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Neural Regeneration Research Jun 2024Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits...
Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly, metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore, the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood-brain barrier function. However, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could provide valuable insights into potential therapeutic strategies for Alzheimer's disease and related conditions.
PubMed: 38934388
DOI: 10.4103/NRR.NRR-D-23-01865 -
Neural Regeneration Research Jun 2024Mature oligodendrocytes form myelin sheaths that are crucial for the Insulation of axons and efficient signal transmission in the central nervous system. Recent evidence...
Mature oligodendrocytes form myelin sheaths that are crucial for the Insulation of axons and efficient signal transmission in the central nervous system. Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons. Despite the recognition of potential heterogeneity in mature oligodendrocyte function, a comprehensive summary of mature oligodendrocyte diversity is lacking. We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes. Indeed, recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences. Furthermore, modern molecular investigations, employing techniques such as single cell/nucleus RNA sequencing, consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region. Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis, Alzheimer's disease, and psychiatric disorders. Nevertheless, caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations. Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity. Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species, sex, central nervous system region, age, and disease, hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.
PubMed: 38934385
DOI: 10.4103/NRR.NRR-D-24-00055 -
Frontiers in Aging Neuroscience 2024Dementia is a progressive neurodegenerative condition, while metabolic syndrome (MetS) is characterized by a combination of metabolic abnormalities such as hypertension,...
BACKGROUND
Dementia is a progressive neurodegenerative condition, while metabolic syndrome (MetS) is characterized by a combination of metabolic abnormalities such as hypertension, high blood sugar, and obesity. There exists a connection and overlap between the two conditions in certain aspects, and both are influenced to varying degrees by the process of aging. This study presents an overview of the current research landscape regarding dementia and MetS through bibliometric analysis.
METHODS
A systematic search was conducted to retrieve relevant literature on dementia and MetS published between 1 January 2000, and 30 November 2023, from the Web of Science Core Collection database. Various bibliometric tools, including VOSviewer, CiteSpace, and the R software package "bibliometrix," were utilized for analysis.
RESULTS
A total of 717 articles were identified, showing an upward trend in annual publications. Leading contributors included the United States, Italy, and China, with institutions such as the University of California System at the forefront. The emerged as the top publisher, while research published in garnered significant citations. Noteworthy authors encompassed Panza, Francesco; Frisardi, Vincenza; and Feldman, Eva L, with Kristine Yaffe being the most cited author (280 citations). Recent studies have focused on themes like "gut microbiota," "neuroinflammation," "fatty acids," and "microglia."
CONCLUSION
This bibliometric analysis summarizes the foundational knowledge structure in the realm of dementia and MetS from 2000 to 2023. By highlighting current research frontiers and trending topics, this analysis serves as a valuable reference for researchers in the field.
PubMed: 38934020
DOI: 10.3389/fnagi.2024.1400589 -
Frontiers in Aging Neuroscience 2024Changes in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday...
Amyloid and tau burden relate to longitudinal changes in the performance of complex everyday activities among cognitively unimpaired older adults: results from the performance-based Harvard Automated Phone Task.
BACKGROUND
Changes in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday functioning might help uncover these early changes. We aimed to investigate how changes over time in everyday functioning relate to tau and amyloid in cognitively unimpaired older adults.
METHODS
Seventy-six cognitively unimpaired participants (72 ± 6 years old, 61% female) completed multiple Harvard Automated Phone Task (APT) assessments over 2.0 ± 0.9 years. The Harvard APT consists of three tasks, performed through an automated phone system, in which participants refill a prescription (APT-Script), select a new primary care physician (APT-PCP), and transfer money to pay a bill (APT-Bank). Participants underwent Pittsburgh compound-B and flortaucipir positron emission tomography scans at baseline. We computed distribution volume ratios for a cortical amyloid aggregate and standardized uptake volume ratios for medial temporal and neocortical tau regions. In separate linear mixed models, baseline amyloid by time and tau by time interactions were used to predict longitudinal changes in performance on the Harvard APT tasks. Three-way amyloid by tau by time interactions were also investigated. Lastly, we examined associations between tau and change in Harvard APT scores in exploratory voxel-wise whole-brain analyses. All models were adjusted for age, sex, and education.
