La Jolla Institute for Immunology’s Post

Immune memory in brain astrocyte The study found that astrocytes can remember previous interactions with immune cells, acquire developing faster and stronger pro-inflammatory responses upon subsequent re-challenge with immune stimuli. These findings resemble classic descriptions of immune memory in immune cells, hence the investigators have termed it astrocyte immune memory, to differentiate it from described roles of astrocytes in cognitive memory. Considering the longevity of astrocytes, and their multiple contributions to CNS pathology, the authors suggest that astrocyte immune memory might be a possible mechanism behind chronic neurologic disorders. In a series of in vivo and in vitro studies, the investigators established that astrocyte immune memory is driven by an epigenetic program driven by p300 and ATP-citrate lyase (ACLY) — enzymes that help increase gene activity. The team found that astrocytes expressing p300 and ACLY were upregulated in mouse models of multiple sclerosis (MS), and that astrocyte-specific inactivation of these genes suppressed CNS inflammation and disease progression. The researchers also observed astrocyte memory in vitro in human cells and detected elevated levels of ACLY+p300+astrocytes in chronic MS human patient samples, indicating a potential role of astrocyte memory in disease pathology. #ScienceMission #sciencenewshighlights https://lnkd.in/gqqbcNwr

"Study Findings Provide New Hope for Patients With Multiple Sclerosis" New research led by Yale University sheds light on a potential breakthrough in understanding and treating multiple sclerosis (MS) and possibly other autoimmune diseases. This Yale-led study identifies a key protein, PRDM1-S, which plays a crucial role in immune dysfunction by promoting overexpression of a salt-sensitive enzyme, SGK-1. The disruption of regulatory T cells lead to a loss of immune regulation, a mechanism thought to contribute to MS. This builds on past findings showing high salt intake as a contributor to inflammation in MS and potentially opens new doors for therapeutic targeting. The findings, published in Science Translational Medicine, suggest that therapies that reduce PRDM1-S expression could restore regulatory T-cell function. Dr. Tomokazu Sumida and Dr. David Hafler, the study's leaders, are now collaborating with Yale researchers to develop computational methods to strengthen regulatory T cells across autoimmune conditions. Dr. Hafler notes that these results provide "mechanistic insight" into Treg dysfunction, setting the stage for innovative treatment options. 📄 Explore the full study here: https://lnkd.in/dqF7WCUp #MultipleSclerosis #AutoimmuneResearch #Neurology #MedicalBreakthrough #Immunology #PrecisionMedicine #HealthcareInnovation #RegulatoryTCells

🚨 𝗡𝗲𝘄 𝗣𝘂𝗯𝗹𝗶𝗰𝗮𝘁𝗶𝗼𝗻 𝗔𝗹𝗲𝗿𝘁! 🚨 Excited to share our latest study, “𝗠𝘂𝗹𝘁𝗶𝗽𝗹𝗲 𝗦𝗰𝗹𝗲𝗿𝗼𝘀𝗶𝘀 𝗣𝗮𝘁𝗶𝗲𝗻𝘁 𝗠𝗮𝗰𝗿𝗼𝗽𝗵𝗮𝗴𝗲𝘀’ 𝗜𝗺𝗽𝗮𝗶𝗿𝗲𝗱 𝗠𝗲𝘁𝗮𝗯𝗼𝗹𝗶𝘀𝗺 𝗟𝗲𝗮𝗱𝘀 𝘁𝗼 𝗮𝗻 𝗔𝗹𝘁𝗲𝗿𝗲𝗱 𝗥𝗲𝘀𝗽𝗼𝗻𝘀𝗲 𝘁𝗼 𝗔𝗰𝘁𝗶𝘃𝗮𝘁𝗶𝗼𝗻 𝗦𝘁𝗶𝗺𝘂𝗹𝗶.” Our research reveals how metabolic dysfunction in MS patient macrophages drives them toward a CD16+ proinflammatory state, impairing their role in both inflammation control and neuroregeneration. This shift, coupled with a mitochondrial energy block, reduces their myelin-clearing abilities and impacts nerve cell differentiation. These findings underscore macrophages’ potential as therapeutic targets in MS. 🧠🔬 Huge congratulations to all the authors, especially Violetta Zujovic and Jennifer Fransson, for their incredible work! Always a pleasure working with farid I.! Read more about our findings here: https://lnkd.in/e-pAzWZe #MultipleSclerosis #Immunology #Macrophages #Neuroregeneration #Research IHU ICAN Institut du Cerveau – Paris Brain Institute

