PMID- 30356704
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240402
IS  - 1662-5153 (Print)
IS  - 1662-5153 (Electronic)
IS  - 1662-5153 (Linking)
VI  - 12
DP  - 2018
TI  - Sex-Dependent Effects of Environmental Enrichment on Spatial Memory and 
      Brain-Derived Neurotrophic Factor (BDNF) Signaling in a Developmental "Two-Hit" 
      Mouse Model Combining BDNF Haploinsufficiency and Chronic Glucocorticoid 
      Stimulation.
PG  - 227
LID - 10.3389/fnbeh.2018.00227 [doi]
LID - 227
AB  - Neurodevelopmental disorders are thought to be caused by a combination of adverse 
      genetic and environmental insults. The "two-hit" hypothesis suggests that an 
      early first "hit" primes the developing brain to be vulnerable to a second "hit" 
      during adolescence which triggers behavioral dysfunction. We have previously 
      modeled this scenario in mice and found that the combined effect of a genetic 
      hapolinsuffuciency in the brain-derived neurotrophic factor (BDNF) gene (1st hit) 
      and chronic corticosterone (CORT) treatment during adolescence (2nd hit), caused 
      spatial memory impairments in adulthood. Environmental enrichment (EE) protocols 
      are designed to stimulate experience-dependent plasticity and have shown 
      therapeutic actions. This study investigated whether EE can reverse these spatial 
      memory impairments. Wild-type (WT) and BDNF heterozygous (HET) mice were treated 
      with corticosterone (CORT) in their drinking water (50 mg/L) from weeks 6 to 8 
      and exposed to EE from 7 to 9 weeks. Enriched housing included open top cages 
      with additional toys, tunnels, housing, and platforms. Y-maze novel preference 
      testing, to assess short-term spatial memory, was performed at 10 weeks of age. 
      At week 16 dorsal hippocampus tissue was obtained for Western blot analysis of 
      expression levels of BDNF, the BDNF receptor TrkB, and NMDA receptor subunits, 
      GluNR1, 2A and 2B. As in our previous studies, spatial memory was impaired in our 
      two-hit (BDNF HET + CORT) mice. Simultaneous EE prevented these impairments. 
      However, EE appeared to worsen spatial memory performance in WT mice, 
      particularly those exposed to CORT. While BDNF levels were lower in BDNF HET mice 
      as expected, there were no further effects of CORT or EE in males but a close to 
      significant female CORT x EE x genotype interaction which qualitatively 
      corresponded with Y-maze performance. However, EE caused both sex- and 
      genotype-specific effects on phosphorylated TrkB residues and GluNR expression 
      within the dorsal hippocampus, with GluNR2B levels in males changing in parallel 
      with spatial memory performance. In conclusion, beneficial effects of EE on 
      spatial memory emerge only following two developmental disruptions. The 
      mechanisms by which EE exerts its effects are likely via regulation of multiple 
      activity-dependent pathways, including TrkB and NMDA receptor signaling.
FAU - Grech, Adrienne M
AU  - Grech AM
AD  - Department of Psychiatry, School of Clinical Sciences, Monash Medical Centre, 
      Monash University, Clayton, VIC, Australia.
AD  - The Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Parkville, VIC, Australia.
FAU - Ratnayake, Udani
AU  - Ratnayake U
AD  - The Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Parkville, VIC, Australia.
FAU - Hannan, Anthony J
AU  - Hannan AJ
AD  - The Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Parkville, VIC, Australia.
FAU - van den Buuse, Maarten
AU  - van den Buuse M
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.
FAU - Hill, Rachel A
AU  - Hill RA
AD  - Department of Psychiatry, School of Clinical Sciences, Monash Medical Centre, 
      Monash University, Clayton, VIC, Australia.
AD  - The Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Parkville, VIC, Australia.
LA  - eng
PT  - Journal Article
DEP - 20181009
PL  - Switzerland
TA  - Front Behav Neurosci
JT  - Frontiers in behavioral neuroscience
JID - 101477952
PMC - PMC6189322
OTO - NOTNLM
OT  - brain-derived neurotrophic factor
OT  - corticosterone
OT  - environmental enrichment
OT  - hippocampus
OT  - neuroplasticity
OT  - spatial memory
OT  - stress
EDAT- 2018/10/26 06:00
MHDA- 2018/10/26 06:01
PMCR- 2018/01/01
CRDT- 2018/10/26 06:00
PHST- 2018/05/08 00:00 [received]
PHST- 2018/09/11 00:00 [accepted]
PHST- 2018/10/26 06:00 [entrez]
PHST- 2018/10/26 06:00 [pubmed]
PHST- 2018/10/26 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fnbeh.2018.00227 [doi]
PST - epublish
SO  - Front Behav Neurosci. 2018 Oct 9;12:227. doi: 10.3389/fnbeh.2018.00227. 
      eCollection 2018.