Chapter 11 Autophagy in Neurite Injury and Neurodegeneration. In Vitro and In Vivo Models

Charleen T. Chu, Edward D. Plowey, Ruben K. Dagda, Robert W. Hickey, Salvatore J. Cherra, Robert S.B. Clark

Research output: Contribution to journalReview articlepeer-review

98 Scopus citations

Abstract

Recent advances indicate that maintaining a balanced level of autophagy is critically important for neuronal health and function. Pathologic dysregulation of macroautophagy has been implicated in synaptic dysfunction, cellular stress, and neuronal cell death. Autophagosomes and autolysosomes are induced in acute and chronic neurological disorders including stroke, brain trauma, neurotoxin injury, Parkinson's, Alzheimer's, Huntington's, motor neuron, prion, lysosomal storage, and other neurodegenerative diseases. Compared to other cell types, neuronal autophagy research presents particular challenges that may be addressed through still evolving techniques. Neuronal function depends upon maintenance of axons and dendrites (collectively known as neurites) that extend for great distances from the cell body. Both autophagy and mitochondrial content have been implicated in regulation of neurite length and function in physiological (plasticity) and pathological remodeling. Here, we highlight several molecular cell biological and imaging methods to study autophagy and mitophagy in neuritic and somatic compartments of differentiated neuronal cell lines and primary neuron cultures, using protocols developed in toxic and genetic models of parkinsonian neurodegeneration. In addition, mature neurons can be studied using in vivo protocols for modeling ischemic and traumatic injuries. Future challenges include application of automated computer-assisted image analysis to the axodendritic tree of individual neurons and improving methods for measuring neuronal autophagic flux.

Original languageEnglish
Pages (from-to)217-249
Number of pages33
JournalMethods in Enzymology
Volume453
Issue numberC
DOIs
StatePublished - 2009

Bibliographical note

Funding Information:
We thank Jason Callio for technical assistance and maintenance of transgenic mouse colonies. The authors are supported by funding from the National Institutes of Health (R01 AG026389, R21 NS053777, K18 DC009120 to CTC; F32 AG030821 to RKD; K08 HD040848 to RWH; R01 NS038620 to RSBC).

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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