Not enough Testosterone worsens mitochondrial dysfunction in Alzheimer's model mice 🟣Background: Recent studies indicate that testosterone (T) deficiency worsens cognitive impairment in Alzheimer's disease (AD) patients. Mitochondrial dysfunction is a critical hallmark of AD pathogenesis. However, the relationship between T deficiency and mitochondrial dysfunction in men with AD remains unclear. 🟣Objective: This study explores the effects of T deficiency on mitochondrial dysfunction in male AD mouse models and its potential mechanisms. 🟣Methods: A male AD animal model with T deficiency was created by castrating 3-month-old male APP/PS1 mice. Researchers analyzed hippocampal mitochondrial function using spectrophotometry and flow cytometry, and determined gene expression levels related to mitochondrial biogenesis and dynamics through qPCR and western blot analysis. SH-SY5Y cells treated with flutamide, T, and/or H2O2 were used to study the potential mechanisms of T on mitochondrial dysfunction. 🟣Results: Testosterone deficiency significantly aggravated cognitive deficits and hippocampal damage in male APP/PS1 mice. This was linked to worsened mitochondrial dysfunction, evidenced by increased oxidative damage, decreased mitochondrial membrane potential, complex IV activity, and ATP levels. T deficiency disrupted mitochondrial homeostasis, impairing mitochondrial biogenesis and dynamics at the mRNA and protein levels, leading to more defective mitochondria in the hippocampus. In vitro studies confirmed T's protective effects on mitochondrial dysfunction, biogenesis impairment, and dynamics imbalance. The use of flutamide, an androgen receptor antagonist, weakened T's beneficial effects, highlighting the critical role of the androgen receptor pathway in maintaining mitochondrial function. 🔴 Conclusion: Testosterone deficiency exacerbates hippocampal mitochondrial dysfunction in male APP/PS1 mice, accumulating more defective mitochondria. Maintaining appropriate T levels in the early stages of AD might delay AD pathology by improving mitochondrial biogenesis and dynamics. link: https://lnkd.in/gXayJMj3 #Testosterone #AlzheimersDisease #MitochondrialDysfunction #CognitiveHealth #Neurodegeneration #HealthResearch #InnovativeTherapies

UVA School of Medicine researchers discovered a gene on the Y chromosome that contributes to the greater incidence of heart failure in men. Y chromosome loss in men occurs progressively throughout life and can be detected in approximately 40% of 70-year-old men. UVA’s Kenneth Walsh, PhD, discovered in 2022 that this loss can contribute to heart muscle scarring and lead to deadly heart failure. (That finding was the first to directly link Y chromosome loss to a specific harm to men’s health; Y chromosome loss is increasingly thought to play a role in diseases ranging from Alzheimer’s to cancer.) In an important follow-up finding, Walsh and his team have discovered how Y chromosome loss triggers changes in heart immune cells that make the cells more likely to cause scarring and heart failure.

🔴NEW PAPER ALERT "Neuroinflammation in Alzheimer disease", published in Springer Nature. Agustín Ruiz Laza et al. Scientific evidence highlights the key role of immune processes in the development of Alzheimer’s, the most common neurodegenerative disease. Experimental, genetic, and epidemiological studies suggest that the activation of both innate and adaptive immune systems contributes to its progression. This article examines the cells and mechanisms involved, as well as the influence of genetic and lifestyle factors. Additionally, it highlights new therapies targeting neuroinflammation, which are now being tested in patients with promising results. Read it 👇:

