Frontiers in Aging Neuroscience最新文献

Introduction: Neurosphere culture is widely used to expand neural stem and progenitor cells (NSPCs) of the nervous system. Understanding the identity of NSPCs, such as the principals involved in spatiotemporal patterning, will improve our chances of using NSPCs for neurodevelopmental and brain repair studies with the ability to direct NSPCs toward distinct fates. Some reports indicate that aging can affect the nature of NSPCs over time. Therefore, in this study, we aimed to investigate how the initial neural patterning of developing NSPCs changes over time.

Methods: In this research, evidence of changing neural patterning potential in the nervous system over time was presented. Thus, the embryonic and adult-derived NSPCs for cardinal characteristics were analyzed, and then, the expression of candidate genes related to neural patterning using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was evaluated at various stages of embryonic (E14 and E18), neonatal, and adult brains. Finally, it was assessed the effect of cell attachment and passage on the initial neural patterning of NSPCs.

Results: The analysis of gene expression revealed that although temporal patterning is maintained in vitro, it shows a decrease over time. Embryonic NSPCs exhibited the highest potential for retaining regional identity than neonatal and adult NSPCs. Additionally, it was found that culture conditions, such as cell passaging and attachment status, could affect the initial neural patterning potential, resulting in a decrease over time.

Conclusion: Our study demonstrates that patterning potential decreases over time and aging imposes restrictions on preliminary neural patterning. These results emphasize the significance of patterning in the nervous system and the close relationship between patterning and fate determination, raising questions about the application of aged NSPCs in the treatment of neurodegenerative diseases.

Introduction: The role of the chemokine CX3CL1 in the processes of aging and Alzheimer's disease (AD) pathogenesis is well-established. This study aims to evaluate the diagnostic potential of urinary CX3CL1 levels in distinguishing between AD patients, those experiencing amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) individuals.

Methods: A cohort comprising 516 CN individuals across various age groups, 102 AD patients, and 65 subjects with aMCI was assembled, alongside 93 age- and sex-matched CN controls. Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify urinary CX3CL1 levels.

Results: Urinary CX3CL1 concentrations exhibited an age-dependent increase and demonstrated a positive correlation with age. Comparatively, AD patients exhibited significantly elevated urinary CX3CL1 levels when contrasted with both the CN controls and the aMCI cohort. Conversely, aMCI patients displayed urinary CX3CL1 levels that were notably reduced in comparison to both the AD and CN groups.

Conclusion: Urinary CX3CL1 levels correlate with the aging process and may serve as a potential diagnostic biomarker for both amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD).

Introduction: Lingguizhugan decoction (LGZG) has been reported to treat Alzheimer's disease (AD) by anti-inflammatory and transporting amyloid-β (Aβ).

Methods: Using APP/PS1 transgenic mice as in vivo model and gave LGZG decoction by oral gavage. Using Aβ_25-35-induced SH-SY5Y cells as in vitro model and then added LGZG medicated serum (LMS) to observe the regulatory effect of LGZG on AD autophagy-related pathways. Morris water maze (MWM) was used to evaluate the mice's learning and memory ability. Mice's hippocampus tissue sections were stained immunohistochemically to observe hippocampal Aβ deposition. Transmission electron microscopy monitored autophagosomes and autolysosomes. Western blot analysis measured protein expression levels of beclin-1, p62 and light chain 3II (LC3 II) and mTOR signaling. Results: LGZG could greatly improve learning and memory ability of APP/PS1 mice, and enhance autophagy in vitro and in vivo. LGZG increased the levels of beclin-1 and LC3 II and decreased the levels of p62.

Conclusion: LGZG enhanced autophagy and showed therapeutic potential in AD by inhibiting mTOR/p70s6K signaling.

Background: The demand for more accurate and early diagnosis of mild cognitive impairment (MCI) patients due to Alzheimer's disease (AD) has increased after disease-modifying drugs were launched. Among these needs, there is a requirement for tools that can easily assess the ability to recall memories, which changes early in the disease.

