PMID- 34769232
OWN - NLM
STAT- MEDLINE
DCOM- 20211216
LR  - 20211216
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 21
DP  - 2021 Oct 30
TI  - Cell Cycle Regulation of Hippocampal Progenitor Cells in Experimental Models of 
      Depression and after Treatment with Fluoxetine.
LID - 10.3390/ijms222111798 [doi]
LID - 11798
AB  - Changes in adult hippocampal cell proliferation and genesis have been largely 
      implicated in depression and antidepressant action, though surprisingly, the 
      underlying cell cycle mechanisms are largely undisclosed. Using both an in vivo 
      unpredictable chronic mild stress (uCMS) rat model of depression and in vitro rat 
      hippocampal-derived neurosphere culture approaches, we aimed to unravel the cell 
      cycle mechanisms regulating hippocampal cell proliferation and genesis in 
      depression and after antidepressant treatment. We show that the hippocampal 
      dentate gyrus (hDG) of uCMS animals have less proliferating cells and a decreased 
      proportion of cells in the G2/M phase, suggesting a G1 phase arrest; this is 
      accompanied by decreased levels of cyclin D1, E, and A expression. Chronic 
      fluoxetine treatment reversed the G1 phase arrest and promoted an up-regulation 
      of cyclin E. In vitro, dexamethasone (DEX) decreased cell proliferation, whereas 
      the administration of serotonin (5-HT) reversed it. DEX also induced a G1-phase 
      arrest and decreased cyclin D1 and D2 expression levels while increasing p27. 
      Additionally, 5-HT treatment could partly reverse the G1-phase arrest and 
      restored cyclin D1 expression. We suggest that the anti-proliferative actions of 
      chronic stress in the hDG result from a glucocorticoid-mediated G1-phase arrest 
      in the progenitor cells that is partly mediated by decreased cyclin D1 expression 
      which may be overcome by antidepressant treatment.
FAU - Patricio, Patricia
AU  - Patricio P
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.
AD  - ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimaraes, Portugal.
AD  - B'nML-Behavioral &Molecular Lab, 4715-057 Braga, Portugal.
FAU - Mateus-Pinheiro, Antonio
AU  - Mateus-Pinheiro A
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.
AD  - ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimaraes, Portugal.
AD  - B'nML-Behavioral &Molecular Lab, 4715-057 Braga, Portugal.
FAU - Machado-Santos, Ana Rita
AU  - Machado-Santos AR
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.
AD  - ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimaraes, Portugal.
FAU - Alves, Nuno Dinis
AU  - Alves ND
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.
AD  - ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimaraes, Portugal.
AD  - Department of Psychiatry, New York State Psychiatric Institute, Columbia 
      University, New York, NY 10032, USA.
FAU - Correia, Joana Sofia
AU  - Correia JS
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.
AD  - ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimaraes, Portugal.
FAU - Morais, Monica
AU  - Morais M
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.
AD  - ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimaraes, Portugal.
FAU - Bessa, Joao Miguel
AU  - Bessa JM
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.
AD  - ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimaraes, Portugal.
AD  - B'nML-Behavioral &Molecular Lab, 4715-057 Braga, Portugal.
FAU - Rodrigues, Ana Joao
AU  - Rodrigues AJ
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.
AD  - ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimaraes, Portugal.
FAU - Sousa, Nuno
AU  - Sousa N
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.
AD  - ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimaraes, Portugal.
FAU - Pinto, Luisa
AU  - Pinto L
AUID- ORCID: 0000-0002-7724-0446
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.
AD  - ICVS/3B's-PT Government Associate Laboratory, 4805-017 Braga/Guimaraes, Portugal.
AD  - B'nML-Behavioral &Molecular Lab, 4715-057 Braga, Portugal.
LA  - eng
GR  - IF/01079/2014; 2020.02855.CEECIND/Fundacao para a Ciencia e Tecnologia/
GR  - LP/Nature Research Award for Driving Global Impact - 2019 Brain Sciences/
GR  - UIDB/50026/2020; UIDP/50026/2020; NORTE-01-0145-FEDER-000013; 
      NORTE-01-0145-FEDER-000023/FEDER, through the Competitiveness 
      Internationalization Operational Program (POCI)/
GR  - PPBI-POCI-01-0145-FEDER-022122/PPBI - Portuguese Platform of Bioimaging/
PT  - Journal Article
DEP - 20211030
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Cyclins)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 333DO1RDJY (Serotonin)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Animals
MH  - Cyclins/*metabolism
MH  - *Depression/drug therapy/metabolism/pathology
MH  - Dexamethasone/pharmacology
MH  - Disease Models, Animal
MH  - Fluoxetine/*pharmacology
MH  - G1 Phase Cell Cycle Checkpoints/drug effects
MH  - Hippocampus/*metabolism/pathology
MH  - Male
MH  - Neural Stem Cells/*metabolism/pathology
MH  - Rats
MH  - Serotonin/pharmacology
PMC - PMC8584049
OTO - NOTNLM
OT  - antidepressants
OT  - cell cycle
OT  - depression
OT  - hippocampal cytogenesis
OT  - unpredictable chronic mild stress
COIS- The authors declare no conflict of interest.
EDAT- 2021/11/14 06:00
MHDA- 2021/12/17 06:00
PMCR- 2021/10/30
CRDT- 2021/11/13 01:05
PHST- 2021/09/28 00:00 [received]
PHST- 2021/10/26 00:00 [revised]
PHST- 2021/10/27 00:00 [accepted]
PHST- 2021/11/13 01:05 [entrez]
PHST- 2021/11/14 06:00 [pubmed]
PHST- 2021/12/17 06:00 [medline]
PHST- 2021/10/30 00:00 [pmc-release]
AID - ijms222111798 [pii]
AID - ijms-22-11798 [pii]
AID - 10.3390/ijms222111798 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Oct 30;22(21):11798. doi: 10.3390/ijms222111798.