PMID- 32399718
OWN - NLM
STAT- MEDLINE
DCOM- 20210614
LR  - 20221207
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 38
IP  - 2
DP  - 2020 Aug
TI  - Protective Effects of Agmatine Against Corticosterone-Induced Impairment on 
      Hippocampal mTOR Signaling and Cell Death.
PG  - 319-329
LID - 10.1007/s12640-020-00212-1 [doi]
AB  - Chronic treatment with agmatine, similarly to fluoxetine, may cause 
      antidepressant-like effects mediated, at least in part, by the modulation of 
      hippocampal plasticity. However, the ability of chronic treatment with agmatine 
      to cause antidepressant-like effects associated with the modulation of mammalian 
      target of rapamycin (mTOR) signaling pathway and protection against neuronal 
      death remains to be established. In this study, we investigated the effects of 
      agmatine (0.1 mg/kg, p.o.) and the conventional antidepressant fluoxetine 
      (10 mg/kg, p.o.) treatment on the levels of phosphorylated mTOR (p-mTOR), 
      neuronal death, and overall volume in the hippocampal dentate gyrus (DG) of mice 
      exposed to chronic corticosterone (20 mg/kg, p.o.) treatment for 21 days, a model 
      of stress and depressive-like behavior. Chronic corticosterone treatment 
      increased cell death in the sub-granular zone (SGZ) of the DG, as assessed by 
      Fluoro-Jade B labeling. Agmatine, similarly to fluoxetine, was capable of 
      reversing this alteration in the entire DG, an effect more evident in the ventral 
      portion of the hippocampus. Additionally, reduced phosphorylation of mTOR 
      (Ser(2448)), a pro-survival protein that is active when phosphorylated at 
      Ser(2448), was observed in the whole hippocampal DG in corticosterone-treated 
      mice, an effect not observed in agmatine or fluoxetine-treated mice. Chronic 
      exposure to corticosterone caused a significant reduction in overall hippocampal 
      volume, although no alterations were observed between the groups with regards 
      to DG volume. Altogether, the results indicate that agmatine, similar to 
      fluoxetine, was able to counteract corticosterone-induced impairment on mTOR 
      signaling and cell death in hippocampal DG.
FAU - Olescowicz, Gislaine
AU  - Olescowicz G
AUID- ORCID: 0000-0002-7462-3150
AD  - Department of Pharmacology, Center of Biological Sciences, Federal University of 
      Santa Catarina, Florianopolis, SC, 88040-900, Brazil.
FAU - Sampaio, Tuane B
AU  - Sampaio TB
AUID- ORCID: 0000-0002-6149-9226
AD  - Department of Pharmacology, Center of Biological Sciences, Federal University of 
      Santa Catarina, Florianopolis, SC, 88040-900, Brazil.
FAU - de Paula Nascimento-Castro, Cristine
AU  - de Paula Nascimento-Castro C
AUID- ORCID: 0000-0003-1435-8006
AD  - Department of Morphological Sciences, Center of Biological Sciences, Federal 
      University of Santa Catarina, Florianopolis, SC, 88040-900, Brazil.
FAU - Brocardo, Patricia S
AU  - Brocardo PS
AUID- ORCID: 0000-0002-1680-5909
AD  - Department of Morphological Sciences, Center of Biological Sciences, Federal 
      University of Santa Catarina, Florianopolis, SC, 88040-900, Brazil.
FAU - Gil-Mohapel, Joana
AU  - Gil-Mohapel J
AUID- ORCID: 0000-0003-4982-1662
AD  - Division of Medical Sciences, University of Victoria, and Island Medical Program, 
      Faculty of Medicine, University of British Columbia, Victoria, British Columbia, 
      Canada.
FAU - Rodrigues, Ana Lucia S
AU  - Rodrigues ALS
AUID- ORCID: 0000-0001-6285-8780
AD  - Department of Biochemistry, Center of Biological Sciences, Federal University of 
      Santa Catarina, Florianopolis, SC, 88040-900, Brazil. alsrodri@gmail.com.
LA  - eng
GR  - 310113/2017-2/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/
GR  - 403120/2012-8/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/
GR  - 449436/2014-4/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/
PT  - Journal Article
DEP - 20200512
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 70J407ZL5Q (Agmatine)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Agmatine/*pharmacology
MH  - Animals
MH  - Anti-Inflammatory Agents/*toxicity
MH  - Cell Death/drug effects
MH  - Corticosterone/*toxicity
MH  - Dentate Gyrus/cytology/drug effects
MH  - Fluoxetine/pharmacology
MH  - Hippocampus/*drug effects/metabolism
MH  - Mice
MH  - Neurons/*drug effects
MH  - Neuroprotective Agents/*pharmacology
MH  - Selective Serotonin Reuptake Inhibitors/pharmacology
MH  - TOR Serine-Threonine Kinases/*drug effects/metabolism
OTO - NOTNLM
OT  - Agmatine
OT  - Depression
OT  - Hippocampus
OT  - Neuronal damage
OT  - mTOR
EDAT- 2020/05/14 06:00
MHDA- 2021/06/16 06:00
CRDT- 2020/05/14 06:00
PHST- 2019/09/07 00:00 [received]
PHST- 2020/04/22 00:00 [accepted]
PHST- 2020/04/06 00:00 [revised]
PHST- 2020/05/14 06:00 [pubmed]
PHST- 2021/06/16 06:00 [medline]
PHST- 2020/05/14 06:00 [entrez]
AID - 10.1007/s12640-020-00212-1 [pii]
AID - 10.1007/s12640-020-00212-1 [doi]
PST - ppublish
SO  - Neurotox Res. 2020 Aug;38(2):319-329. doi: 10.1007/s12640-020-00212-1. Epub 2020 
      May 12.