Objectives: We established Self Assessment Memory Scale (SAMS) method before, which includes 8-picture recall test and 16-word recognition test. We adopted this method to software that can be operated on a tablet computer so that participants can perform the method independently. The purpose of this study was to validate this method.

Design: Cross sectional research.

Setting: Some of the participants were recruited from hospitals for patients diagnosed with AD or MCI. The others were recruited from three regional cohorts of healthy older adults.

Participants: The total number of participants was 304 (20 of whom had AD or MCI), and the mean age was 71.2 years. 64% of the participants were women.

Measurements: We used the logical memory subtest of the WMS-R as the standard for memory evaluation and assessed the relationship between this score and the SAMS score calculated by the software.

Results: The 2nd SAMS score were higher than the 1st SAMS score in some participants, on the other hand, the intraclass correlation coefficient was good. Since the number of false recognition in the 16-word recognition test was higher in participants with lower LM II scores, we developed a new score to reflect the ratio of false recognition, SAMS-R, and we observed it has good correlation with LM II. The mean SAMS-R score decreased gradually after the age of 65 years, indicating that age-related changes in memory recall can be detected. The ROC curve analysis was conducted to evaluate the detectability to determine whether if the WMS-R LM II score is above or below 10, showing that the AUC was greater than 0.9.

Conclusion: SAMS-R, which can be performed on a tablet literally by himself/herself independently, shows a high correlation with the WMS-R Logical Memory II score, and has the advantage of being performed in a short time without the need for a clinical psychologist or other personnel.

Background: Obesity, through mechanisms such as insulin resistance and systemic low-grade inflammation, can damage the central nervous system and impair cognitive function. Weight-adjusted waist index (WWI) is a novel measure of obesity that may offer more precise assessments of muscle and fat mass. This study aims to investigate the association between WWI and cognitive function in older Chinese men.

Methods: Data from the 2011-2018 China Longitudinal Health and Longevity Survey (CLHLS) were used in this study. WWI and cognitive function were examined in both linear and non-linear situations using Kaplan-Meier survival curves, multivariate Cox regression models, and restricted cubic spline (RCS) regression.

Results: This study included 1,392 older Chinese men aged 65 years and over for whom complete data were available. After controlling for all potential confounding variables, our analysis showed a statistically significant positive association between WWI and cognitive decline. Specifically, for every 1 cm/√kg increase in WWI, the risk of cognitive impairment increased by 17% (HR = 1.17, 95% CI: 1.02-1.35). Using 11.52 cm/√kg as the cutoff point for WWI, we found that High WWI was associated with a 44% increased risk of cognitive impairment compared with Low WWI (HR = 1.44, 95% CI: 1.07-1.96). RCS regression analysis confirmed a linear positive correlation between WWI and cognitive impairment.

Conclusion: Higher WWI is linked to worse cognitive performance in older Chinese men.

The Chilean degu (Octodon degus) is a medium sized, long-lived rodent with traits that make them a natural model for neuroscience research. Their social behaviors, diurnality, and extended developmental time course, when compared to other rodents, make them useful for social behavioral, chronobiology, and developmental research. Lab-kept degus have a long lifespan (5-8 years) and may naturally develop age-related diseases that resemble Alzheimer's disease. While there is significant interest in using the Octodon degus for neuroscience research, including aging and Alzheimer's disease studies, laboratory management and methods for degus research are currently not standardized. This lack of standardization potentially impacts study reproducibility and makes it difficult to compare results between different laboratories. Degus require species-specific housing and handling methods that reflect their ecology, life history, and group-living characteristics. Here we introduce major principles and ethological considerations of colony management and husbandry. We provide clear instructions on laboratory practices necessary for maintaining a healthy and robust colony of degus for Alzheimer's disease neuroscience research towards conducting reproducible studies. We also report detailed procedures and methodical information for degu Apoe genotyping and ethologically relevant burrowing behavioral tasks in laboratory settings.

