PMID- 25598009
OWN - NLM
STAT- MEDLINE
DCOM- 20160524
LR  - 20220321
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 172
IP  - 10
DP  - 2015 May
TI  - In vitro and in vivo regulation of synaptogenesis by the novel antidepressant 
      spadin.
PG  - 2604-17
LID - 10.1111/bph.13083 [doi]
AB  - BACKGROUND AND PURPOSE: We have described a novel antidepressant peptide, spadin, 
      that acts by blocking the TWIK-related-potassium channel, type 1 (TREK-1). Here, 
      we examined possible mechanisms of action of spadin at both molecular and 
      cellular levels. EXPERIMENTAL APPROACHES: Effects of spadin were measured in 
      primary cultures of neurons or tissues from mice injected i.v. with spadin. 
      Western blots, qPCR, histochemical and electrophysiological techniques were used. 
      KEY RESULTS: In vitro, spadin increased neuronal membrane potential and activated 
      both the MAPK and PI3K signalling pathways, in a time- and 
      concentration-dependent manner. The latter pathway was involved in the protective 
      effect of spadin against staurosporine-induced apoptosis. Also, spadin enhanced 
      both mRNA expression and protein of two markers of synaptogenesis, the 
      post-synaptic density protein of 95 kDalton (PSD-95) and synapsin. We confirmed 
      these effects on synaptogenesis by the observation that spadin treatment 
      significantly increased the proportion of mature spines in cortical neurons. 
      Finally, in vivo injections of spadin led to a rapid increase in both mRNA 
      expression and protein level of brain-derived neurotrophic factor (BDNF) in the 
      hippocampus, confirming the antidepressant action of the peptide. We argue for a 
      new role of spadin in synaptogenesis as both PSD-95 and synapsin mRNA expression 
      and protein levels were further enhanced in the hippocampus, following treatment 
      in vivo with the peptide. CONCLUSIONS AND IMPLICATIONS: These findings provide 
      new mechanisms of action for the rapidly acting antidepressant peptide spadin by 
      stimulating expression of BDNF and synaptic proteins, both in vitro and in vivo.
CI  - (c) 2015 The British Pharmacological Society.
FAU - Devader, C
AU  - Devader C
AD  - CNRS, Institut de Pharmacologie Moleculaire et Cellulaire, UMR 7275, Universite 
      de Nice-Sophia Antipolis, Valbonne, France.
FAU - Khayachi, A
AU  - Khayachi A
FAU - Veyssiere, J
AU  - Veyssiere J
FAU - Moha Ou Maati, H
AU  - Moha Ou Maati H
FAU - Roulot, M
AU  - Roulot M
FAU - Moreno, S
AU  - Moreno S
FAU - Borsotto, M
AU  - Borsotto M
FAU - Martin, S
AU  - Martin S
FAU - Heurteaux, C
AU  - Heurteaux C
FAU - Mazella, J
AU  - Mazella J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150324
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Peptides)
RN  - 0 (Synapsins)
RN  - 0 (spadin peptide)
RN  - EC 2.7.4.8 (Guanylate Kinases)
RN  - H88EPA0A3N (Staurosporine)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Disks Large Homolog 4 Protein
MH  - Dose-Response Relationship, Drug
MH  - Guanylate Kinases/metabolism
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - Membrane Potentials/drug effects
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Neurons/cytology/*drug effects/physiology
MH  - Peptides/*pharmacology
MH  - Primary Cell Culture
MH  - Signal Transduction/drug effects
MH  - Staurosporine/toxicity
MH  - Synapses/*drug effects
MH  - Synapsins/metabolism
PMC - PMC4409910
EDAT- 2015/01/20 06:00
MHDA- 2016/05/25 06:00
PMCR- 2016/05/01
CRDT- 2015/01/20 06:00
PHST- 2014/06/24 00:00 [received]
PHST- 2014/12/10 00:00 [revised]
PHST- 2015/01/08 00:00 [accepted]
PHST- 2015/01/20 06:00 [entrez]
PHST- 2015/01/20 06:00 [pubmed]
PHST- 2016/05/25 06:00 [medline]
PHST- 2016/05/01 00:00 [pmc-release]
AID - 10.1111/bph.13083 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2015 May;172(10):2604-17. doi: 10.1111/bph.13083. Epub 2015 Mar 
      24.