PMID- 25099302
OWN - NLM
STAT- MEDLINE
DCOM- 20150114
LR  - 20211021
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 131
IP  - 5
DP  - 2014 Dec
TI  - BDNF and Huntingtin protein modifications by manganese: implications for striatal 
      medium spiny neuron pathology in manganese neurotoxicity.
PG  - 655-66
LID - 10.1111/jnc.12926 [doi]
AB  - High levels of manganese (Mn) exposure decrease striatal medium spiny neuron 
      (MSN) dendritic length and spine density, but the mechanism(s) are not known. The 
      Huntingtin (HTT) gene has been functionally linked to cortical brain-derived 
      neurotrophic factor (BDNF) support of striatal MSNs via phosphorylation at serine 
      421. In Huntington's disease, pathogenic CAG repeat expansions of HTT decrease 
      synthesis and disrupt transport of cortical-striatal BDNF, which may contribute 
      to disease, and Mn is a putative environmental modifier of Huntington's disease 
      pathology. Thus, we tested the hypothesis that changes in MSN dendritic 
      morphology Mn due to exposure are associated with decreased BDNF levels and 
      alterations in Htt protein. We report that BDNF levels are decreased in the 
      striatum of Mn-exposed non-human primates and in the cerebral cortex and striatum 
      of mice exposed to Mn. Furthermore, proBDNF and mature BDNF concentrations in 
      primary cortical and hippocampal neuron cultures were decreased by exposure to Mn 
      confirming the in vivo findings. Mn exposure decreased serine 421 phosphorylation 
      of Htt in cortical and hippocampal neurons and increased total Htt levels. These 
      data strongly support the hypothesis that Mn-exposure-related MSN pathology is 
      associated with decreased BDNF trophic support via alterations in Htt.
CI  - (c) 2014 International Society for Neurochemistry.
FAU - Stansfield, Kirstie H
AU  - Stansfield KH
AD  - Department of Environmental Health Sciences, Mailman School of Public Health, 
      Columbia University, New York, New York, USA.
FAU - Bichell, Terry Jo
AU  - Bichell TJ
FAU - Bowman, Aaron B
AU  - Bowman AB
FAU - Guilarte, Tomas R
AU  - Guilarte TR
LA  - eng
GR  - ES009089/ES/NIEHS NIH HHS/United States
GR  - T32 ES007028/ES/NIEHS NIH HHS/United States
GR  - R01 ES016931/ES/NIEHS NIH HHS/United States
GR  - ES016931/ES/NIEHS NIH HHS/United States
GR  - R56 ES010975/ES/NIEHS NIH HHS/United States
GR  - P30 ES009089/ES/NIEHS NIH HHS/United States
GR  - R01 ES010975/ES/NIEHS NIH HHS/United States
GR  - ES010975/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140902
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Htt protein, rat)
RN  - 0 (Huntingtin Protein)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Mtap2 protein, mouse)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 42Z2K6ZL8P (Manganese)
SB  - IM
MH  - Animals
MH  - Brain/cytology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Corpus Striatum/*pathology
MH  - Dendritic Spines/*metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Embryo, Mammalian
MH  - Gene Expression Regulation/drug effects
MH  - Huntingtin Protein
MH  - Manganese/pharmacology
MH  - Manganese Poisoning/*pathology
MH  - Mice
MH  - Microtubule-Associated Proteins/metabolism
MH  - Nerve Tissue Proteins/*metabolism
MH  - Neurons/*ultrastructure
MH  - Nuclear Proteins/*metabolism
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC4296578
MID - NIHMS621006
OTO - NOTNLM
OT  - BDNF
OT  - Huntingtin
OT  - cortical
OT  - manganese
OT  - medium spiny neuron
COIS- Conflicts of interest: The authors have no conflict of interest to declare.
EDAT- 2014/08/08 06:00
MHDA- 2015/01/15 06:00
PMCR- 2015/12/01
CRDT- 2014/08/08 06:00
PHST- 2014/05/08 00:00 [received]
PHST- 2014/07/31 00:00 [revised]
PHST- 2014/08/01 00:00 [accepted]
PHST- 2014/08/08 06:00 [entrez]
PHST- 2014/08/08 06:00 [pubmed]
PHST- 2015/01/15 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - 10.1111/jnc.12926 [doi]
PST - ppublish
SO  - J Neurochem. 2014 Dec;131(5):655-66. doi: 10.1111/jnc.12926. Epub 2014 Sep 2.