PMID- 28925523
OWN - NLM
STAT- MEDLINE
DCOM- 20191114
LR  - 20191114
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Linking)
VI  - 48
IP  - 8
DP  - 2018 Oct
TI  - Brain-derived neurotrophic factor haploinsufficiency impairs high-frequency 
      cortical oscillations in mice.
PG  - 2816-2825
LID - 10.1111/ejn.13722 [doi]
AB  - Schizophrenia is a complex psychiatric disorder with a heterogeneous aetiology 
      involving genetic and environmental factors. Deficiencies in both brain-derived 
      neurotrophic factor (BDNF) and NMDA receptor function have been implicated in the 
      disorder and may play causal and synergistic roles. Perturbations in the 
      regulation of electrophysiological signals, including high-frequency (gamma: 30-80 Hz 
      and beta: 20-30 Hz) neuronal oscillations, are also associated with the disorder. 
      This study investigated the influence of BDNF deficiency and NMDA receptor 
      hypofunction on electrophysiological responses to brief acoustic stimuli. Adult 
      BDNF heterozygote (BDNF(+/-) ) and wild-type littermate C57Bl/6J mice were 
      surgically implanted with EEG recording electrodes. All mice underwent EEG 
      recording sessions to measure ongoing and auditory-evoked electrophysiological 
      responses following treatment with MK-801 (0.3 mg/kg ip) or vehicle. Western 
      blotting on post-mortem cortical tissue assessed parvalbumin and GAD67 expression 
      - markers of interneurons which are involved in the generation of gamma 
      oscillations. Compared with wild-type controls, BDNF(+/-) mice exhibited markedly 
      dampened electrophysiological responses to auditory stimuli, including reductions 
      in the amplitude of multiple components of the event-related potential and 
      auditory-evoked oscillations, as well as reduced ongoing cortical gamma 
      oscillations. MK-801 elevated ongoing gamma power but suppressed evoked gamma 
      power, and this was observed equally across genotypes. BDNF(+/-) mice also 
      displayed reductions in parvalbumin, but not GAD67 expression. We conclude that 
      reduced BDNF expression leads to impairments in the generation of high-frequency 
      neural oscillations, but this is not synergistic with NMDA receptor hypofunction. 
      Reduced parvalbumin expression associated with BDNF haploinsufficiency may 
      provide a molecular explanation for these electrophysiological deficits.
CI  - (c) 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
FAU - Jones, Nigel C
AU  - Jones NC
AUID- ORCID: 0000-0002-1080-8439
AD  - Department of Medicine, Melbourne Brain Centre, Royal Melbourne Hospital, 
      University of Melbourne, Parkville, Vic., 3052, Australia.
AD  - Department of Neuroscience, Central Clinical School, Monash University, 
      Melbourne, Vic., Australia.
AD  - Department of Neurology, The Alfred Hospital, Melbourne, Vic., Australia.
FAU - Hudson, Matthew
AU  - Hudson M
AD  - Department of Medicine, Melbourne Brain Centre, Royal Melbourne Hospital, 
      University of Melbourne, Parkville, Vic., 3052, Australia.
FAU - Foreman, Joshua
AU  - Foreman J
AD  - Department of Medicine, Melbourne Brain Centre, Royal Melbourne Hospital, 
      University of Melbourne, Parkville, Vic., 3052, Australia.
FAU - Rind, Gil
AU  - Rind G
AD  - Department of Medicine, Melbourne Brain Centre, Royal Melbourne Hospital, 
      University of Melbourne, Parkville, Vic., 3052, Australia.
FAU - Hill, Rachel
AU  - Hill R
AD  - Department of Psychiatry, Monash University, Melbourne, Vic., Australia.
AD  - Melbourne Brain Centre, Florey Institutes of Neuroscience and Mental Health, 
      University of Melbourne, Parkville, Vic., Australia.
FAU - Manning, Elizabeth E
AU  - Manning EE
AD  - Melbourne Brain Centre, Florey Institutes of Neuroscience and Mental Health, 
      University of Melbourne, Parkville, Vic., Australia.
FAU - van den Buuse, Maarten
AU  - van den Buuse M
AD  - Melbourne Brain Centre, Florey Institutes of Neuroscience and Mental Health, 
      University of Melbourne, Parkville, Vic., Australia.
AD  - School of Psychology and Public Health, La Trobe University, Melbourne, Vic., 
      Australia.
AD  - Department of Pharmacology, University of Melbourne, Melbourne, Vic., Australia.
AD  - The College of Public Health, Medical and Veterinary Sciences, James Cook 
      University, Townsville, QLD, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171106
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Bdnf protein, mouse)
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Brain Waves/*physiology
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics
MH  - Haploinsufficiency/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Prefrontal Cortex/*metabolism
OTO - NOTNLM
OT  - NMDA receptors
OT  - brain-derived neurotrophic factor
OT  - electrophysiology
OT  - event-related potential
OT  - gamma oscillations
OT  - parvalbumin
EDAT- 2017/09/20 06:00
MHDA- 2019/11/15 06:00
CRDT- 2017/09/20 06:00
PHST- 2017/06/26 00:00 [received]
PHST- 2017/08/30 00:00 [revised]
PHST- 2017/09/13 00:00 [accepted]
PHST- 2017/09/20 06:00 [pubmed]
PHST- 2019/11/15 06:00 [medline]
PHST- 2017/09/20 06:00 [entrez]
AID - 10.1111/ejn.13722 [doi]
PST - ppublish
SO  - Eur J Neurosci. 2018 Oct;48(8):2816-2825. doi: 10.1111/ejn.13722. Epub 2017 Nov 
      6.