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Title: Cell-specific alterations in autophagy-lysosomal activity near the chronically implanted microelectrodes
Intracortical microelectrodes that can record and stimulate brain activity have become a valuable technique for basic science research and clinical applications. However, long-term implantation of these microelectrodes can lead to progressive neurodegeneration in the surrounding microenvironment, characterized by elevation in disease-associated markers. Dysregulation of autophagy-lysosomal degradation, a major intracellular waste removal process, is considered a key factor in the onset and progression of neurodegenerative diseases. It is plausible that similar dysfunctions in autophagy-lysosomal degradation contribute to tissue degeneration following implantation-induced focal brain injury, ultimately impacting recording performance. To understand how the focal, persistent brain injury caused by long-term microelectrode implantation impairs autophagylysosomal pathway, we employed two-photon microscopy and immunohistology. This investigation focused on the spatiotemporal characterization of autophagy-lysosomal activity near the chronically implanted microelectrode. We observed an aberrant accumulation of immature autophagy vesicles near the microelectrode over the chronic implantation period. Additionally, we found deficits in autophagy-lysosomal clearance proximal to the chronic implant, which was associated with an accumulation of autophagy cargo and a reduction in lysosomal protease level during the chronic period. Furthermore, our evidence demonstrates reactive astrocytes have myelin-containing lysosomes near the microelectrode, suggesting its role of myelin engulfment during acute implantation period. Together, this study sheds light on the process of brain tissue degeneration caused by longterm microelectrode implantation, with a specific focus on impaired intracellular waste degradation.  more » « less
Award ID(s):
1943906
PAR ID:
10503023
Author(s) / Creator(s):
; ; ;
Publisher / Repository:
Elsevier
Date Published:
Journal Name:
Biomaterials
Volume:
302
Issue:
C
ISSN:
0142-9612
Page Range / eLocation ID:
122316
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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