The biological response to electrodes implanted in the brain has been a long-standing barrier to achieving a stable tissue device-interface. Understanding the mechanisms underlying this response could explain phenomena including recording instability and loss, shifting stimulation thresholds, off-target effects of neuromodulation, and stimulation-induced depression of neural excitability. Our prior work detected differential expression in hundreds of genes following device implantation. Here, we extend upon that work by providing new analyses using differential co-expression analysis, which identifies changes in the correlation structure between groups of genes detected at the interface in comparison to control tissues. We used an "eigengene" approach to identify hub genes associated with each module. Our work adds to a growing body of literature which applies new techniques in molecular biology and computational analysis to long-standing issues surrounding electrode integration with the brain.
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http://dx.doi.org/10.1109/EMBC48229.2022.9871437 | DOI Listing |
Alzheimers Dement
December 2024
David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder involving pathological deposition of tau that includes glial inclusions and specific regional vulnerability patterns. Therapeutic developments are hampered by incomplete understanding of disease mechanisms. Few studies have examined its cell type-specific effects.
View Article and Find Full Text PDFBackground: Single-nucleus RNA sequencing (snRNAseq) allows for the dissection of the cell type-specific transcriptional profiles of tissue specimens. In this study, we compared gene expression in multiple brain cell types in brain tissue from Alzheimer disease (AD) cases with no or other co-existing pathologies including Lewy body disease (LBD) and vascular disease (VaD).
Method: We evaluated differential gene expression measured from single nucleus RNA sequencing (snRNAseq) data generated from the hippocampus region tissue donated by 11 BU ADRC participants with neuropathologically confirmed AD with or without a co-existing pathology (AD-only = 3, AD+VaD = 6, AD+LBD = 2).
Alzheimers Dement
December 2024
Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
Background: Cerebral amyloid angiopathy (CAA), defined as the accumulation of amyloid in cerebral blood vessels causing alterations in the blood brain barrier (BBB) and the gliovascular unit, occurs in over 85% of Alzheimer's disease (AD) cases, positioning CAA as one of the strongest vascular contributors to age-related cognitive decline. However, the specific mechanisms in the microvasculature that become altered due to amyloid deposition and its downstream effects on the brain are complex and incompletely understood. A spatial transcriptomic analysis comparing pathways affected in the gliovascular niche differently in the presence of vascular amyloid could provide critical insight into the mechanisms underlying cerebrovascular changes involved in the deposition of Amyloid in the cerebrovasculature.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Exeter, Exeter, United Kingdom.
Background: The J20 mouse is an established model of amyloid pathology, exhibiting neuropathological and behavioural symptoms reflective of human Alzheimer's disease (AD). Previous work, conducted by Castanho et al (2020), revealed transcriptomic change in the hippocampus of J20 mice to be associated with the accumulation of amyloid pathology. Here, we investigated the spatial distribution of such transcriptomic changes using novel spatial transcriptomic technology.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Institute for Memory Impairments and Neurological Disorders (MIND), Irvine, CA, USA.
Background: Alzheimer's Disease (AD) presents a significant challenge in understanding its complex pathophysiology, owing to its multifaceted genetic and environmental factors. Despite extensive research, the translatability of findings from animal models to human conditions remains a critical hurdle. This study addresses the need to uncover shared molecular changes in AD by comparing human and mouse models, thereby enhancing our understanding of the disease's underlying mechanisms and improving the prospects for effective treatments.
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