Anavex Life Sciences Corp (AVXL)

[XenaLives]

Autophagy, BDNF and brain palsticity...

Highlights
-- Autophagy is differentially regulated by fasting in different
brain regions
-- BDNF signaling suppresses autophagy in the forebrain of
adult mice
-- BDNF ablation in the neural lineage causes uncontrolled
increase in autophagy
-- Increased autophagy mediates the synaptic defects caused
by BDNF deficiency

SUMMARY
Autophagy is crucial for neuronal integrity. Loss of key autophagic components leads to progressive neurodegeneration and structural defects in preand postsynaptic morphologies. However, the molecular mechanisms regulating autophagy in the brain remain elusive. Similarly, while it is widely accepted that protein turnover is required for synaptic plasticity, the contribution of autophagy to the degradation of synaptic proteins is unknown. Here, we report that BDNF signaling via the tropomyosin receptor kinase B (TrkB) and the phosphatidylinositol-30 kinase (PI3K)/Akt pathway suppresses autophagy in vivo. In addition, we demonstrate that suppression of autophagy is required for BDNFinduced synaptic plasticity and for memory enhancement under conditions of nutritional stress. Finally, we identify three key remodelers of postsynaptic densities as cargo of autophagy. Our results establish autophagy as a pivotal component of BDNF signaling, which is essential for BDNF-induced synaptic plasticity. This molecular mechanism underlies behavioral adaptations that increase fitness in times of scarcity.

https://www.cell.com/cell-metabolism/pdfExtended/S1550-4131(17)30347-9