A morphometric study of the basal nucleus of Meynert (bnM) has been performed in a 70-year-old man with a 4-year history of pathologically confirmed progressive supranuclear palsy (PSP). An important neuronal loss (52%) was demonstrated in the bnM. This finding has not been previously documented with morphometric methods in PSP, but the involvement of the bnM is well known in other related conditions, i.e., Parkinson's disease, Alzheimer's disease, and Parkinson-dementia complex of Guam. Our findings yield support to the view that the involvement of the bnM, a nucleus with complex connections with various subcortical structures and diffuse cholinergic projections on the neocortex, could play an important role in the physiopatholog of subcortical dementia.
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http://dx.doi.org/10.1007/BF00697397 | DOI Listing |
Front Neurosci
December 2024
Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital of Bonn, University of Bonn, Bonn, Germany.
Brain aging is a chronic process linked to inflammation, microglial activation, and oxidative damage, which can ultimately lead to neuronal loss. Sialic acid-binding immunoglobulin-like lectin-11 (SIGLEC-11) is a human lineage-specific microglial cell surface receptor that recognizes -2-8-linked oligo-/polysialylated glycomolecules with inhibitory effects on the microglial inflammatory pathways. Recently, the gene locus was prioritized as a top tier microglial gene with potential causality to Alzheimer's disease, although its role in inflammation and neurodegeneration remains poorly understood.
View Article and Find Full Text PDFThe transmembrane protein Synapse Differentiation Induced Gene 4 (SynDIG4) functions as an auxiliary factor of AMPA receptors (AMPARs) and plays a critical role in excitatory synapse plasticity as well as hippocampal-dependent learning and memory. Mice lacking SynDIG4 have reduced surface expression of GluA1 and GluA2 and are impaired in single tetanus-induced long-term potentiation and NMDA receptor (NMDAR)-dependent long-term depression. These findings suggest that SynDIG4 may play an important role in regulating AMPAR distribution through intracellular trafficking mechanisms; however, the precise roles by which SynDIG4 governs AMPAR distribution remain unclear.
View Article and Find Full Text PDFThe current state of mental health treatment for individuals diagnosed with major depressive disorder leaves billions of individuals with first-line therapies that are ineffective or burdened with undesirable side effects. One major obstacle is that distinct pathologies may currently be diagnosed as the same disease and prescribed the same treatments. The key to developing antidepressants with ubiquitous efficacy is to first identify a strategy to differentiate between heterogeneous conditions.
View Article and Find Full Text PDFMutations in the gene cause the most common form of human hereditary hearing loss, known as DFNB1. is expressed in two cell groups of the cochlea-epithelial cells of the organ of Corti and fibrocytes of the inner sulcus and lateral wall-but not by sensory hair cells or neurons. Attempts to treat mouse models of DFNB1 with AAV vectors mediating nonspecific expression have not substantially restored function, perhaps because inappropriate expression in hair cells and neurons could compromise their electrical activity.
View Article and Find Full Text PDFRetinopathy of prematurity (ROP) and diabetic retinopathy (DR) are ocular disorders in which a loss of retinal vasculature leads to ischemia followed by a compensatory neovascularization response. In mice, this is modeled using oxygen-induced retinopathy (OIR), whereby neonatal animals are transiently housed under hyperoxic conditions that result in central retina vessel regression and subsequent neovascularization. Using endothelial cell (EC)-specific gene deletion, we found that loss of two ETS-family transcription factors, ERG and FLI1, led to regression of OIR-induced neovascular vessels but failed to improve visual function, suggesting that relevant retinal damage occurs prior to and independently of neovascularization.
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