PMID- 31000957
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 0972-7531 (Print)
IS  - 0976-3260 (Electronic)
IS  - 0972-7531 (Linking)
VI  - 25
IP  - 4
DP  - 2018 Dec
TI  - Role of DNA Methylation in Hypobaric Hypoxia-Induced Neurodegeneration and 
      Spatial Memory Impairment.
PG  - 191-200
LID - 10.1159/000490368 [doi]
AB  - Hypobaric hypoxia (HH) is a major stress factor that is associated with 
      physiological, biochemical, molecular and genomic alterations. Brain is the organ 
      that reacts sensitively to oxygen deprivation, which leads to oxidative stress 
      and cognitive function impairment. Our previous studies have reported that 
      downregulation of brain derived neurotrophic factor (BDNF) leads to 
      neurodegeneration and memory impairment. The aim of the present study was to 
      investigate the effect of HH exposure on DNA methylation and its regulation in 
      BDNF expression, neurodegeneration and spatial memory impairment. For this 
      purpose, Sprague Dawley rats were exposed to HH at a simulated altitude of 25,000 
      feet for 14 days. Real-time polymerase chain reaction was used for 
      transcriptional expression of DNA Methyltransferases (DNMTs) including DNMT1, 
      DNMT3a and -DNMT3b, and immunoblotting was used for the translational expression 
      of DNMT1, DNMT3a, DNMT3b, Methyl CpG binding protein 2 (MeCP2), pMeCP2 and BDNF 
      in rat hippocampus. Additionally, neuronal morphology alteration and 
      neurodegeneration in CA1 region of hippocampus were investigated though Cresyl 
      violet (CV) staining and Fluoro-Jade C staining respectively. Results obtained 
      suggested that HH exposure increased the expression of DNMT1 DNMT3b at the mRNA 
      as well as protein level, whereas no significant change was observed in the level 
      of DNMT3a. Furthermore, the level of pMeCP2 and BDNF were significantly 
      decreased; however, the expression level of MeCP2 was significantly increased. 
      The CV and Fluoro-Jade C-positive cells were significantly enhanced in the CA1 
      region of hippocampus in the HH exposed group as compared to unexposed rats. 
      Thus, the present study concluded that HH decreases neuronal activation by the 
      upregulation of DNA methylation and MeCP2 and decreased the expression of pMeCP2, 
      which result in the downregulation of BDNF. The decreased BDNF expression is 
      associated with neuronal loss and spatial memory impairment. This study 
      highlights that DNMT inhibition could be an important therapeutic target for 
      neurodegenerative diseases.
FAU - Kumar, Rahul
AU  - Kumar R
AD  - Neurobiology Division, Defence Institute of Physiology and Allied Science 
      (DIAPS), DRDO, New Delhi, India.
FAU - Jain, Vishal
AU  - Jain V
AD  - Neurophysiology Division, Defence Institute of Physiology and Allied Science 
      (DIAPS), DRDO, New Delhi, India.
FAU - Kushwah, Neetu
AU  - Kushwah N
AD  - Neurobiology Division, Defence Institute of Physiology and Allied Science 
      (DIAPS), DRDO, New Delhi, India.
FAU - Dheer, Aastha
AU  - Dheer A
AD  - Neurobiology Division, Defence Institute of Physiology and Allied Science 
      (DIAPS), DRDO, New Delhi, India.
FAU - Mishra, Kamla Prasad
AU  - Mishra KP
AD  - Directorate General Life Sciences, Defence research Development Organisation 
      (DRDO), Government of India, DRDO Bhawan, Rajaji Marg, New Delhi, India.
FAU - Prasad, Dipti
AU  - Prasad D
AD  - Neurobiology Division, Defence Institute of Physiology and Allied Science 
      (DIAPS), DRDO, New Delhi, India.
FAU - Singh, Shashi Bala
AU  - Singh SB
AD  - Directorate General Life Sciences, Defence research Development Organisation 
      (DRDO), Government of India, DRDO Bhawan, Rajaji Marg, New Delhi, India.
LA  - eng
PT  - Journal Article
DEP - 20180705
PL  - United States
TA  - Ann Neurosci
JT  - Annals of neurosciences
JID - 101523367
PMC - PMC6470337
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - DNA methyltransferase
OT  - Hypobaric hypoxia
OT  - Methyl CpG binding protein 2
OT  - Neurodegeneration
EDAT- 2019/04/20 06:00
MHDA- 2019/04/20 06:01
PMCR- 2018/07/05
CRDT- 2019/04/20 06:00
PHST- 2018/04/09 00:00 [received]
PHST- 2018/05/24 00:00 [accepted]
PHST- 2019/04/20 06:00 [entrez]
PHST- 2019/04/20 06:00 [pubmed]
PHST- 2019/04/20 06:01 [medline]
PHST- 2018/07/05 00:00 [pmc-release]
AID - aon-0025-0191 [pii]
AID - 10.1159/000490368 [doi]
PST - ppublish
SO  - Ann Neurosci. 2018 Dec;25(4):191-200. doi: 10.1159/000490368. Epub 2018 Jul 5.