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Review
. 2010 Oct;1802(10):918-23.
doi: 10.1016/j.bbadis.2009.10.010. Epub 2009 Oct 30.

Evaluation of autophagy using mouse models of brain injury

Alicia K Au  1 , Hülya Bayir, Patrick M Kochanek, Robert S B Clark
Affiliations
Review

Evaluation of autophagy using mouse models of brain injury

Alicia K Au et al. Biochim Biophys Acta. 2010 Oct.

Abstract

Autophagy is a homeostatic, carefully regulated, and dynamic process for intracellular recycling of bulk proteins, aging organelles, and lipids. Autophagy occurs in all tissues and cell types, including the brain and neurons. Alteration in the dynamics of autophagy has been observed in many diseases of the central nervous system. Disruption of autophagy for an extended period of time results in accumulation of unwanted proteins and neurodegeneration. However, the role of enhanced autophagy after acute brain injury remains undefined. Established mouse models of brain injury will be valuable in clarifying the role of autophagy after brain injury and are the topic of discussion in this review.

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Figures

Fig. 1
Fig. 1
A. Simplified schematic of starvation- and non-starvation-induced autophagy. Putative effectors of autophagy are highlighted in white boxes. B. Electron micrograph showing autophagosomes (t he “gold standard” for detection of autophagy) in an axons after traumatic brain injury in mice (bar = 100 nm). Abbreviations: 3-MA, 3-methyladenine; Atg, autophagy complex component; ERK, extracellular signal regulated protein kinase; GAIP, Gα-interacting protein; GCEE, γ-glutamyl cysteine-ethyl ester; LC3, light chain 3; MEK, mitogen activated protein kinase/ERK; mTOR, mammalian target of rapamycin; P, phosphate; PE, phosphatidylethanolamine; PI3K, phosphoinositide 3-kinase; PKB, protein kinase B; U0126, 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene.
Fig. 2
Fig. 2
Dynamic tracking of autophagy in primary cortical neurons in vitro. A. Discrimination of GFP-LC3+/− mice using fluorescent macroscopy. B. Identification of GFP-LC3-enriched vesicles suggestive of autophagosomes in primary cortical neurons from GFP-LC3+/− mice after 24 hours of nutrient deprivation using fluorescent microscopy. C. Dynamic tracking of mitophagy in primary cortical neurons from GFP-LC3+/− mice using time-lapsed microscopy. Autophagosomes (green) fusing with mitochondria (red; MitoTracker Red, Invitrogen, Carlsbad, CA) are highlighted by arrows. Time stamp is hours:minutes.
Fig. 3
Fig. 3
Hypothetical schematic illustrating potential dual-roles of autophagy after critical brain injury.
See this image and copyright information in PMC

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