Chronic lithium treatment elicits its antimanic effects via BDNF-TrkB dependent synaptic downscaling
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 e...
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doaj-f2a90f3d9a95405aaf348bb2ac3b88732021-05-05T13:32:47ZengeLife Sciences Publications LtdeLife2050-084X2017-06-01610.7554/eLife.25480Chronic lithium treatment elicits its antimanic effects via BDNF-TrkB dependent synaptic downscalingErinn S Gideons0https://orcid.org/0000-0003-4778-3869Pei-Yi Lin1https://orcid.org/0000-0001-7447-3212Melissa Mahgoub2https://orcid.org/0000-0003-1491-4439Ege T Kavalali3https://orcid.org/0000-0003-1777-227XLisa M Monteggia4https://orcid.org/0000-0003-0018-501XDepartment of Neuroscience, UT Southwestern Medical Center, Dallas, United StatesDepartment of Neuroscience, UT Southwestern Medical Center, Dallas, United StatesDepartment of Neuroscience, UT Southwestern Medical Center, Dallas, United StatesDepartment of Neuroscience, UT Southwestern Medical Center, Dallas, United StatesDepartment of Neuroscience, UT Southwestern Medical Center, Dallas, United StatesLithium 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 α-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.https://elifesciences.org/articles/25480lithiumbdnfdynaminendocytosismania |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Erinn S Gideons Pei-Yi Lin Melissa Mahgoub Ege T Kavalali Lisa M Monteggia |
spellingShingle |
Erinn S Gideons Pei-Yi Lin Melissa Mahgoub Ege T Kavalali Lisa M Monteggia Chronic lithium treatment elicits its antimanic effects via BDNF-TrkB dependent synaptic downscaling eLife lithium bdnf dynamin endocytosis mania |
author_facet |
Erinn S Gideons Pei-Yi Lin Melissa Mahgoub Ege T Kavalali Lisa M Monteggia |
author_sort |
Erinn S Gideons |
title |
Chronic lithium treatment elicits its antimanic effects via BDNF-TrkB dependent synaptic downscaling |
title_short |
Chronic lithium treatment elicits its antimanic effects via BDNF-TrkB dependent synaptic downscaling |
title_full |
Chronic lithium treatment elicits its antimanic effects via BDNF-TrkB dependent synaptic downscaling |
title_fullStr |
Chronic lithium treatment elicits its antimanic effects via BDNF-TrkB dependent synaptic downscaling |
title_full_unstemmed |
Chronic lithium treatment elicits its antimanic effects via BDNF-TrkB dependent synaptic downscaling |
title_sort |
chronic lithium treatment elicits its antimanic effects via bdnf-trkb dependent synaptic downscaling |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2017-06-01 |
description |
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 α-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. |
topic |
lithium bdnf dynamin endocytosis mania |
url |
https://elifesciences.org/articles/25480 |
work_keys_str_mv |
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1721461600186007552 |