PMID- 25153079
OWN - NLM
STAT- MEDLINE
DCOM- 20151112
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 8
DP  - 2014
TI  - Central and systemic responses to methionine-induced hyperhomocysteinemia in 
      mice.
PG  - e105704
LID - 10.1371/journal.pone.0105704 [doi]
LID - e105704
AB  - Hyperhomocysteinemia has been considered a risk factor for neuropsychiatric 
      disorders, but the mechanisms involved in this process have not been completely 
      elucidated. The aim of this study was to analyze the influence of 
      hyperhomocysteinemia induction by methionine supplementation considering 
      different levels and periods of exposure in mice. For this purpose, methionine 
      supplementation at concentrations of 0.5 and 1% were administered in water to 
      increase homocysteinemia in male C57BL/6 mice, and was maintained for 3 time 
      periods (2, 4 and 6 months of treatment). The results from one-carbon metabolism 
      parameters, brain-derived neurotrophic factor (BDNF) concentrations and 
      behavioral evaluation were compared. The 0.5% supplementation was efficient in 
      increasing plasma homocysteine levels after 2 and 6 months. The 1% 
      supplementation, increased plasma homocysteine after 2, 4 and 6 months. Little 
      influence was observed in cysteine and glutathione concentrations. Frontal cortex 
      BDNF levels showed a lack of treatment influence in all periods; only the 
      expected decrease due to increasing age was observed. Moreover, the only 
      behavioral alteration observed using a novel object recognition task was that 
      which was expected with increasing age. We found that responses to 
      hyperhomocysteinemia varied based on how it was reached, and the length of 
      toxicity. Moreover, hyperhomocysteinemia can affect the normal pattern of one 
      carbon metabolism during age increase in mice. These findings allow the 
      establishment of a reliable animal model for studies in this field.
FAU - de Rezende, Marina Mastelaro
AU  - de Rezende MM
AD  - Department of Psychobiology, Universidade Federal de Sao Paulo, Sao Paulo, 
      Brazil.
FAU - D'Almeida, Vania
AU  - D'Almeida V
AD  - Department of Psychobiology, Universidade Federal de Sao Paulo, Sao Paulo, 
      Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140825
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - AE28F7PNPL (Methionine)
RN  - GAN16C9B8O (Glutathione)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Brain/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cysteine/blood
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Glutathione/blood
MH  - Homocysteine/blood
MH  - Hyperhomocysteinemia/chemically induced/*metabolism
MH  - Male
MH  - Methionine/*administration & dosage
MH  - Mice
MH  - Motor Activity/drug effects
MH  - Recognition, Psychology/drug effects
MH  - Time Factors
PMC - PMC4143291
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/08/26 06:00
MHDA- 2015/11/13 06:00
PMCR- 2014/08/25
CRDT- 2014/08/26 06:00
PHST- 2014/04/27 00:00 [received]
PHST- 2014/07/22 00:00 [accepted]
PHST- 2014/08/26 06:00 [entrez]
PHST- 2014/08/26 06:00 [pubmed]
PHST- 2015/11/13 06:00 [medline]
PHST- 2014/08/25 00:00 [pmc-release]
AID - PONE-D-14-18892 [pii]
AID - 10.1371/journal.pone.0105704 [doi]
PST - epublish
SO  - PLoS One. 2014 Aug 25;9(8):e105704. doi: 10.1371/journal.pone.0105704. 
      eCollection 2014.