PMID- 25603414
OWN - NLM
STAT- MEDLINE
DCOM- 20150909
LR  - 20181113
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 5
IP  - 1
DP  - 2015 Jan 20
TI  - Analyzing the influence of BDNF heterozygosity on spatial memory response to 
      17beta-estradiol.
PG  - e498
LID - 10.1038/tp.2014.143 [doi]
AB  - The recent use of estrogen-based therapies as adjunctive treatments for the 
      cognitive impairments of schizophrenia has produced promising results; however 
      the mechanism behind estrogen-based cognitive enhancement is relatively unknown. 
      Brain-derived neurotrophic factor (BDNF) regulates learning and memory and its 
      expression is highly responsive to estradiol. We recently found that estradiol 
      modulates the expression of hippocampal parvalbumin-positive GABAergic 
      interneurons, known to regulate neuronal synchrony and cognitive function. What 
      is unknown is whether disruptions to the aforementioned estradiol-parvalbumin 
      pathway alter learning and memory, and whether BDNF may mediate these events. 
      Wild-type (WT) and BDNF heterozygous (+/-) mice were ovariectomized (OVX) at 5 
      weeks of age and simultaneously received empty, estradiol- or progesterone-filled 
      implants for 7 weeks. At young adulthood, mice were tested for spatial and 
      recognition memory in the Y-maze and novel-object recognition test, respectively. 
      Hippocampal protein expression of BDNF and GABAergic interneuron markers, 
      including parvalbumin, were assessed. WT OVX mice show impaired performance on 
      Y-maze and novel-object recognition test. Estradiol replacement in OVX mice 
      prevented the Y-maze impairment, a Behavioral abnormality of dorsal hippocampal 
      origin. BDNF and parvalbumin protein expression in the dorsal hippocampus and 
      parvalbumin-positive cell number in the dorsal CA1 were significantly reduced by 
      OVX in WT mice, while E2 replacement prevented these deficits. In contrast, 
      BDNF(+/-) mice showed either no response or an opposite response to hormone 
      manipulation in both behavioral and molecular indices. Our data suggest that BDNF 
      status is an important biomarker for predicting responsiveness to estrogenic 
      compounds which have emerged as promising adjunctive therapeutics for 
      schizophrenia patients.
FAU - Wu, Y W C
AU  - Wu YW
AD  - 1] Behavioural Neuroscience Laboratory, Florey Institute of Neuroscience and 
      Mental Health, University of Melbourne, Parkville, VIC, Australia [2] Department 
      of Pharmacology and Therapeutics, University of Melbourne, Parkville, VIC, 
      Australia.
FAU - Du, X
AU  - Du X
AD  - Behavioural Neuroscience Laboratory, Florey Institute of Neuroscience and Mental 
      Health, University of Melbourne, Parkville, VIC, Australia.
FAU - van den Buuse, M
AU  - van den Buuse M
AD  - 1] Behavioural Neuroscience Laboratory, Florey Institute of Neuroscience and 
      Mental Health, University of Melbourne, Parkville, VIC, Australia [2] Department 
      of Pharmacology and Therapeutics, University of Melbourne, Parkville, VIC, 
      Australia [3] School of Psychological Science, La Trobe University, Melbourne, 
      VIC, Australia.
FAU - Hill, R A
AU  - Hill RA
AD  - Behavioural Neuroscience Laboratory, Florey Institute of Neuroscience and Mental 
      Health, University of Melbourne, Parkville, VIC, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150120
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Estrogens)
RN  - 0 (Parvalbumins)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects/physiology
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - CA1 Region, Hippocampal/*drug effects/metabolism
MH  - Estradiol/*pharmacology
MH  - Estrogens/*pharmacology
MH  - Female
MH  - Gene-Environment Interaction
MH  - Heterozygote
MH  - Hippocampus/drug effects/metabolism
MH  - Maze Learning/*drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Ovariectomy
MH  - Parvalbumins/drug effects/metabolism
MH  - Spatial Memory/*drug effects/physiology
PMC - PMC4312832
EDAT- 2015/01/21 06:00
MHDA- 2015/09/10 06:00
PMCR- 2015/01/01
CRDT- 2015/01/21 06:00
PHST- 2014/11/16 00:00 [received]
PHST- 2014/12/02 00:00 [accepted]
PHST- 2015/01/21 06:00 [entrez]
PHST- 2015/01/21 06:00 [pubmed]
PHST- 2015/09/10 06:00 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - tp2014143 [pii]
AID - 10.1038/tp.2014.143 [doi]
PST - epublish
SO  - Transl Psychiatry. 2015 Jan 20;5(1):e498. doi: 10.1038/tp.2014.143.