PMID- 29104031
OWN - NLM
STAT- MEDLINE
DCOM- 20180710
LR  - 20211204
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 367
DP  - 2017 Dec 26
TI  - Rapamycin-Sensitive Late-LTP is Enhanced in the Hippocampus of IL-6 Transgenic 
      Mice.
PG  - 200-210
LID - S0306-4522(17)30777-7 [pii]
LID - 10.1016/j.neuroscience.2017.10.040 [doi]
AB  - The neuroimmune factor IL-6 has been shown to regulate hippocampal long-term 
      potentiation (LTP), an activity-dependent enhancement of synaptic transmission 
      that plays a central role in memory and learning. This IL-6 action was 
      demonstrated with relatively short IL-6 exposure, and may reflect physiological 
      actions of IL-6. IL-6 is also expressed chronically at elevated levels in the 
      central nervous system (CNS) under pathological conditions such as neurological 
      disorders. Little is known about the effects IL-6 on LTP under such conditions, 
      an issue that we are addressing by electrophysiological recordings from CA1 
      pyramidal neurons of hippocampal slices from transgenic mice that persistently 
      express elevated levels of IL-6 in the CNS (IL-6 tg). The current studies 
      examined the long-lasting phase of LTP (late LTP; L-LTP) and the potential 
      involvement mammalian target of rapamycin (mTOR), a known regulator of L-LTP and 
      a downstream partner of IL-6 signal transduction pathways. Results show that 
      basal synaptic transmission and L-LTP were increased in hippocampal slices from 
      IL-6 tg mice compared to slices from non-transgenic (non-tg) control mice. An 
      inhibitor of mTOR, rapamycin, reduced L-LTP in slices from both genotypes, and 
      eliminated the difference in magnitude of L-LTP between IL-6 and non-tg 
      hippocampus. There were no genotypic effect of rapamycin on basal synaptic 
      transmission, but synaptic responses during the LTP induction protocol were 
      reduced in IL-6 tg slices, an effect that could contribute to the reduction of 
      L-LTP in the IL-6 tg slices. These results indicate that persistently increased 
      levels of IL-6 can lead to alterations in mTOR regulation of L-LTP, possibly 
      affecting learning and memory.
CI  - Copyright (c) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Olde Engberink, Anneke
AU  - Olde Engberink A
AD  - Neuroscience Department, The Scripps Research Institute, San Diego, USA; 
      Department of Translational Neuroscience, Brain Center Rudolf Magnus, UMC 
      Utrecht, Utrecht, Netherlands.
FAU - Hernandez, Ruben
AU  - Hernandez R
AD  - Neuroscience Department, The Scripps Research Institute, San Diego, USA.
FAU - de Graan, Pierre
AU  - de Graan P
AD  - Department of Translational Neuroscience, Brain Center Rudolf Magnus, UMC 
      Utrecht, Utrecht, Netherlands.
FAU - Gruol, Donna L
AU  - Gruol DL
AD  - Neuroscience Department, The Scripps Research Institute, San Diego, USA. 
      Electronic address: gruol@scripps.edu.
LA  - eng
GR  - R01 AA024484/AA/NIAAA NIH HHS/United States
GR  - RC1 AA019261/AA/NIAAA NIH HHS/United States
PT  - Journal Article
DEP - 20171110
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-6)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Electric Stimulation
MH  - Female
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Hippocampus/*cytology/drug effects
MH  - Immunosuppressive Agents/*pharmacology
MH  - In Vitro Techniques
MH  - Interleukin-6/genetics/*metabolism
MH  - Long-Term Potentiation/*drug effects/genetics
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Neurons/*drug effects
MH  - Sirolimus/*pharmacology
MH  - Statistics, Nonparametric
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Time Factors
PMC - PMC5728701
MID - NIHMS922046
OTO - NOTNLM
OT  - astrocyte
OT  - cytokine
OT  - mTOR
OT  - neuroimmune
OT  - synaptic function
OT  - synaptic plasticity
COIS- Conflict of interest statement: The authors declare no conflict of interest.
EDAT- 2017/11/07 06:00
MHDA- 2018/07/11 06:00
PMCR- 2018/12/26
CRDT- 2017/11/07 06:00
PHST- 2017/07/27 00:00 [received]
PHST- 2017/10/07 00:00 [revised]
PHST- 2017/10/27 00:00 [accepted]
PHST- 2017/11/07 06:00 [pubmed]
PHST- 2018/07/11 06:00 [medline]
PHST- 2017/11/07 06:00 [entrez]
PHST- 2018/12/26 00:00 [pmc-release]
AID - S0306-4522(17)30777-7 [pii]
AID - 10.1016/j.neuroscience.2017.10.040 [doi]
PST - ppublish
SO  - Neuroscience. 2017 Dec 26;367:200-210. doi: 10.1016/j.neuroscience.2017.10.040. 
      Epub 2017 Nov 10.