Background: Serum Neurofilament Light chain (NfL) is a promising biomarker of neuronal damage, used to assess the extent of neuronal injury and neurodegeneration, and it is widely applied in the diagnosis of neurodegenerative disease and monitoring disease progression. This article aims to determine whether serum NfL associated with cognitive level.

Methods: Using NHANES data, we conducted an analysis of cognitive test results for 450 adults aged 60 years and older and examined their correlation with serum NfL levels. When exploring the association between cognitive test scores and serum NfL levels, regression models and restricted cubic spline (RCS) regression models were employed to adjust for potential confounding factors. The least absolute shrinkage and selection operator (LASSO) regression was applied for identifying key cognitive impairment factors, which was then included in the establishment of a risk prediction nomogram model, with the receiver operating characteristic (ROC) curve being built to evaluate its discriminatory power for cognitive impairment.

Results: It was found that there is a strong positive correlation between serum NfL levels and both low total cognitive function (total-CF) OR: 1.028 (95%CI = 1.015-1.041 p < 0.001) and low Digit Symbol Substitution Test (DSST) OR: 1.026 (95%CI = 1.003-1.050, p = 0.027). Furthermore, using the RCS model, we observed a linear trend in the relationship between NfL and low total-CF. The nomogram model based on NfL identified by LASSO regression displayed a considerable predicative value for low total-CF, with an area under the curve [AUC = 85.6% (81.6-89.3%)].

Conclusion: There is a strong correlation between serum NfL levels and cognitive function, especially DSST, which reflects attention and information processing abilities, as well as overall cognitive function, but not memory and language fluency. Thus, NfL may serve as a serum biomarker for dementia monitoring.

Objective: This study investigates the interplay between muscle strength, information processing speed, EEG-specific biomarkers, and cognitive function in elderly individuals with cognitive impairments, emphasizing the mediating roles of information processing speed and EEG-specific biomarkers.

Method: A cross-sectional study design was employed to recruit 151 elderly participants. The participants underwent grip strength and 30-s sit-to-stand tests to assess muscle strength, completed the Trail Making Test part A (TMT-A) and the Symbol Digit Modality Test (SDMT) to evaluate information processing speed, and utilized the Montreal Cognitive Assessment (MOCA) to gauge cognitive function. Additionally, EEG signals were recorded for 5 min to capture neural activity.

Results: The difference in information processing speed among elderly individuals with varying degrees of cognitive impairment was statistically significant (p < 0.001). A significant negative correlation was observed between the MoCA score and the time consumption of TMT-A (r = -0.402, p < 0.01), and a significant positive correlation was found between the MoCA score and the SDMT score (r = 0.609, p < 0.01). Grip strength was negatively correlated with the time consumption of TMT-A (r = -0.336, p < 0.01) and positively correlated with the SDMT score (r = 0.336, p < 0.01). A significant negative correlation was found between the 30-s sit-to-stand test and the time consumption of TMT-A (r = -0.273, p < 0.01), and a significant positive correlation was observed between the 30-s sit-to-stand test and the SDMT score (r = 0.372, p < 0.01). Additionally, we observed that the α1 power value indicators were significantly correlated with the MoCA score, the time consumption of TMT-A, and the SDMT score (all p < 0.01). The α1 power values at F7 + F8 and T5 + T6 were identified as sensitive EEG indicators for muscle strength and information processing speed. The EEG-specific indicators (B = 0.019, 95% CI: 0.003, 0.047) and information processing speed (B = 0.137, 95% CI: 0.096, 0.292) were found to partially mediate the relationship between grip strength and MoCA scores, with information processing speed exerting a stronger mediating effect.

Conclusion: Specific patterns were observed in the EEG of elderly individuals with cognitive impairments, which could objectively assess the risk of cognitive decline in this population. Muscle strength, information processing speed, and EEG-specific biomarkers were closely associated with cognitive function in elderly individuals. The potential pathway of interaction-muscle strength → EEG-specific biomarkers → information processing speed → cognitive function-provides valuable insights into advancing the field of cognitive research in the elderly.

