PMID- 23704876
OWN - NLM
STAT- MEDLINE
DCOM- 20131230
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 5
DP  - 2013
TI  - Enriched environment prevents hypobaric hypoxia induced memory impairment and 
      neurodegeneration: role of BDNF/PI3K/GSK3beta pathway coupled with CREB activation.
PG  - e62235
LID - 10.1371/journal.pone.0062235 [doi]
LID - e62235
AB  - Adverse environmental conditions such as hypobaric hypoxia (HH) cause memory 
      impairment by affecting cellular machinery leading to neurodegeneration. 
      Providing enriched environment (EE) is found to be beneficial for curing several 
      neurodegenerative disorders. The protective role of EE in preventing HH induced 
      neuronal death has been reported previously but the involved mechanism is still 
      not clearly understood. The present study is an attempt to verify the impact of 
      EE on spatial memory during HH and also to explore the possible role of 
      neurotrophin in EE mediated neuroprotection. Signaling mechanism involved in 
      neuroprotection was also explored. Male Sprague Dawley rats were simulated to HH 
      condition in an Animal Decompression Chamber at an altitude of 25000 feet in 
      standard and enriched cages for 7 days. Spatial memory was assessed through 
      Morris Water Maze. Role of different neurotrophins was explored by gene silencing 
      and inhibitors for their respective receptors. Further, using different blockers 
      signaling pathway was also explored. Finding of the present study suggested that 
      EE prevents HH mediated memory impairment and neurodegeneration. Also 
      brain-derived neurotrophic factor (BDNF) plays a major role in EE mediated 
      neuroprotection and it effectively prevented neurodegeneration by activating 
      PI3K/AKT pathway resulting in GSK3beta inactivation which further inhibits 
      apoptosis. Moreover GSK3beta phosphorylation and hence its inactivation upregulates 
      CREB phosphorylation which may also accounts for activation of survival machinery 
      in cells and provides neuroprotection. From these observations it can be 
      postulated that EE has a therapeutic potential in amelioration of HH induced 
      memory impairment and neurodegeneration. Hence it may be used as a non invasive 
      and non pharmacological intervention against various neurological disorders.
FAU - Jain, Vishal
AU  - Jain V
AD  - Department of Neurobiology, Defence Institute of Physiology and Allied Sciences 
      (DIPAS), Delhi, India.
FAU - Baitharu, Iswar
AU  - Baitharu I
FAU - Prasad, Dipti
AU  - Prasad D
FAU - Ilavazhagan, Govindasamy
AU  - Ilavazhagan G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130521
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neuroprotective Agents)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Animals
MH  - Behavior, Animal
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Death
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - Environment
MH  - Enzyme Activation
MH  - Gene Knockdown Techniques
MH  - Glycogen Synthase Kinase 3/antagonists & inhibitors/*metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Hypoxia/*complications/enzymology/pathology
MH  - Male
MH  - Maze Learning
MH  - Memory Disorders/enzymology/*etiology/pathology
MH  - Models, Biological
MH  - Nerve Degeneration/enzymology/*etiology/pathology
MH  - Nerve Growth Factors/metabolism
MH  - Neuroprotective Agents/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/metabolism
MH  - Signal Transduction
PMC - PMC3660501
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/05/25 06:00
MHDA- 2014/01/01 06:00
PMCR- 2013/05/21
CRDT- 2013/05/25 06:00
PHST- 2013/01/09 00:00 [received]
PHST- 2013/03/18 00:00 [accepted]
PHST- 2013/05/25 06:00 [entrez]
PHST- 2013/05/25 06:00 [pubmed]
PHST- 2014/01/01 06:00 [medline]
PHST- 2013/05/21 00:00 [pmc-release]
AID - PONE-D-13-01411 [pii]
AID - 10.1371/journal.pone.0062235 [doi]
PST - epublish
SO  - PLoS One. 2013 May 21;8(5):e62235. doi: 10.1371/journal.pone.0062235. Print 2013.