PMID- 23219906
OWN - NLM
STAT- MEDLINE
DCOM- 20130725
LR  - 20130129
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 231
DP  - 2013 Feb 12
TI  - Chronic treadmill running protects hippocampal neurons from hypobaric 
      hypoxia-induced apoptosis in rats.
PG  - 216-24
LID - S0306-4522(12)01162-1 [pii]
LID - 10.1016/j.neuroscience.2012.11.051 [doi]
AB  - This study was designed to examine the effects of chronic running exercise (Ex) 
      on the hypobaric hypoxia-induced neuronal injury in the hippocampus. Male Wistar 
      rats (9 weeks old) were caged in a hypoxic altitude chamber simulating the 
      condition of 9,000 m high (0.303 atm) for 7h and the brains were examined at 0, 
      4, and 24h after treatment. Hypoxia challenge increased the levels of caspase 3 
      (mean +/- SEM, % of baseline control, 121.9 +/- 11.8, 152.3 +/- 15.3, 141.6 +/- 7.0 for 
      0, 4 and 24h, respectively, n=5) and induced apoptosis (cell number, 205.7 +/- 8.8, 
      342.3 +/- 33.4, 403.0 +/- 12.2 for 0, 4 and 24h vs. 7.7 +/- 1.4 baseline control, n=3) 
      in the hippocampal CA1 pyramidal neurons. The expression levels (% of control for 
      0, 4 and 24h, respectively, n=5) of hypoxia inducible factor-1alpha (HIF-1alpha; 150.5 +/- 
      8.1, 176.7 +/- 11.1, 136.2 +/- 13.3), neuronal nitric oxide synthase (nNOS; 163.4 +/- 
      9.6, 194.5 +/- 13.6, 163.7 +/- 10.9) and inducible nitric oxide synthase (iNOS; 139.4 
      +/- 9.5, 169.2 +/- 13.3, 134.3 +/- 13.0) and the degrees of microglia (cell number, 
      255.3 +/- 48.2, 349.0 +/- 57.3, 433.7 +/- 42.4 vs. 57.7 +/- 13.0 baseline control, n=3) 
      and astrocyte (150.0 +/- 9.7, 199.3 +/- 10.8, 154.2 +/- 4.7) activation were increased 
      by the hypoxia treatment, indicating that the brain was under hypoxic, oxidative 
      and inflammatory stresses. Furthermore, the protein levels of hippocampal 
      brain-derived neurotrophic factor (BDNF; 76.0 +/- 2.5, 76.1 +/- 7.1, 69.3 +/- 1.7 for 
      0, 4 and 24h, respectively, mean % of control +/- SEM, n=5) were reduced by the 
      hypoxia treatment. Four weeks of treadmill Ex before hypoxia treatment 
      significantly reduced the hypoxia-induced apoptosis (p<0.001, n=3) in the 
      hippocampal CA1 neurons. Ex decreased the hypoxia-induced elevations of HIF-1alpha 
      (p<0.001, n=5), nNOS (p<0.001, n=5) and iNOS (p<0.001, n=5) levels and activation 
      of microglia (p=0.005, n=3) and astrocyte (p<0.001, n=5) status; whereas the 
      hypoxia-reduced BDNF protein levels (p=0.013, n=5) were restored. Taken together, 
      our results show that chronic Ex protects hippocampal CA1 neurons against 
      hypobaric hypoxia insult. Ex-enhanced bioenergetic adaptation and anti-oxidative 
      capacity may prevent neurons from hypoxia-induced apoptosis. Furthermore, 
      activation of the BDNF signaling pathway may be involved in the Ex-induced 
      protection.
CI  - Copyright (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Lin, C
AU  - Lin C
AD  - Department of Physiology, China Medical University, Taichung, Taiwan. 
      clin33@mail.cmu.edu.tw
FAU - Wu, C-J
AU  - Wu CJ
FAU - Wei, I-H
AU  - Wei IH
FAU - Tsai, M-H
AU  - Tsai MH
FAU - Chang, N-W
AU  - Chang NW
FAU - Yang, T-T
AU  - Yang TT
FAU - Kuo, Y-M
AU  - Kuo YM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121207
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Astrocytes/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Hippocampus/*metabolism
MH  - Hypoxia, Brain/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Inflammation
MH  - Male
MH  - Microglia/metabolism
MH  - Neurons/*pathology
MH  - Nitric Oxide Synthase Type I/metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Physical Conditioning, Animal/*physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Running
EDAT- 2012/12/12 06:00
MHDA- 2013/07/26 06:00
CRDT- 2012/12/11 06:00
PHST- 2012/10/01 00:00 [received]
PHST- 2012/11/20 00:00 [revised]
PHST- 2012/11/28 00:00 [accepted]
PHST- 2012/12/11 06:00 [entrez]
PHST- 2012/12/12 06:00 [pubmed]
PHST- 2013/07/26 06:00 [medline]
AID - S0306-4522(12)01162-1 [pii]
AID - 10.1016/j.neuroscience.2012.11.051 [doi]
PST - ppublish
SO  - Neuroscience. 2013 Feb 12;231:216-24. doi: 10.1016/j.neuroscience.2012.11.051. 
      Epub 2012 Dec 7.