Background: Iron deposition has been observed in Parkinsonism and is emerging as a diagnostic marker for movement disorders. Brain functional network disruption has also been detected in parkinsonism, and is believed to be accountable for specific symptoms in parkinsonism. However, how iron deposition influences brain network remains to be elucidated.

Methods: We recruited 16 Parkinson's disease (PD), 8 multiple system atrophy (MSA) and 7 progressive supranuclear palsy (PSP) patients. T1-weighted, susceptibility weighted images and resting-state functional MRI (rs-fMRI) were acquired. Quantitative susceptibility mapping (QSM) analysis was performed to quantify iron deposition in substantia nigra, putamen and dentate nucleus. Cerebellar network, sensorimotor network, default mode network and language networks were segregated using independent analysis. Network and iron deposition status were evaluated in relation to diagnostic groups, motor and non-motor symptoms. The relationship between quantitative iron deposition and brain network status was further interrogated. To further validate the findings, 13 healthy controls and 37 PD patients who had available T1 and rs-fMRI scans were selected from Parkinson's progression markers initiative (PPMI) database, and network analysis was performed.

Results: In local cohort, compared to PD, MSA patients showed greater iron deposition in putamen, while PSP patients had greater iron deposition in caudate nucleus and thalamus. Cerebellar and language networks showed significant difference across diagnostic groups, while default mode network and sensorimotor network did not. MSA patients had significantly impaired cerebellar network and language networks compared to PD patients. Cerebellar network was positively associated with motor symptom scores while language network was positively associated with MoCA scores in the patients. Iron deposition was negatively associated with both networks' activity in the patients. In PPMI cohort, impairment was found in both cerebellar and language networks in PD. Cerebellar and language networks correlated with motor and cognitive impairment, respectively.

Conclusion: Cerebellar network and language networks are differently influenced in MSA, PD and PSP, which can serve as potential diagnostic marker. Impairment of cerebellar network and language network are associated with motor symptoms and cognitive impairment, respectively. Moreover, dysfunction of the networks is associated with iron deposition in deep nuclei (SN, DN, Putamen).

Aging and age-related disease are among the most common and challenging issues worldwide. During the aging process, the accumulation of oxidative stress, DNA damage, telomere dysfunction, and other related changes lead to cellular dysfunction and the development of diseases such as neurodegenerative and cardiovascular conditions. Curcumin is a widely-used dietary supplement against various diseases such as cancer, diabetes, cardiovascular diseases and aging. This agent mediates its effects through several mechanisms, including the reduction of reactive oxygen species (ROS) and oxidative stress-induced damage, as well as the modulation of subcellular signaling pathways such as AMPK, AKT/mTOR, and NF-κB. These pathways are involved in cellular senescence and inflammation, and their modulation can improve cell function and help prevent disease. In cancer, Curcumin can induce apoptosis in a variety of different tumor cell lines. Curcumin also activates redox reactions within cells inducing ROS production that leads to the upregulation of apoptosis receptors on the tumor cell membrane. Curcumin can also upregulate the expression and activity of p53 that inhibits tumor cell proliferation and increases apoptosis. Furthermore, curcumin has a potent inhibitory effect on the activity of nuclear factor kappa B (NF-κB) and cyclooxygenase-2 (COX-2), which are involved in the overexpression of antiapoptosis genes such as Bcl-2. It can also attenuate the regulation of antiapoptosis phosphoinositide 3-kinases (PI3K) signaling and increase the expression of mitogen-activated protein kinases (MAPKs) to induce endogenous production of ROS. Therefore, herein, we aim to summarize how curcumin affect different epigenetic processes (such as apoptosis and oxidative stress) in order to change aging-related mechanisms. Furthermore, we discuss its roles in age-related diseases, such as Alzheimer, Parkinson, osteoporosis, and cardiovascular diseases.