Visualizing nerve cells has been fundamental for the systematic description of brain structure and function in humans and other species. Different approaches aimed to unravel the morphological features of neuron types and diversity. The inherent complexity of the human nervous tissue and the need for proper histological processing have made studying human dendrites and spines challenging in postmortem samples. In this study, we used Golgi data and open-source software for 3D image reconstruction of human neurons from the cortical amygdaloid nucleus to show different dendrites and pleomorphic spines at different angles. Procedures required minimal equipment and generated high-quality images for differently shaped cells. We used the "single-section" Golgi method adapted for the human brain to engender 3D reconstructed images of the neuronal cell body and the dendritic ramification by adopting a neuronal tracing procedure. In addition, we elaborated 3D reconstructions to visualize heterogeneous dendritic spines using a supervised machine learning-based algorithm for image segmentation. These tools provided an additional upgrade and enhanced visual display of information related to the spatial orientation of dendritic branches and for dendritic spines of varied sizes and shapes in these human subcortical neurons. This same approach can be adapted for other techniques, areas of the central or peripheral nervous system, and comparative analysis between species.
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http://dx.doi.org/10.1002/cne.25430 | DOI Listing |
Alzheimers Dement
December 2024
University of Michigan, Ann Arbor, MI, USA.
Background: Alzheimer's disease (AD) is the leading cause of dementia worldwide. The recent announcement that lecanemab, a monoclonal antibody targeting amyloid-b, can slow down cognitive decline in AD is a great step forward in the battle against the disease. However, the modest success achieved in the clinical trial speak to the need for developing additional pharmaceutical approaches to target other key features of AD.
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December 2024
Gladstone Institutes, UCSF, San Francisco, CA, USA.
Background: Cerebrovascular alterations and innate immune activation are key features of Alzheimer's disease (AD). However, the mechanisms that link blood-brain barrier disruption to neurodegeneration are poorly understood and well-defined druggable targets at the neurovascular interface are limited.
Method: By developing a multiomic and genetic loss-of-function pipeline, we reported the transcriptomic and global phosphoproteomic landscape of blood-induced microglia activation and the causal role for fibrin in induction of neurodegenerative genes and oxidative stress pathways in innate immune cells.
Alzheimers Dement
December 2024
First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
Background: Synaptic plasticity impairment plays a critical role in the pathogenesis of Alzheimer's disease (AD), Smad4, a central intracellular signal transmission mediator of transmission of transforming growth factor-β (TGF-β) signaling, plays a pivotal role in many biological processes, including cell differentiation, migration, apoptosis and tumorigenesis. Emerging evidence has demonstrated that Smad4 is also involved in the pathogenesis of AD. Once TGF-β signaling is stimulated, Smad4 interaction with Sp1 and Smad3 induces the transcriptional activation of APP.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
UNC Chapel Hill, Chapel Hill, NC, USA.
Background: In the last decade, we have demonstrated that the brain-enriched E3 ubiquitin ligase TRIM9 regulates cytoskeletal dynamics, membrane remodeling, and netrin-dependent signaling pathways in all stages of neuron development, including the maturation of dendritic spines and electrophysiological activity. Moreover, TRIM9 protein levels increase in the adult brain and are maintained throughout adulthood. In the adult mouse TRIM9 is enriched within the postsynaptic density (PSD), a proteinaceous rich region in the post synapse, containing neurotransmitter receptors, scaffolding proteins, and cytoskeletal elements.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Yale University, New Haven, CT, USA.
Background: Advances in Alzheimer's disease (AD) have revealed a novel fluid biomarker, tau phosphorylated at T217 (pT217-tau), in CSF and plasma, that predicts AD prior to cognitive deficits. Understanding the role of pT217-tau is important in assessing efficacy of novel treatments aimed at early-stage disease. However, it is unknown why pT217-tau is effective in predicting brain pathology, as little is known about early, soluble pT217-tau brain expression.
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