PMID- 28621662
OWN - NLM
STAT- MEDLINE
DCOM- 20180312
LR  - 20181113
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 6
DP  - 2017 Jun 16
TI  - Chronic lithium treatment elicits its antimanic effects via BDNF-TrkB dependent 
      synaptic downscaling.
LID - e25480 [pii]
LID - 10.7554/eLife.25480 [doi]
AB  - Lithium is widely used as a treatment for Bipolar Disorder although the molecular 
      mechanisms that underlie its therapeutic effects are under debate. In this study, 
      we show brain-derived neurotrophic factor (BDNF) is required for the 
      antimanic-like effects of lithium but not the antidepressant-like effects in 
      mice. We performed whole cell patch clamp recordings of hippocampal neurons to 
      determine the impact of lithium on synaptic transmission that may underlie the 
      behavioral effects. Lithium produced a significant decrease in 
      alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated 
      miniature excitatory postsynaptic current (mEPSC) amplitudes due to postsynaptic 
      homeostatic plasticity that was dependent on BDNF and its receptor tropomyosin 
      receptor kinase B (TrkB). The decrease in AMPAR function was due to reduced 
      surface expression of GluA1 subunits through dynamin-dependent endocytosis. 
      Collectively, these findings demonstrate a requirement for BDNF in the antimanic 
      action of lithium and identify enhanced dynamin-dependent endocytosis of AMPARs 
      as a potential mechanism underlying the therapeutic effects of lithium.
FAU - Gideons, Erinn S
AU  - Gideons ES
AUID- ORCID: 0000-0003-4778-3869
AD  - Department of Neuroscience, UT Southwestern Medical Center, Dallas, United 
      States.
FAU - Lin, Pei-Yi
AU  - Lin PY
AUID- ORCID: 0000-0001-7447-3212
AD  - Department of Neuroscience, UT Southwestern Medical Center, Dallas, United 
      States.
FAU - Mahgoub, Melissa
AU  - Mahgoub M
AUID- ORCID: 0000-0003-1491-4439
AD  - Department of Neuroscience, UT Southwestern Medical Center, Dallas, United 
      States.
FAU - Kavalali, Ege T
AU  - Kavalali ET
AUID- ORCID: 0000-0003-1777-227X
AD  - Department of Neuroscience, UT Southwestern Medical Center, Dallas, United 
      States.
FAU - Monteggia, Lisa M
AU  - Monteggia LM
AUID- ORCID: 0000-0003-0018-501X
AD  - Department of Neuroscience, UT Southwestern Medical Center, Dallas, United 
      States.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170616
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Antimanic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptors, Glutamate)
RN  - 9FN79X2M3F (Lithium)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Antimanic Agents/*administration & dosage/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Hippocampus/physiology
MH  - Lithium/*administration & dosage/*pharmacology
MH  - Mice, Inbred C57BL
MH  - Neurons/*drug effects/physiology
MH  - Patch-Clamp Techniques
MH  - Receptor, trkB/*metabolism
MH  - Receptors, Glutamate/drug effects/metabolism
MH  - Synaptic Transmission/drug effects
PMC - PMC5499943
OTO - NOTNLM
OT  - bdnf
OT  - dynamin
OT  - endocytosis
OT  - lithium
OT  - mania
OT  - mouse
OT  - neuroscience
COIS- The authors declare that no competing interests exist.
EDAT- 2017/06/18 06:00
MHDA- 2018/03/13 06:00
PMCR- 2017/06/17
CRDT- 2017/06/17 06:00
PHST- 2017/01/26 00:00 [received]
PHST- 2017/06/07 00:00 [accepted]
PHST- 2017/06/18 06:00 [pubmed]
PHST- 2018/03/13 06:00 [medline]
PHST- 2017/06/17 06:00 [entrez]
PHST- 2017/06/17 00:00 [pmc-release]
AID - e25480 [pii]
AID - 25480 [pii]
AID - 10.7554/eLife.25480 [doi]
PST - epublish
SO  - Elife. 2017 Jun 16;6:e25480. doi: 10.7554/eLife.25480.