Activated microglia are an important feature of many neurological diseases and can be imaged in vivo using 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK11195), a ligand that binds the peripheral benzodiazepine receptor (PBR). N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl) acetamide (DAA1106) is a new PBR-specific ligand that has been reported to bind to PBR with higher affinity compared with PK11195. We hypothesized that this high-affinity binding of DAA1106 to PBR will enable better delineation of microglia in vivo using positron emission tomography. [(3)H]DAA1106 showed higher binding affinity compared with [(3)H](R)-PK11195 in brain tissue derived from normal rats and the rats injected intrastriatally with 6-hydroxydopamine or lipopolysaccharide at the site of the lesion. Immunohistochemistry combined with autoradiography in brain tissues as well as correlation analyses showed that increased [(3)H]DAA1106 binding corresponded mainly to activated microglia. Finally, ex vivo autoradiography and positron emission tomography imaging in vivo showed greater retention of [(11)C]DAA1106 compared with [(11)C](R)-PK11195 in animals injected with either lipopolysaccaride or 6-hydroxydopamine at the site of lesion. These results indicate that DAA1106 binds with higher affinity to microglia in rat models of neuroinflammation when compared with PK11195, suggesting that [(11)C]DAA1106 may represent a significant improvement over [(11)C](R)-PK11195 for in vivo imaging of activated microglia in human neuroinflammatory disorders.
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http://dx.doi.org/10.1111/j.1471-4159.2007.04690.x | DOI Listing |
Mol Med
January 2025
Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.
Background: Chronic rhinosinusitis (CRS) is a global health issue, with some patients experiencing anxiety and depression-like symptoms. This study investigates the role of HMGB1 in anxiety and depression-like behaviors associated with the microglial Notch1/Hes-1 pathway in CRS mice.
Methods: A CRS mouse model was developed, and behavioral assessments were conducted to evaluate anxiety and depression-like behaviors.
Neurobiol Dis
January 2025
Institute of Physiology, Medical University of Innsbruck, Innsbruck, Austria. Electronic address:
Background: Fabry disease (FD) patients are known to be at high risk of developing neuropsychiatric symptoms such as anxiety, depression and cognitive deficits. Despite this, they are underdiagnosed and inadequately treated. It is unknown whether these symptoms arise from pathological glycosphingolipid deposits or from cerebrovascular abnormalities affecting neuronal functions in the central nervous system.
View Article and Find Full Text PDFBiomaterials
January 2025
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States; Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, United States. Electronic address:
Intracortical microelectrodes (IMEs) are essential for neural signal acquisition in neuroscience and brain-machine interface (BMI) systems, aiding patients with neurological disorders, paralysis, and amputations. However, IMEs often fail to maintain robust signal quality over time, partly due to neuroinflammation caused by vascular damage during insertion. Platelet-inspired nanoparticles (PIN), which possess injury-targeting functions, mimic the adhesion and aggregation of active platelets through conjugated collagen-binding peptides (CBP), von Willebrand Factor-binding peptides (VBP), and fibrinogen-mimetic peptides (FMP).
View Article and Find Full Text PDFCell Rep
January 2025
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan. Electronic address:
Proteasomes generate antigenic peptides presented on cell surfaces-a process that, in neuroglia, is highly responsive to external stimuli. However, the function of the self-antigens presented by CNS parenchymal cells remains unclear. Here, we report that the fidelity of neuroglial self-antigens is crucial to suppress encephalitogenic T cell responses by elevating regulatory T (Treg) cell populations.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
All India Institute of Medical Sciences, AIIMS, New Delhi, Delhi, India.
Background: Alzheimer's disease (AD) is a progressive brain disorder which leads to gradual decline in memory, thinking, behaviour and social skills. The current scenario for drug development is based on neuro-inflammation and oxidative stress. Amyloid-β (Aβ) deposition, a major hallmark of the disease activates microglia leading to neuro-inflammation and neuro-degeneration induced by activation of COX-2 via NFkB p50 in glioblastoma cells.
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