to healthy controls. Moreover, significantly higher ANGPTL4 levels were observed in obese AD patients relative to their non-obese counterparts. Our findings suggest that ANGPTL4-mediated microglial aging may serve as a crucial link between AD and obesity, proposing ANGPTL4 as a potential biomarker for AD.

Effects of a digital self-efficacy training in stressed university students: A randomized controlled trial.

Self-efficacy is associated with positive mental health outcomes. We developed and tested a digital self-efficacy training for daily recall of autobiographical self-efficacy memories (e.g., memories of successfully overcoming a personal challenge). In this randomized controlled trial, we investigated the effects of the week-long digital self-efficacy training on key mental health outcomes, including anxiety, stress, and hopelessness, and on self-efficacy in 93 university students (mean age 23.3 years, SD: 3.49) with elevated self-reported stress levels. Participants completed either the self-efficacy training combined with ecological momentary assessment (EMA) (training group) or EMA only (control group). We found significantly reduced hopelessness and trait anxiety in the training group compared to the control group at post-assessment (one day post intervention). Effects on ratings of self-efficacy at post-assessment were also significant when controlling for baseline self-efficacy. This stand-alone digital self-efficacy training was significantly associated with a number of positive effects on outcomes compared to a control condition, including reduced hopelessness, trait anxiety, and increased self-efficacy. Future work is needed to replicate and investigate the long-term effects of the training and explore its implementation in clinical populations. ClinicalTrials.gov Identifier: NCT05617248.

The Effect of Sleep Quality on Stress Levels in Night Shift and Non-night Shift Workers: A Cross-Sectional Study

The sleep–wake cycle, which is regulated by the endogenous circadian rhythm, is disrupted by night-shift work. Altered sleep patterns owing to shift work have been associated with irritability, depressed mood, anxiety, and nervousness. The objective of the study was to evaluate the effect of sleep quality on stress in night shift workers and non-night shift workers. A cross – sectional study was conducted in 30night shift and 30 non-night shift workers of Railway Mail Service and Postal Department, Thrissur, Kerala. Sleep quality was assessed using Pittsburg Sleep Quality Index and stress was assessed using Perceived Stress Scale. The findings revealed that a majority of night shift workers reported poor sleep quality, with a significant correlation observed between sleep quality and shift work. Furthermore, stress levels were markedly higher among night workers with poor sleep quality. Regression analysis indicated a positive association between impaired sleep quality and elevated stress levels.

Evaluating the impact of the combined acute toxicity of iron (Fe) and microplastics on Namalycastis jaya

The rising concern over heavy metals (HMs) and microplastics (MPs) pollution in marine ecosystems, primarily driven by anthropogenic activities, poses significant threats to ecological health. Understanding the combined exposure of HMs and MPs aids in toxicity assessment. In this study, we examined the combined effects of polystyrene microplastics (MPs) and iron (Fe) on oxidative stress, bioaccumulation, histopathology, and genotoxicity in Namalycastis jaya. Oxidative stress was assessed by analyzing the levels of Superoxide dismutase (SOD), Catalase (CAT), Peroxidase (POD), Malondialdehyde (MDA), and Bicinchoninic acid (BCA), while genotoxicity was evaluated using the comet assay. Bioaccumulation analysis, conducted via Inductively coupled plasma-optical emission spectrometry (ICP-OES), indicated that the highest values (4.790 µg/ml) were observed in combined exposure, emphasizing the significant increase in iron (Fe) accumulation in polychaetes facilitated by MPs. Biochemical analysis revealed that oxidative damage in polychaetes became evident within 48 h of exposure to individual contaminants. However, in the case of combined exposures, elevated stress levels were observed within just 24 h. The genotoxic assay further demonstrated a higher degree of DNA damage in the combined exposure compared to individual exposures. Similarly, histopathology revealed mild alterations in the gut epithelium in combined exposures. It is evident that MPs intensify both oxidative and DNA damage induced by Fe in polychaetes. The insights gained from this study provide valuable information for the risk assessment of Fe and MPs in environmental safety, contributing to our understanding of the complex interactions between these pollutants in marine ecosystems.

Astragaloside IV reduces mutant Ataxin-3 levels and supports mitochondrial function in Spinocerebellar Ataxia Type 3

This study investigated the therapeutic effects of astragaloside IV (AST) on spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), a neurodegenerative disorder. Human neuroblastoma SK-N-SH cells expressing mutant ataxin-3 protein with 78 CAG repeats (MJD78) were employed as an in vitro model. Protein expression analysis demonstrated that AST treatment reduced mutant ataxin-3 protein expression and aggregation by enhancing the autophagic process in MJD78 cells. Elevated oxidative stress levels in MJD78 cells were significantly reduced following AST treatment, which also enhanced antioxidant capacity, as evidenced by flow cytometry and antioxidant enzyme activity assays. Furthermore, AST treatment ameliorated mitochondrial dysfunction in MJD78 cells, including improvements in mitochondrial membrane potential, respiration, and mitochondrial dynamics. In conclusion, AST administration increased antioxidant capacity, reduced both cellular and mitochondrial oxidative stress, and improved mitochondrial quality control processes through fusion, fission, and autophagy. These mechanisms collectively reduced intracellular mutant ataxin-3 protein aggregation, thereby achieving therapeutic efficacy in the SCA3 model.

