Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Autophagy. 2010 Aug;6(6):702-10. Epub 2010 Aug 14.

Short-term fasting induces profound neuronal autophagy.

Author information

  • 1Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.

Abstract

Disruption of autophagy--a key homeostatic process in which cytosolic components are degraded and recycled through lysosomes--can cause neurodegeneration in tissue culture and in vivo. Upregulation of this pathway may be neuroprotective, and much effort is being invested in developing drugs that cross the blood brain barrier and increase neuronal autophagy. One well-recognized way of inducing autophagy is by food restriction, which upregulates autophagy in many organs including the liver; but current dogma holds that the brain escapes this effect, perhaps because it is a metabolically privileged site. Here, we have re-evaluated this tenet using a novel approach that allows us to detect, enumerate and characterize autophagosomes in vivo. We first validate the approach by showing that it allows the identification and characterization of autophagosomes in the livers of food-restricted mice. We use the method to identify constitutive autophagosomes in cortical neurons and Purkinje cells, and we show that short-term fasting leads to a dramatic upregulation in neuronal autophagy. The increased neuronal autophagy is revealed by changes in autophagosome abundance and characteristics, and by diminished neuronal mTOR activity in vivo, demonstrated by a reduction in levels of phosphorylated S6 ribosomal protein in Purkinje cells. The increased abundance of autophagosomes in Purkinje cells was confirmed using transmission electron microscopy. Our data lead us to speculate that sporadic fasting might represent a simple, safe and inexpensive means to promote this potentially therapeutic neuronal response.

PMID:
20534972
[PubMed - indexed for MEDLINE]
PMCID:
PMC3106288
Free PMC Article

Images from this publication.See all images (4)Free text

Figure 1
Figure 2
Figure 3
Figure 4
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Landes Bioscience Icon for PubMed Central
    Loading ...
    Write to the Help Desk