💎💎💎Whatsapp!! 💎💎💎Multiple Sclerosis & Myelin Sheath #Myelin #Sheath Damage Mediated by Epigenetic #Remedy in #Multiple #Sclerosis Despite being one of the most common and well-known #neurodegenerative #diseases, multiple sclerosis ( #MS) remains difficult to treat. However, new research from scientists at Cincinnati Children’s Hospital Medical Center and elsewhere points to a #potential #therapeutic approach that appears to overcome difficulties faced by other attempts. Their work is described in a new Cell paper titled, “#Small_molecule_induced epigenetic rejuvenation promotes SREBP condensation and overcomes barriers to #CNS myelin regeneration.” According to the paper, the researchers treated mouse models of multiple sclerosis and myelin #organoids with an inhibitor molecule called epigenetic-silencing-inhibitor-1 (ESI1) that appears to improve both myelin production and poor #cognitive function associated with MS and similar #demyelinating diseases. It works at the epigenetic level to essentially restart myelin production by #oligodendrocytes present in the MS lesions... ➡ 💎 You can find more pieces of work by clicking here. https://lnkd.in/eSG67K5G https://lnkd.in/dB3s88ei #Myelin #Sheath #Epigenetic #Remedy #Multiple #Sclerosis #neurodegenerative #diseases #multiple_sclerosis ( #MS)

Ellorarxine, an agonist of the retinoic acid receptor, exhibits therapeutic potential for ALS and other neurodegenerative diseases. In neuroblastoma-spinal cord-34 (NSC-34), ellorarxine exerted neuroprotective effects mediated through (i) regulating excitotoxicity, (ii) restoring proteasome activity, (iii) reducing stress granule formation and (iv) modulating apoptosis pathways. In mice, ellorarxine preferentially accumulated in the central nervous system, particularly in the spinal cord, where induced gene expression associated with neuroprotection and neuroinflammation was observed. LEARN MORE in the Frontiers in Neuroscience GO TO https://lnkd.in/dCs-cmqD THIS ARTICLE IS PART OF THE RESEARCH TOPIC Brain Aging, Neurodegeneration, and the Role of Natural Molecules in Maintaining Brain Health https://lnkd.in/ddUDHKDu #ellorarxine, #ALS, #retinoic, #neuroprotection, #neuroinflammantion #proteasome, #excitotoxicity

🌟 Groundbreaking Discovery in Neuroimmunology! 🌟 Recent research has unveiled unique brain macrophages, specifically extrasinusoidal dural macrophages, that play a pivotal role in the central nervous system's response to neuroinflammation. 🔍 Key Findings: - These macrophages have distinct origins and gene expression profiles, setting them apart from other CNS macrophage populations. - They are crucial during autoimmune neuroinflammation, actively clearing apoptotic granulocytes and helping maintain homeostasis. This discovery not only enhances our understanding of the brain's innate immune system but also opens new avenues for therapeutic interventions in neuroinflammatory diseases like multiple sclerosis. 💡 By targeting these specialized cells, we could improve clearance of harmful cells and reduce inflammation—leading to better outcomes for patients. Dive deeper into this fascinating study to explore how it could revolutionize treatment strategies! Click the link for more insights. #AutoimmuneDisorders #CNSHealth #Macrophages #Neuroimmunology #Neuroinflammation #Publications #Research #MarketAccess #MarketAccessToday

📢 Review Sharing-Vol. 29 No. 1 💕 Title: Polycystic Ovary Syndrome Pathophysiology: Integrating Systemic, CNS and Circadian Processes 🤵 Authors: George Anderson,* 🔔 Full Text: https://lnkd.in/gfpzsFPm 🔑 Keywords: polycystic ovary syndrome; depression; gut microbiome; melatonin; N-acetylserotonin; aryl hydrocarbon receptor; kynurenine; tanycytes; paraventricular nucleus; adipocytes; treatment; tyrosine kinase receptor B 😎Welcome to your reading! #Bioscience #biomedicalscience #biochem #medicalscience #ScienceCommunication #Biochemistry #StemCell #Virology #CancerResearch #immunology #Genetics #MolecularBiology #Microbiology #medicine #health #CellularHealth #CellCancer