Antioxidant hydrogels for the treatment of osteoarthritis: mechanisms and recent advances.

Articular cartilage has limited self-healing ability, resulting in injuries often evolving into osteoarthritis (OA), which poses a significant challenge in the medical field. Although some treatments exist to reduce pain and damage, there is a lack of effective means to promote cartilage regeneration. Reactive Oxygen Species (ROS) have been found to increase significantly in the OA micro-environment. They play a key role in biological systems by participating in cell signaling and maintaining cellular homeostasis. Abnormal ROS expression, caused by internal and external stimuli and tissue damage, leads to elevated levels of oxidative stress, inflammatory responses, cell damage, and impaired tissue repair. To prevent excessive ROS accumulation at injury sites, biological materials can be engineered to respond to the damaged microenvironment, release active components in an orderly manner, regulate ROS levels, reduce oxidative stress, and promote tissue regeneration. Hydrogels have garnered significant attention due to their excellent biocompatibility, tunable physicochemical properties, and drug delivery capabilities. Numerous antioxidant hydrogels have been developed and proven effective in alleviating oxidative stress. This paper discusses a comprehensive treatment strategy that combines antioxidant hydrogels with existing treatments for OA and explores the potential applications of antioxidant hydrogels in cartilage tissue engineering.

Combined HDAC8 and checkpoint kinase inhibition induces tumor-selective synthetic lethality in preclinical models.

The elevated level of replication stress is an intrinsic characteristic of cancer cells. Targeting the mechanisms that maintain genome stability to further increase replication stress and thus induce severe genome instability has become a promising approach for cancer treatment. Here, we identify histone deacetylase 8 (HDAC8) as a drug target whose inactivation synergizes with the inhibition of checkpoint kinases to elicit substantial replication stress and compromise genome integrity selectively in cancer cells. We showed that simultaneous inhibition of HDAC8 and checkpoint kinases led to extensive replication fork collapse, irreversible cell-cycle arrest, and synergistic vulnerability in various cancer cells. The efficacy of the combination treatment was further validated in patient tumor-derived organoid (PDO) and xenograft mouse (PDX) models, providing important insights into patient-specific drug responses. Our data revealed that HDAC8 activity was essential for reducing the acetylation level of structural maintenance of chromosomes protein 3 (SMC3) ahead of replication forks and preventing R loop formation. HDAC8 inactivation resulted in slowed fork progression and checkpoint kinase activation. Our findings indicate that HDAC8 guards the integrity of the replicating genome, and the cancer-specific synthetic lethality between HDAC8 and checkpoint kinases provides a promising replication stress-targeting strategy for treating a broad range of cancers.

Beta-Amyloid and Its Asp7 Isoform: Morphological and Aggregation Properties and Effects of Intracerebroventricular Administration.

One of the hallmarks of Alzheimer's disease (AD) is the accumulation of aggregated beta-amyloid (Aβ) protein in the form of senile plaques within brain tissue. Senile plaques contain various post-translational modifications of Aβ, including prevalent isomerization of Asp7 residue. The Asp7 isomer has been shown to exhibit increased neurotoxicity and induce amyloidogenesis in brain tissue of transgenic mice. The toxicity of Aβ peptides may be partly mediated by their structure and morphology. In this respect, in this study we analyzed the structural and aggregation characteristics of the Asp7 isoform of Aβ42 and compared them to those of synthetic Aβ42. We also investigated the effects of intracerebroventricular (i.c.v.) administration of these peptides, a method often used to induce AD-like symptoms in rodent models. Atomic force microscopy (AFM) was conducted to compare the morphological and aggregation properties of Aβ42 and Asp7 iso-Aβ42. The effects of i.c.v. stereotaxic administration of the proteins were assessed via behavioral analysis and reactive oxygen species (ROS) estimation in vivo using a scanning ion-conductance microscope with a confocal module. AFM measurements revealed structural differences between the two peptides, most notably in their soluble toxic oligomeric forms. The i.c.v. administration of Asp7 iso-Aβ42 induced spatial memory deficits in rats and elevated oxidative stress levels in vivo, suggesting a potential of ROS in the pathogenic mechanism of the peptide. The findings support the further investigation of Asp7 iso-Aβ42 in translational research on AD and suggest its involvement in neurodegenerative processes.