PMID- 35752846
OWN - NLM
STAT- MEDLINE
DCOM- 20220628
LR  - 20220727
IS  - 1868-7083 (Electronic)
IS  - 1868-7075 (Print)
IS  - 1868-7075 (Linking)
VI  - 14
IP  - 1
DP  - 2022 Jun 25
TI  - Mitochondrial DNA methylation profiling of the human prefrontal cortex and 
      nucleus accumbens: correlations with aging and drug use.
PG  - 79
LID - 10.1186/s13148-022-01300-z [doi]
LID - 79
AB  - BACKGROUND: Despite the brain's high demand for energy, research on its 
      epigenetics focuses on nuclear methylation, and much of the mitochondrial DNA 
      methylation remains seldom investigated. With a focus on the nucleus accumbens 
      (NAcc) and the prefrontal cortex (PFC), we aimed to identify the mitochondrial 
      methylation signatures for (1) distinguishing the two brain areas, (2) 
      correlating with aging, and (3) reflecting the influence of illicit drugs on the 
      brain. RESULT: We collected the brain tissue in the NAcc and the PFC from the 
      deceased individuals without (n = 39) and with (n = 14) drug use and used 
      whole-genome bisulfite sequencing to cover cytosine sites in the mitochondrial 
      genome. We first detected differential methylations between the NAcc and the PFC 
      in the nonusers group (P = 3.89 x 10(-9)). These function-related methylation 
      differences diminished in the drug use group due to the selective alteration in 
      the NAcc. Then, we found the correlation between the methylation levels and the 
      chronological ages in the nonusers group (R(2) = 0.34 in the NAcc and 0.37 in the 
      PFC). The epigenetic clocks in illicit drug users, especially in the ketamine 
      users, were accelerated in both brain regions by comparison with the nonusers. 
      Finally, we summarized the effect of the illicit drugs on the methylation, which 
      could significantly differentiate the drug users from the nonusers (AUC = 0.88 in 
      the NAcc, AUC = 0.94 in the PFC). CONCLUSION: The mitochondrial methylations were 
      different between different brain areas, generally accumulated with aging, and 
      sensitive to the effects of illicit drugs. We believed this is the first report 
      to elucidate comprehensively the importance of mitochondrial DNA methylation in 
      human brain.
CI  - (c) 2022. The Author(s).
FAU - Huang, Chia-Hung
AU  - Huang CH
AD  - Forensic Biology Division, Institute of Forensic Medicine, Ministry of Justice, 
      New Taipei City, Taiwan.
AD  - Forensic Pathology Division, Institute of Forensic Medicine, Ministry of Justice, 
      New Taipei City, Taiwan.
AD  - Institute of Epidemiology and Preventive Medicine, National Taiwan University, 
      Taipei, Taiwan.
FAU - Chang, Man-Chen
AU  - Chang MC
AD  - Forensic Biology Division, Institute of Forensic Medicine, Ministry of Justice, 
      New Taipei City, Taiwan.
FAU - Lai, Yung-Chun
AU  - Lai YC
AD  - Forensic Biology Division, Institute of Forensic Medicine, Ministry of Justice, 
      New Taipei City, Taiwan.
FAU - Lin, Chun-Yen
AU  - Lin CY
AD  - Forensic Biology Division, Institute of Forensic Medicine, Ministry of Justice, 
      New Taipei City, Taiwan.
FAU - Hsu, Cho-Hsien
AU  - Hsu CH
AD  - Forensic Pathology Division, Institute of Forensic Medicine, Ministry of Justice, 
      New Taipei City, Taiwan.
FAU - Tseng, Bo-Yuan
AU  - Tseng BY
AD  - Forensic Pathology Division, Institute of Forensic Medicine, Ministry of Justice, 
      New Taipei City, Taiwan.
FAU - Hsiao, Chuhsing Kate
AU  - Hsiao CK
AD  - Institute of Epidemiology and Preventive Medicine, National Taiwan University, 
      Taipei, Taiwan.
FAU - Lu, Tzu-Pin
AU  - Lu TP
AD  - Institute of Epidemiology and Preventive Medicine, National Taiwan University, 
      Taipei, Taiwan.
FAU - Yu, Sung-Liang
AU  - Yu SL
AD  - Department of Clinical Laboratory Sciences and Medical Biotechnology, College of 
      Medicine, National Taiwan University, Taipei, Taiwan.
FAU - Hsieh, Sung-Tsang
AU  - Hsieh ST
AD  - Department of Anatomy and Cell Biology, College of Medicine, National Taiwan 
      University, Taipei, Taiwan.
AD  - Department of Neurology, College of Medicine and National Taiwan University 
      Hospital, National Taiwan University, Taipei, Taiwan.
FAU - Chen, Wei J
AU  - Chen WJ
AD  - Institute of Epidemiology and Preventive Medicine, National Taiwan University, 
      Taipei, Taiwan. wjchen@ntu.edu.tw.
AD  - Department of Psychiatry, College of Medicine and National Taiwan University 
      Hospital, National Taiwan University, Taipei, Taiwan. wjchen@ntu.edu.tw.
AD  - Center for Neuropsychiatric Research, National Health Research Institutes, 
      Zhunan, Miaoli County, Taiwan. wjchen@ntu.edu.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220625
PL  - Germany
TA  - Clin Epigenetics
JT  - Clinical epigenetics
JID - 101516977
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Illicit Drugs)
SB  - IM
MH  - Aging/genetics
MH  - DNA Methylation
MH  - DNA, Mitochondrial/genetics
MH  - Humans
MH  - *Illicit Drugs/pharmacology
MH  - *Nucleus Accumbens
MH  - Prefrontal Cortex
PMC - PMC9233363
OTO - NOTNLM
OT  - Aging
OT  - Epigenetic
OT  - Illicit drug
OT  - Nucleus accumbens
OT  - Prefrontal cortex
OT  - Whole-mitochondrial-genome bisulfite sequencing
COIS- The authors declare that they have no competing interests.
EDAT- 2022/06/26 06:00
MHDA- 2022/06/29 06:00
PMCR- 2022/06/25
CRDT- 2022/06/25 23:33
PHST- 2022/03/01 00:00 [received]
PHST- 2022/06/20 00:00 [accepted]
PHST- 2022/06/25 23:33 [entrez]
PHST- 2022/06/26 06:00 [pubmed]
PHST- 2022/06/29 06:00 [medline]
PHST- 2022/06/25 00:00 [pmc-release]
AID - 10.1186/s13148-022-01300-z [pii]
AID - 1300 [pii]
AID - 10.1186/s13148-022-01300-z [doi]
PST - epublish
SO  - Clin Epigenetics. 2022 Jun 25;14(1):79. doi: 10.1186/s13148-022-01300-z.