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Autophagy01:27

Autophagy

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Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
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Related Experiment Video

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Rodent Behavioral Testing to Assess Functional Deficits Caused by Microelectrode Implantation in the Rat Motor Cortex
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Cell-specific alterations in autophagy-lysosomal activity near the chronically implanted microelectrodes.

Keying Chen1, Camila Garcia Padilla1, Kirill Kiselyov2

  • 1Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Center for Neural Basis of Cognition, Pittsburgh, PA, USA.

Biomaterials
|September 22, 2023
PubMed
Summary

Long-term microelectrode implantation causes brain tissue damage by impairing the autophagy-lysosomal pathway, leading to waste buildup. This study reveals deficits in cellular waste clearance near chronic implants.

Keywords:
Brain-computer interfaceGlial reactivityNeuron survivalTissue homeostasisbrain metabolism

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Biomedical Engineering

Background:

  • Intracortical microelectrodes are vital for neuroscience research and clinical use.
  • Long-term implantation causes neurodegeneration and impaired recording performance.
  • Autophagy-lysosomal pathway dysfunction is linked to neurodegenerative diseases.

Purpose of the Study:

  • To investigate the impact of chronic microelectrode implantation on the autophagy-lysosomal pathway.
  • To characterize the spatiotemporal changes in autophagy-lysosomal activity near implants.
  • To understand the cellular mechanisms underlying implantation-induced brain tissue degeneration.

Main Methods:

  • Two-photon microscopy
  • Immunohistology
  • Spatiotemporal analysis of autophagy-lysosomal markers

Main Results:

  • Aberrant accumulation of immature autophagy vesicles near chronic implants.
  • Deficits in autophagy-lysosomal clearance, cargo accumulation, and reduced lysosomal protease levels.
  • Reactive astrocytes exhibit myelin-containing lysosomes post-implantation.

Conclusions:

  • Chronic microelectrode implantation impairs the brain's intracellular waste degradation system.
  • Autophagy-lysosomal pathway dysfunction contributes to tissue degeneration around implants.
  • Understanding these mechanisms is crucial for improving long-term neural interface performance.