PMID- 29882218
OWN - NLM
STAT- MEDLINE
DCOM- 20190227
LR  - 20190227
IS  - 1749-6632 (Electronic)
IS  - 0077-8923 (Linking)
VI  - 1431
IP  - 1
DP  - 2018 Nov
TI  - Methylene blue protects dopaminergic neurons against MPTP-induced neurotoxicity 
      by upregulating brain-derived neurotrophic factor.
PG  - 58-71
LID - 10.1111/nyas.13870 [doi]
AB  - The relatively old, yet clinically used, drug methylene blue (MB) is known to 
      possess neuroprotective properties by reducing aggregated proteins, augmenting 
      the antioxidant response, and enhancing mitochondrial function and survival in 
      various models of neurodegenerative diseases. In this study, we aimed to examine 
      the effects of MB in Parkinson's disease (PD) in vivo and in vitro models by 
      using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 
      (MPTP)/1-methyl-4-phenylpyridinium (MPP(+) ) with a focus on possible effects on 
      induction of neurotrophic factors. Our results indicate that pretreatment with MB 
      significantly attenuated MPTP-induced loss of dopaminergic neurons, glial cell 
      activation, and depletion of dopamine. We also found that MB upregulated 
      brain-derived neurotrophic factor (BDNF) and activated its downstream signaling 
      pathways, suggesting that BDNF might be a contributor to MB-associated 
      neuroprotection. Specific inhibition of the BDNF receptor or extracellular 
      signal-regulated kinase (Erk) reversed the MB-mediated protection against MPP(+) 
      toxicity, thus implying a role for BDNF and the Erk pathway in the 
      neuroprotective effects. Taken together, our data suggest that MB protects 
      neurons from MPTP neurotoxicity via induction of BDNF. Further study to determine 
      whether MB preserves dopaminergic neurons in the brains of PD patients is 
      warranted.
CI  - (c) 2018 New York Academy of Sciences.
FAU - Bhurtel, Sunil
AU  - Bhurtel S
AD  - College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
FAU - Katila, Nikita
AU  - Katila N
AD  - College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
FAU - Neupane, Sabita
AU  - Neupane S
AD  - College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
FAU - Srivastav, Sunil
AU  - Srivastav S
AD  - College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
FAU - Park, Pil-Hoon
AU  - Park PH
AD  - College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
FAU - Choi, Dong-Young
AU  - Choi DY
AD  - College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180607
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - T42P99266K (Methylene Blue)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Disease Models, Animal
MH  - Dopaminergic Neurons/*drug effects/metabolism
MH  - MPTP Poisoning/metabolism/*prevention & control
MH  - Male
MH  - Methylene Blue/*pharmacology/therapeutic use
MH  - Mice
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - Phosphorylation/drug effects
MH  - Signal Transduction/drug effects
MH  - Tyrosine 3-Monooxygenase/metabolism
MH  - Up-Regulation/*drug effects
OTO - NOTNLM
OT  - BDNF
OT  - MPTP
OT  - Parkinson's disease
OT  - methylene blue
OT  - tropomyosin receptor kinase B
EDAT- 2018/06/09 06:00
MHDA- 2019/02/28 06:00
CRDT- 2018/06/09 06:00
PHST- 2017/12/29 00:00 [received]
PHST- 2018/04/30 00:00 [revised]
PHST- 2018/05/07 00:00 [accepted]
PHST- 2018/06/09 06:00 [pubmed]
PHST- 2019/02/28 06:00 [medline]
PHST- 2018/06/09 06:00 [entrez]
AID - 10.1111/nyas.13870 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2018 Nov;1431(1):58-71. doi: 10.1111/nyas.13870. Epub 2018 Jun 
      7.