PMID- 28218311
OWN - NLM
STAT- MEDLINE
DCOM- 20181029
LR  - 20190917
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
DP  - 2017 Feb 20
TI  - S 38093, a histamine H(3) antagonist/inverse agonist, promotes hippocampal 
      neurogenesis and improves context discrimination task in aged mice.
PG  - 42946
LID - 10.1038/srep42946 [doi]
LID - 42946
AB  - Strategies designed to increase adult hippocampal neurogenesis (AHN) may have 
      therapeutic potential for reversing memory impairments. H(3) receptor 
      antagonists/inverse agonists also may be useful for treating cognitive deficits. 
      However, it remains unclear whether these ligands have effects on AHN. The 
      present study aimed to investigate the effects of a 28-day treatment with S 
      38093, a novel brain-penetrant antagonist/inverse agonist of H(3) receptors, on 
      AHN (proliferation, maturation and survival) in 3-month-old and in aged 
      16-month-old mice. In addition, the effects of S 38093 treatment on 7-month-old 
      APPSWE Tg2576 transgenic mice, a model of Alzheimer's disease, were also 
      assessed. In all tested models, chronic treatment with S 38093 stimulated all 
      steps of AHN. In aged animals, S 38093 induced a reversal of age-dependent 
      effects on hippocampal brain-derived neurotrophic factor (BDNF) BDNF-IX, BDNF-IV 
      and BDNF-I transcripts and increased vascular endothelial growth factor (VEGF) 
      expression. Finally, the effects of chronic administration of S 38093 were 
      assessed on a neurogenesis-dependent "context discrimination (CS) test" in aged 
      mice. While ageing altered mouse CS, chronic S 38093 treatment significantly 
      improved CS. Taken together, these results provide evidence that chronic S 38093 
      treatment increases adult hippocampal neurogenesis and may provide an innovative 
      strategy to improve age-associated cognitive deficits.
FAU - Guilloux, Jean-Philippe
AU  - Guilloux JP
AD  - CESP/UMR-S1178, Univ. Paris-Sud, Fac. Pharmacie, INSERM, Universite Paris-Saclay, 
      Chatenay-Malabry, France.
FAU - Samuels, Benjamin A
AU  - Samuels BA
AD  - Behavioral and Systems Neuroscience Area, Department of Psychology, Rutgers The 
      State University of New Jersey, Piscataway, NJ, USA.
FAU - Mendez-David, Indira
AU  - Mendez-David I
AD  - CESP/UMR-S1178, Univ. Paris-Sud, Fac. Pharmacie, INSERM, Universite Paris-Saclay, 
      Chatenay-Malabry, France.
FAU - Hu, Alice
AU  - Hu A
AD  - Departments of Neuroscience and Psychiatry, Columbia University, New York, USA.
FAU - Levinstein, Marjorie
AU  - Levinstein M
AD  - Departments of Neuroscience and Psychiatry, Columbia University, New York, USA.
FAU - Faye, Charlene
AU  - Faye C
AD  - CESP/UMR-S1178, Univ. Paris-Sud, Fac. Pharmacie, INSERM, Universite Paris-Saclay, 
      Chatenay-Malabry, France.
FAU - Mekiri, Maryam
AU  - Mekiri M
AD  - CESP/UMR-S1178, Univ. Paris-Sud, Fac. Pharmacie, INSERM, Universite Paris-Saclay, 
      Chatenay-Malabry, France.
FAU - Mocaer, Elisabeth
AU  - Mocaer E
AD  - Pole d'Innovation Therapeutique Neuropsychiatrie Servier, Suresnes, France.
FAU - Gardier, Alain M
AU  - Gardier AM
AD  - CESP/UMR-S1178, Univ. Paris-Sud, Fac. Pharmacie, INSERM, Universite Paris-Saclay, 
      Chatenay-Malabry, France.
FAU - Hen, Rene
AU  - Hen R
AD  - Departments of Neuroscience and Psychiatry, Columbia University, New York, USA.
AD  - Department of Integrative Neuroscience, New York State Psychiatric Institute, New 
      York, USA.
FAU - Sors, Aurore
AU  - Sors A
AD  - Pole d'Innovation Therapeutique Neuropsychiatrie Servier, Suresnes, France.
FAU - David, Denis J
AU  - David DJ
AD  - CESP/UMR-S1178, Univ. Paris-Sud, Fac. Pharmacie, INSERM, Universite Paris-Saclay, 
      Chatenay-Malabry, France.
LA  - eng
GR  - R01 AG043688/AG/NIA NIH HHS/United States
GR  - R01 MH112861/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20170220
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Azabicyclo Compounds)
RN  - 0 (Benzamides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Histamine H3 Antagonists)
RN  - 0 (S 38093)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - *Aging
MH  - Alzheimer Disease/pathology
MH  - Animals
MH  - Azabicyclo Compounds/*pharmacology
MH  - Behavior, Animal/*drug effects
MH  - Benzamides/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Cell Proliferation/drug effects
MH  - Dentate Gyrus/metabolism
MH  - Disease Models, Animal
MH  - Drug Inverse Agonism
MH  - Hippocampus/cytology/drug effects/metabolism
MH  - Histamine H3 Antagonists/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neurogenesis/*drug effects
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
PMC - PMC5317168
COIS- Pr Denis J. David serves as a consultant for Lundbeck, Roche, and Servier. Pr 
      Rene Hen receives compensation as a consultant for Roche, Lundbeck and Servier in 
      relation to the generation of novel antidepressants. All other authors report no 
      biomedical financial interests or potential conflicts of interest.
EDAT- 2017/02/22 06:00
MHDA- 2018/10/30 06:00
PMCR- 2017/02/20
CRDT- 2017/02/21 06:00
PHST- 2016/10/10 00:00 [received]
PHST- 2017/01/17 00:00 [accepted]
PHST- 2017/02/21 06:00 [entrez]
PHST- 2017/02/22 06:00 [pubmed]
PHST- 2018/10/30 06:00 [medline]
PHST- 2017/02/20 00:00 [pmc-release]
AID - srep42946 [pii]
AID - 10.1038/srep42946 [doi]
PST - epublish
SO  - Sci Rep. 2017 Feb 20;7:42946. doi: 10.1038/srep42946.