PMID- 22836274
OWN - NLM
STAT- MEDLINE
DCOM- 20121029
LR  - 20211203
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 32
IP  - 30
DP  - 2012 Jul 25
TI  - Neuronal stimulation induces autophagy in hippocampal neurons that is involved in 
      AMPA receptor degradation after chemical long-term depression.
PG  - 10413-22
LID - 10.1523/JNEUROSCI.4533-11.2012 [doi]
AB  - Many studies have reported the roles played by regulated proteolysis in synaptic 
      plasticity and memory, but the role of autophagy in neurons remains unclear. In 
      mammalian cells, autophagy functions in the clearance of long-lived proteins and 
      organelles and in adaptation to starvation. In neurons, although 
      autophagy-related proteins (ATGs) are highly expressed, autophagic activity 
      markers, autophagosome (AP) number, and light chain protein 3-II (LC3-II) are low 
      compared with other cell types. In contrast, conditional knock-out of ATG5 or 
      ATG7 in mouse brain causes neurodegeneration and behavioral deficits. Therefore, 
      this study aimed to test whether autophagy is especially regulated in neurons to 
      adapt to brain functions. In cultured rat hippocampal neurons, we found that KCl 
      depolarization transiently increased LC3-II and AP number, which was partially 
      inhibited with APV, an NMDA receptor (NMDAR) inhibitor. Brief low-dose NMDA, a 
      model of chemical long-term depression (chem-LTD), increased LC3-II with a time 
      course coincident with Akt and mammalian target of rapamycin (mTOR) 
      dephosphorylation and degradation of GluR1, an AMPA receptor (AMPAR) subunit. 
      Downstream of NMDAR, the protein phosphatase 1 inhibitor okadaic acid, PTEN 
      inhibitor bpV(HOpic), autophagy inhibitor wortmannin, and short hairpin 
      RNA-mediated knockdown of ATG7 blocked chem-LTD-induced autophagy and partially 
      recovered GluR1 levels. After chem-LTD, GFP-LC3 puncta increased in spines and in 
      dendrites when AP-lysosome fusion was blocked. These results indicate that 
      neuronal stimulation induces NMDAR-dependent autophagy through PI3K-Akt-mTOR 
      pathway inhibition, which may function in AMPAR degradation, thus suggesting 
      autophagy as a contributor to NMDAR-dependent synaptic plasticity and brain 
      functions.
FAU - Shehata, Mohammad
AU  - Shehata M
AD  - Department of Biochemistry, Graduate School of Medicine and Pharmaceutical 
      Sciences, University of Toyama, Toyama 930-0194, Japan.
FAU - Matsumura, Hiroyuki
AU  - Matsumura H
FAU - Okubo-Suzuki, Reiko
AU  - Okubo-Suzuki R
FAU - Ohkawa, Noriaki
AU  - Ohkawa N
FAU - Inokuchi, Kaoru
AU  - Inokuchi K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Receptors, AMPA)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Autophagy/drug effects/*physiology
MH  - Cells, Cultured
MH  - Excitatory Amino Acid Agonists/pharmacology
MH  - Hippocampus/cytology/drug effects/*metabolism
MH  - Long-Term Synaptic Depression/drug effects/*physiology
MH  - Mice
MH  - N-Methylaspartate/pharmacology
MH  - Neurons/cytology/drug effects/*metabolism
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Receptors, AMPA/*metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC6703735
EDAT- 2012/07/28 06:00
MHDA- 2012/10/30 06:00
PMCR- 2013/01/25
CRDT- 2012/07/28 06:00
PHST- 2012/07/28 06:00 [entrez]
PHST- 2012/07/28 06:00 [pubmed]
PHST- 2012/10/30 06:00 [medline]
PHST- 2013/01/25 00:00 [pmc-release]
AID - 32/30/10413 [pii]
AID - 3789687 [pii]
AID - 10.1523/JNEUROSCI.4533-11.2012 [doi]
PST - ppublish
SO  - J Neurosci. 2012 Jul 25;32(30):10413-22. doi: 10.1523/JNEUROSCI.4533-11.2012.