PMID- 30366002
OWN - NLM
STAT- MEDLINE
DCOM- 20190304
LR  - 20190304
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 144
DP  - 2019 Jan
TI  - Development of the MAM model of schizophrenia in mice: Sex similarities and 
      differences of hippocampal and prefrontal cortical function.
PG  - 193-207
LID - S0028-3908(18)30813-X [pii]
LID - 10.1016/j.neuropharm.2018.10.026 [doi]
AB  - Schizophrenia is a debilitating disorder with complex and unclarified etiological 
      factors. Sex differences have been observed in humans but animal models have only 
      focused on male subjects. In this study, we report the establishment of the 
      neurodevelopmental MAM model of schizophrenia in mice and compare the 
      schizotypic-like characteristics and cognitive functions in both sexes. Pregnant 
      mice were injected with methylazoxymethanol acetate (MAM) or saline on 
      gestational day (GD) 16 (MAM-16) or 17 (MAM-17). Female MAM-16, but not MAM-17 
      treated mice exhibited enhanced hyperlocomotion after acute MK-801 
      administration, compared to saline treated mice. Male MAM-16, but not MAM-17, 
      treated mice showed reduced pre-pulse inhibition of the acoustic startle reflex. 
      Both male and female MAM-16 and MAM-17 treated mice exhibited smaller hippocampal 
      (HPC) size and thinning of the prefrontal cortex (PFC), but only male MAM-16 
      treated mice showed decreased parvalbumin expression in HPC and PFC. Similarly, 
      both male and female MAM-16 treated mice displayed impaired contextual fear 
      memory and significantly reduced long-term potentiation (LTP) in the HPC CA1 
      synapses. However, male, but not female, MAM-16 treated mice exhibited deficits 
      in the delayed alternation task and LTP in layer II PFC synapses. Proteomic 
      analyses of PFC lysates further showed significant MAM- and sex-dependent 
      differences in protein expression regulation. Our results demonstrate that while 
      both male and female mice, prenatally exposed to MAM on GD16, display several 
      core schizophrenia-like deficits and impairments in the hippocampus, only male 
      MAM-treated mice have PFCdependent cognitive deficits.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Chalkiadaki, Kleanthi
AU  - Chalkiadaki K
AD  - Department of Biology, University of Crete, Voutes University Campus, Vassilika 
      Vouton, GR 70013, Heraklion, Greece.
FAU - Velli, Aggeliki
AU  - Velli A
AD  - Department of Biology, University of Crete, Voutes University Campus, Vassilika 
      Vouton, GR 70013, Heraklion, Greece.
FAU - Kyriazidis, Evangelos
AU  - Kyriazidis E
AD  - Department of Biology, University of Crete, Voutes University Campus, Vassilika 
      Vouton, GR 70013, Heraklion, Greece.
FAU - Stavroulaki, Vasiliki
AU  - Stavroulaki V
AD  - Department of Basic Sciences, Faculty of Medicine, University of Crete, 
      Heraklion, Greece.
FAU - Vouvoutsis, Vasilis
AU  - Vouvoutsis V
AD  - Department of Biology, University of Crete, Voutes University Campus, Vassilika 
      Vouton, GR 70013, Heraklion, Greece.
FAU - Chatzaki, Ekaterini
AU  - Chatzaki E
AD  - Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, 
      Alexandroupolis, Greece; Institute of Molecular Biology & Biotechnology, 
      Foundation for Research and Technology-Hellas, Heraklion, Greece.
FAU - Aivaliotis, Michalis
AU  - Aivaliotis M
AD  - Institute of Molecular Biology & Biotechnology, Foundation for Research and 
      Technology-Hellas, Heraklion, Greece; Laboratory of Biological Chemistry, School 
      of Medicine, Faculty of Life Sciences, Aristotle University of Thessaloniki, 
      Thessaloniki, Greece.
FAU - Sidiropoulou, Kyriaki
AU  - Sidiropoulou K
AD  - Department of Biology, University of Crete, Voutes University Campus, Vassilika 
      Vouton, GR 70013, Heraklion, Greece; Institute of Molecular Biology & 
      Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece. 
      Electronic address: sidirop@uoc.gr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181024
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Proteome)
RN  - 592-62-1 (Methylazoxymethanol Acetate)
SB  - IM
MH  - Animals
MH  - Auditory Perception/physiology
MH  - *Disease Models, Animal
MH  - Fear/physiology
MH  - Female
MH  - Hippocampus/pathology/*physiopathology
MH  - Long-Term Potentiation/physiology
MH  - Male
MH  - Memory/physiology
MH  - Methylazoxymethanol Acetate
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Prefrontal Cortex/pathology/*physiopathology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Prepulse Inhibition/physiology
MH  - Proteome
MH  - Reflex, Startle/physiology
MH  - Schizophrenia/pathology/*physiopathology
MH  - Schizophrenic Psychology
MH  - *Sex Characteristics
OTO - NOTNLM
OT  - Contextual fear memory
OT  - Long-term potentiation
OT  - Nissl staining
OT  - Parvalbumin
OT  - Proteomics
OT  - Working memory
EDAT- 2018/10/27 06:00
MHDA- 2019/03/05 06:00
CRDT- 2018/10/27 06:00
PHST- 2018/04/10 00:00 [received]
PHST- 2018/10/06 00:00 [revised]
PHST- 2018/10/19 00:00 [accepted]
PHST- 2018/10/27 06:00 [pubmed]
PHST- 2019/03/05 06:00 [medline]
PHST- 2018/10/27 06:00 [entrez]
AID - S0028-3908(18)30813-X [pii]
AID - 10.1016/j.neuropharm.2018.10.026 [doi]
PST - ppublish
SO  - Neuropharmacology. 2019 Jan;144:193-207. doi: 10.1016/j.neuropharm.2018.10.026. 
      Epub 2018 Oct 24.