Cell-specific spatial profiling of targeted protein expression to characterize the impact of intracortical microelectrode implantation on neuronal health†

IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS
Lindsey N. Druschel, Niveda M. Kasthuri, Sydney S. Song, Jaime J. Wang, Allison Hess-Dunning, E. Ricky Chan and Jeffrey R. Capadona
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引用次数: 0

Abstract

Intracortical microelectrode arrays (MEAs) can record neuronal activity and advance brain-computer interface (BCI) devices. Implantation of the invasive MEA kills local neurons, which has been documented using immunohistochemistry (IHC). Neuronal nuclear protein (NeuN), a protein that lines the nuclei of exclusively neuronal cells, has been used as a marker for neuronal health and survival for decades in neuroscience and neural engineering. NeuN staining is often used to describe the neuronal response to intracortical microelectrode array (MEA) implantation. However, IHC is semiquantitative, relying on intensity readings rather than directly counting expressed proteins. To supplement previous IHC studies, we evaluated the expression of proteins representing different aspects of neuronal structure or function: microtubule-associated protein 2 (MAP2), neurofilament light (NfL), synaptophysin (SYP), myelin basic protein (MBP), and oligodendrocyte transcription factor 2 (OLIG2) following a neural injury caused by intracortical MEA implantation. Together, these five proteins evaluate the cytoskeletal structure, neurotransmitter release, and myelination of neurons. To fully evaluate neuronal health in NeuN-positive (NeuN+) regions, we only quantified protein expression in NeuN+ regions, making this the first-ever cell-specific spatial profiling evaluation of targeted proteins by multiplex immunochemistry following MEA implantation. We performed our protein quantification along with NeuN IHC to compare the results of the two techniques directly. We found that NeuN immunohistochemical analysis does not show the same trends as MAP2, NfL, SYP, MBP, and OLIG2 expression. Further, we found that all five quantified proteins show a decreased expression pattern that aligns more with historic intracortical MEA recording performance.

Abstract Image

细胞特异性靶向蛋白表达空间图谱,描述皮层内微电极植入对神经元健康的影响。
皮层内微电极阵列(MEA)可以记录神经元活动,并推动脑机接口(BCI)设备的发展。植入侵入性微电极阵列会杀死局部神经元,这一点已通过免疫组化(IHC)得到证实。神经元核蛋白(NeuN)是神经元细胞核内的一种蛋白质,几十年来一直被神经科学和神经工程学用作神经元健康和存活的标志物。NeuN 染色通常用于描述神经元对皮层内微电极阵列(MEA)植入的反应。然而,IHC 是半定量的,依赖于强度读数,而不是直接计算表达的蛋白质。为了补充之前的 IHC 研究,我们评估了代表神经元结构或功能不同方面的蛋白质的表达:微管相关蛋白 2 (MAP2)、神经丝光 (NfL)、突触素 (SYP)、髓鞘碱性蛋白 (MBP) 和少突胶质细胞转录因子 2 (OLIG2)。这五种蛋白质共同评估神经元的细胞骨架结构、神经递质释放和髓鞘化。为了全面评估 NeuN 阳性(NeuN+)区域的神经元健康状况,我们只对 NeuN+ 区域的蛋白质表达进行了量化,这也是首次在 MEA 植入后通过多重免疫化学方法对目标蛋白质进行细胞特异性空间谱分析评估。我们在进行蛋白定量的同时还进行了 NeuN IHC,以直接比较两种技术的结果。我们发现,NeuN 免疫组化分析与 MAP2、NfL、SYP、MBP 和 OLIG2 的表达趋势不同。此外,我们还发现,所有五种量化蛋白的表达均呈下降趋势,这与皮层内 MEA 记录的历史表现更为吻合。
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来源期刊
Journal of Materials Chemistry B
Journal of Materials Chemistry B MATERIALS SCIENCE, BIOMATERIALS-
CiteScore
11.50
自引率
4.30%
发文量
866
期刊介绍: Journal of Materials Chemistry A, B & C cover high quality studies across all fields of materials chemistry. The journals focus on those theoretical or experimental studies that report new understanding, applications, properties and synthesis of materials. Journal of Materials Chemistry A, B & C are separated by the intended application of the material studied. Broadly, applications in energy and sustainability are of interest to Journal of Materials Chemistry A, applications in biology and medicine are of interest to Journal of Materials Chemistry B, and applications in optical, magnetic and electronic devices are of interest to Journal of Materials Chemistry C.Journal of Materials Chemistry B is a Transformative Journal and Plan S compliant. Example topic areas within the scope of Journal of Materials Chemistry B are listed below. This list is neither exhaustive nor exclusive: Antifouling coatings Biocompatible materials Bioelectronics Bioimaging Biomimetics Biomineralisation Bionics Biosensors Diagnostics Drug delivery Gene delivery Immunobiology Nanomedicine Regenerative medicine & Tissue engineering Scaffolds Soft robotics Stem cells Therapeutic devices
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