PMID- 25204460
OWN - NLM
STAT- MEDLINE
DCOM- 20151117
LR  - 20211021
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 35
IP  - 2
DP  - 2015 Mar
TI  - Nimodipine activates TrkB neurotrophin receptors and induces neuroplastic and 
      neuroprotective signaling events in the mouse hippocampus and prefrontal cortex.
PG  - 189-96
LID - 10.1007/s10571-014-0110-5 [doi]
AB  - The L-type calcium channel blocker nimodipine improves clinical outcome produced 
      by delayed cortical ischemia or vasospasm associated with subarachnoid 
      hemorrhage. While vasoactive mechanisms are strongly implicated in these 
      therapeutic actions of nimodipine, we sought to test whether nimodipine might 
      also regulate neurotrophic and neuroplastic signaling events associated with TrkB 
      neurotrophin receptor activation. Adult male mice were acutely treated with 
      vehicle or nimodipine (10 mg/kg, s.c., 1.5 h) after which the phosphorylation 
      states of TrkB, cyclic-AMP response element binding protein (CREB), protein 
      kinase B (Akt), extracellular regulated kinase (ERK), mammalian target of 
      rapamycin (mTor) and p70S6 kinase (p70S6k) from prefrontal cortex and hippocampus 
      were assessed. Nimodipine increased the phosphorylation of the TrkB catalytic 
      domain and the phosphoslipase-Cgamma1 (PLCgamma1) domain, whereas phosphorylation of the 
      TrkB Shc binding site remained unaltered. Nimodipine-induced TrkB phosphorylation 
      was associated with increased phosphorylation levels of Akt and CREB in the 
      prefrontal cortex and the hippocampus whereas phosphorylation of ERK, mTor and 
      p70S6k remained unaltered. Nimodipine-induced TrkB signaling was not associated 
      with changes in BDNF mRNA or protein levels. These nimodipine-induced changes on 
      TrkB signaling mimic those produced by antidepressant drugs and thus propose 
      common mechanisms and long-term functional consequences for the effects of these 
      medications. This work provides a strong basis for investigating the role of 
      TrkB-associated signaling underlying the neuroprotective and neuroplastic effects 
      of nimodipine in translationally relevant animal models of brain trauma or 
      compromised synaptic plasticity.
FAU - Koskimaki, Janne
AU  - Koskimaki J
AD  - Neuroscience Center, University of Helsinki, P.O. Box 56 (Viikinkaari 4), 00014, 
      Helsinki, Finland.
FAU - Matsui, Nobuaki
AU  - Matsui N
FAU - Umemori, Juzoh
AU  - Umemori J
FAU - Rantamaki, Tomi
AU  - Rantamaki T
FAU - Castren, Eero
AU  - Castren E
LA  - eng
PT  - Journal Article
DEP - 20140910
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - 57WA9QZ5WH (Nimodipine)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Hippocampus/drug effects/*metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Neuronal Plasticity/*drug effects
MH  - Neuroprotective Agents/*metabolism
MH  - Nimodipine/administration & dosage/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Prefrontal Cortex/drug effects/*metabolism
MH  - Receptor, trkB/*metabolism
MH  - Signal Transduction/*drug effects
EDAT- 2014/09/11 06:00
MHDA- 2015/11/18 06:00
CRDT- 2014/09/11 06:00
PHST- 2014/07/29 00:00 [received]
PHST- 2014/09/01 00:00 [accepted]
PHST- 2014/09/11 06:00 [entrez]
PHST- 2014/09/11 06:00 [pubmed]
PHST- 2015/11/18 06:00 [medline]
AID - 10.1007/s10571-014-0110-5 [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2015 Mar;35(2):189-96. doi: 10.1007/s10571-014-0110-5. Epub 
      2014 Sep 10.