PMID- 26057356
OWN - NLM
STAT- MEDLINE
DCOM- 20160614
LR  - 20150902
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 292
DP  - 2015 Oct 1
TI  - Betaine prevents homocysteine-induced memory impairment via matrix 
      metalloproteinase-9 in the frontal cortex.
PG  - 36-43
LID - S0166-4328(15)30032-2 [pii]
LID - 10.1016/j.bbr.2015.06.004 [doi]
AB  - Betaine plays important roles that include acting as a methyl donor and 
      converting homocysteine (Hcy) to methionine. Elevated plasma Hcy levels are known 
      as hyperhomocysteinemia (HHcy) and contribute to impairments of learning and 
      memory. Although it is commonly known that betaine plays an important role in Hcy 
      metabolism, the effects of betaine on Hcy-induced memory impairment have not been 
      investigated. Previously, we demonstrated the beneficial effects of betaine on 
      acute stress and lipopolysaccharide-induced memory impairment. In the present 
      study, we investigated whether betaine ameliorates Hcy-induced memory impairment 
      and the underlying mechanisms of this putative effect. Mice were treated with Hcy 
      (0.162mg/kg, s.c.) twice a day for nine days, and betaine (25mg/kg, s.c.) was 
      administered 30min before the Hcy injections. The memory functions were evaluated 
      using a spontaneous alternation performance test (Y-maze) at seven days and a 
      step-down type passive avoidance test (SD) at nine and ten days after Hcy 
      injection. We found that betaine suppressed the memory impairment induced by 
      repeated Hcy injections. However, the blood concentrations of Hcy were 
      significantly increased in the Hcy-treated mice immediately after the passive 
      avoidance test, and betaine did not prevent this increase. Furthermore, Hcy 
      induces redox stress in part by activating matrix metalloproteinase-9 (MMP-9), 
      which leads to BBB dysfunction. Therefore, we tested whether betaine affected 
      MMP-9 activity. Interestingly, treatment with betaine significantly inhibited 
      Hcy-induced MMP-9 activity in the frontal cortex but not in the hippocampus after 
      acute Hcy injection. These results suggest that the changes in MMP-9 activity 
      after betaine treatment might have been partially responsible for the 
      amelioration of the memory deficits and that MMP-9 might be a candidate 
      therapeutic target for HHcy.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Kunisawa, K
AU  - Kunisawa K
AD  - Department of Chemical Pharmacology, Faculty of Pharmacy, Graduate School of 
      Pharmacy, Meijo University, Nagoya, Japan.
FAU - Nakashima, N
AU  - Nakashima N
AD  - Department of Chemical Pharmacology, Faculty of Pharmacy, Graduate School of 
      Pharmacy, Meijo University, Nagoya, Japan.
FAU - Nagao, M
AU  - Nagao M
AD  - Department of Chemical Pharmacology, Faculty of Pharmacy, Graduate School of 
      Pharmacy, Meijo University, Nagoya, Japan.
FAU - Nomura, T
AU  - Nomura T
AD  - Department of Chemical Pharmacology, Faculty of Pharmacy, Graduate School of 
      Pharmacy, Meijo University, Nagoya, Japan.
FAU - Kinoshita, S
AU  - Kinoshita S
AD  - Department of Chemical Pharmacology, Faculty of Pharmacy, Graduate School of 
      Pharmacy, Meijo University, Nagoya, Japan.
FAU - Hiramatsu, M
AU  - Hiramatsu M
AD  - Department of Chemical Pharmacology, Faculty of Pharmacy, Graduate School of 
      Pharmacy, Meijo University, Nagoya, Japan; Laboratory of Neuropsychopharmacology, 
      Graduate School of Environmental and Human Sciences, Meijo University, Nagoya, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150606
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Lipopolysaccharides)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 3SCV180C9W (Betaine)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Betaine/*pharmacology
MH  - Drug Interactions
MH  - Frontal Lobe/*drug effects/enzymology
MH  - Homocysteine/antagonists & inhibitors/*pharmacology
MH  - Hyperhomocysteinemia
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - Matrix Metalloproteinase 9/*metabolism
MH  - Memory Disorders/*chemically induced/enzymology/*prevention & control
MH  - Mice
OTO - NOTNLM
OT  - Betaine
OT  - Frontal cortex
OT  - Hcy
OT  - Homocysteine
OT  - MMP-9
OT  - Matrix metalloproteinase-9
OT  - Memory
EDAT- 2015/06/10 06:00
MHDA- 2016/06/15 06:00
CRDT- 2015/06/10 06:00
PHST- 2015/02/18 00:00 [received]
PHST- 2015/05/29 00:00 [revised]
PHST- 2015/06/03 00:00 [accepted]
PHST- 2015/06/10 06:00 [entrez]
PHST- 2015/06/10 06:00 [pubmed]
PHST- 2016/06/15 06:00 [medline]
AID - S0166-4328(15)30032-2 [pii]
AID - 10.1016/j.bbr.2015.06.004 [doi]
PST - ppublish
SO  - Behav Brain Res. 2015 Oct 1;292:36-43. doi: 10.1016/j.bbr.2015.06.004. