Steven M Wellman, Olivia A Coyne, Madeline M Douglas, Takashi D Y Kozai
{"title":"Aberrant accumulation of age- and disease-associated factors following neural probe implantation in a mouse model of Alzheimer's disease.","authors":"Steven M Wellman, Olivia A Coyne, Madeline M Douglas, Takashi D Y Kozai","doi":"10.1088/1741-2552/aceca5","DOIUrl":null,"url":null,"abstract":"<p><p><i>Objective</i>. Electrical stimulation has had a profound impact on our current understanding of nervous system physiology and provided viable clinical options for addressing neurological dysfunction within the brain. Unfortunately, the brain's immune suppression of indwelling microelectrodes currently presents a major roadblock in the long-term application of neural recording and stimulating devices. In some ways, brain trauma induced by penetrating microelectrodes produces similar neuropathology as debilitating brain diseases, such as Alzheimer's disease (AD), while also suffering from end-stage neuron loss and tissue degeneration. The goal of the present study was to understand whether there may be any parallel mechanisms at play between brain injury from chronic microelectrode implantation and those of neurodegenerative disorder.<i>Approach</i>. We used two-photon microscopy to visualize the accumulation, if any, of age- and disease-associated factors around chronically implanted electrodes in both young and aged mouse models of AD.<i>Main results</i>. We determined that electrode injury leads to aberrant accumulation of lipofuscin, an age-related pigment, in wild-type and AD mice alike. Furthermore, we reveal that chronic microelectrode implantation reduces the growth of pre-existing Alzheimer's plaques while simultaneously elevating amyloid burden at the electrode-tissue interface. Lastly, we uncover novel spatial and temporal patterns of glial reactivity, axonal and myelin pathology, and neurodegeneration related to neurodegenerative disease around chronically implanted microelectrodes.<i>Significance</i>. This study offers multiple novel perspectives on the possible neurodegenerative mechanisms afflicting chronic brain implants, spurring new potential avenues of neuroscience investigation and design of more targeted therapies for improving neural device biocompatibility and treatment of degenerative brain disease.</p>","PeriodicalId":16753,"journal":{"name":"Journal of neural engineering","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10594264/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neural engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1088/1741-2552/aceca5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Objective. Electrical stimulation has had a profound impact on our current understanding of nervous system physiology and provided viable clinical options for addressing neurological dysfunction within the brain. Unfortunately, the brain's immune suppression of indwelling microelectrodes currently presents a major roadblock in the long-term application of neural recording and stimulating devices. In some ways, brain trauma induced by penetrating microelectrodes produces similar neuropathology as debilitating brain diseases, such as Alzheimer's disease (AD), while also suffering from end-stage neuron loss and tissue degeneration. The goal of the present study was to understand whether there may be any parallel mechanisms at play between brain injury from chronic microelectrode implantation and those of neurodegenerative disorder.Approach. We used two-photon microscopy to visualize the accumulation, if any, of age- and disease-associated factors around chronically implanted electrodes in both young and aged mouse models of AD.Main results. We determined that electrode injury leads to aberrant accumulation of lipofuscin, an age-related pigment, in wild-type and AD mice alike. Furthermore, we reveal that chronic microelectrode implantation reduces the growth of pre-existing Alzheimer's plaques while simultaneously elevating amyloid burden at the electrode-tissue interface. Lastly, we uncover novel spatial and temporal patterns of glial reactivity, axonal and myelin pathology, and neurodegeneration related to neurodegenerative disease around chronically implanted microelectrodes.Significance. This study offers multiple novel perspectives on the possible neurodegenerative mechanisms afflicting chronic brain implants, spurring new potential avenues of neuroscience investigation and design of more targeted therapies for improving neural device biocompatibility and treatment of degenerative brain disease.
期刊介绍:
The goal of Journal of Neural Engineering (JNE) is to act as a forum for the interdisciplinary field of neural engineering where neuroscientists, neurobiologists and engineers can publish their work in one periodical that bridges the gap between neuroscience and engineering. The journal publishes articles in the field of neural engineering at the molecular, cellular and systems levels.
The scope of the journal encompasses experimental, computational, theoretical, clinical and applied aspects of: Innovative neurotechnology; Brain-machine (computer) interface; Neural interfacing; Bioelectronic medicines; Neuromodulation; Neural prostheses; Neural control; Neuro-rehabilitation; Neurorobotics; Optical neural engineering; Neural circuits: artificial & biological; Neuromorphic engineering; Neural tissue regeneration; Neural signal processing; Theoretical and computational neuroscience; Systems neuroscience; Translational neuroscience; Neuroimaging.