RESULTS
Amyloid [unstandardized partial regression coefficient estimate (β) = -0.007, 95% confidence interval (95% CI) = (-0.013, -0.001)], and medial temporal tau [β = -0.013, 95% CI = (-0.022, -0.004)] were associated with change over time in years on APT-PCP only, i.e., higher baseline amyloid and higher baseline tau were associated with steeper rate of decline of APT-PCP. Voxel-wise analyses showed widespread associations between tau and change in APT-PCP scores over time.
CONCLUSION
Even among cognitively unimpaired older adults, changes over time in the performance of cognitively complex everyday activities relate to cortical amyloid and widespread cerebral tau burden at baseline. These findings support the link between Alzheimer's disease pathology and function and highlight the importance of measuring everyday functioning in preclinical disease stages.
PubMed: 38934017
DOI: 10.3389/fnagi.2024.1420290 -
Health Affairs Scholar Jun 2024Enrollment in Medicare Advantage (MA) has been rapidly growing. We examined whether MA enrollment affects the outcomes of post-acute nursing home care among patients...
Enrollment in Medicare Advantage (MA) has been rapidly growing. We examined whether MA enrollment affects the outcomes of post-acute nursing home care among patients with Alzheimer's disease and related dementias (ADRD). We exploited year-to-year changes in MA penetration rates within counties from 2012 through 2019. After adjusting for patient-level characteristics and county fixed effects, we found that MA enrollment was not associated with days spent at home, nursing home days, likelihood of becoming a long-stay resident, hospital days, hospital readmission, or 1-year mortality. There was a modest increase in successful discharge to the community by 0.73 percentage points (relative increase of 2.4%) associated with a 10-percentage-point increase in MA enrollment. The results are consistent among racial/ethnic subgroups and dual-eligible patients. These findings suggest an imperative need to monitor and improve quality of managed care among enrollees with ADRD.
PubMed: 38934015
DOI: 10.1093/haschl/qxae084 -
Food Chemistry: X Oct 2024Most phenolic compounds in beans exist in complex, insoluble binding forms that bind to cell wall components ether, ester, or glucoside bonds. In the process of...
Most phenolic compounds in beans exist in complex, insoluble binding forms that bind to cell wall components ether, ester, or glucoside bonds. In the process of solid-state fermentation, can produce many hydrolase enzymes, such as α-amylase, pectinase, cellulase and β-glucosidase, which can effectively hydrolyze ether, ester or glucoside bond, release bound polyphenols, and increase polyphenol content in soybeans. When the fermentation conditions of soybean were fermentation time 12 days, inoculation amount 15% and initial pH 2, the content of free polyphenols in fermented soybean was 2.79 mg GAE/g d.w, which was 4.98 times that of unfermented soybean. The contents of bound polyphenols and total phenols in fermented soybean were 0.62 mg GAE/g d.w and 3.41 mg GAE/g d.w, respectively, which were 2.38 times and 4.16 times of those in unfermented soybean. At the same time, the inhibitory effect of free polyphenols in fermented soybean on acetylcholinesterase reached 91.51%. Thus, our results demonstrated that solid state fermentation and can be used as an effective way to increase soybean polyphenol content and combat Alzheimer's disease.
PubMed: 38933989
DOI: 10.1016/j.fochx.2024.101526 -
Frontiers in Neuroscience 2024Parkinson's disease (PD) is a common neurodegenerative disease with a rapid increase in incidence in recent years. Existing treatments cannot slow or stop the...
BACKGROUND
Parkinson's disease (PD) is a common neurodegenerative disease with a rapid increase in incidence in recent years. Existing treatments cannot slow or stop the progression of PD. It was proposed that neuroinflammation leads to neuronal death, making targeting neuroinflammation a promising therapeutic strategy. Our previous studies have demonstrated that rhein protects neurons by inhibiting neuroinflammation, and it has been found to exhibit neuroprotective effects in Alzheimer's disease and epilepsy, but its neuroprotective mechanisms and effects on PD are still unclear.
METHODS
PD animal model was induced by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP). ELISA, RT-qPCR, western blot and Immunofluorescence were used to detect the levels of inflammatory cytokines and M1 polarization markers. The protein expression levels of signaling pathways were measured by western blot. Hematoxylin-eosin (HE) staining showed that rhein did not damage the liver and kidney. Two behavioral tests, pole test and rotarod test, were used to evaluate the improvement effect of rhein on movement disorders. The number of neurons in the substantia nigra was evaluated by Nissl staining. Immunohistochemistry and western blot were used to detect tyrosine hydroxylase (TH) and α-synuclein.
RESULTS
Rhein inhibited the activation of MAPK/IκB signaling pathway and reduced the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and M1 polarization markers of microglia . In a mouse model of PD, rhein ameliorated movement disorders, reduced dopaminergic neuron damage and α-synuclein deposition.
CONCLUSION
Rhein inhibits neuroinflammation through MAPK/IκB signaling pathway, thereby reducing neurodegeneration, α-synuclein deposition, and improving movement disorders in Parkinson's disease.
PubMed: 38933815
DOI: 10.3389/fnins.2024.1396345 -
Frontiers in Immunology 2024Air pollution is an urgent concern linked to numerous health problems in low- and middle-income countries, where 92% of air pollution-related deaths occur. Particulate... (Review)
Review
Air pollution is an urgent concern linked to numerous health problems in low- and middle-income countries, where 92% of air pollution-related deaths occur. Particulate matter 2.5 (PM) is the most harmful component of air pollutants, increasing inflammation and changing gut microbiota, favoring obesity, type 2 diabetes, and Alzheimer's Disease (AD). PM contains lipopolysaccharides (LPS), which can activate the Toll-like receptor 4 (TLR4) signaling pathway. This pathway can lead to the release of pro-inflammatory markers, including interleukins, and suppressor of cytokine signaling-3 (SOCS3), which inhibits leptin action, a hormone that keeps the energy homeostasis. Leptin plays a role in preventing amyloid plaque deposition and hyperphosphorylation of tau-protein (p-tau), mechanisms involved in the neurodegeneration in AD. Approximately 50 million people worldwide are affected by dementia, with a significant proportion living in low-and middle-income countries. This number is expected to triple by 2050. This mini-review focuses on the potential impact of PM exposure on the TLR4 signaling pathway, its contribution to leptin resistance, and dysbiosis that exacerbates the link between obesity and AD.
Topics: Humans; Alzheimer Disease; Obesity; Leptin; Air Pollution; Particulate Matter; Toll-Like Receptor 4; Inflammation; Animals; Signal Transduction; Air Pollutants
PubMed: 38933275
DOI: 10.3389/fimmu.2024.1401800 -
Fundamental Research May 2024
PubMed: 38933187
DOI: 10.1016/j.fmre.2024.03.009 -
Dementia & Neuropsychologia 2024The world's population is experiencing an aging process, which is resulting in an increase in diseases such as Alzheimer's disease. Consequently, more and more people...
UNLABELLED
The world's population is experiencing an aging process, which is resulting in an increase in diseases such as Alzheimer's disease. Consequently, more and more people need care, which can lead to overload and harm to their family's quality of life.
OBJECTIVE
Identify the psychosocial factors affected by the burden on family caregivers of people with Alzheimer's disease.
METHODS
Forty-nine family caregivers of people with Alzheimer's disease, from a city in Minas Gerais, Brazil, participated in the study. They filled out a form of sociodemographic variables, and answered the Burden Interview Scale (BI-Zarit), Quality of Life in Alzheimer's Disease Caregiver version (CQoL-AD), the Depression, Anxiety and Stress Scale (DASS-21), the Mindfulness and Awareness Scale (MAAS) and the Clinical Dementia Rating Scale (CDR).
RESULTS
All participants were female with an average age of 54.26 (±8.99). Daughters comprised 77.55% of the sample, and 34.69% were sole caregivers. The Bi-Zarit scale positively and significantly correlated with DASS-21 Depression (r=0.440; p=0.002), DASS-21 Anxiety (r=0.415; p=0.003), DAAS-21 Stress (r=0.583; p<0.001). On the other hand, it showed a negative correlation with MAAS (r=-0.429; p=0.002) and CQoL-AD (r=-0.533; p<0.001).
CONCLUSION
This study demonstrates that family caregivers of people with Alzheimer's disease may be overloaded, and that the heavier the burden, the lower level of attention, the worse quality of life and the greater the possibility for the caretaker to present symptoms of depression, anxiety, and stress.
PubMed: 38933081
DOI: 10.1590/1980-5764-DN-2023-0115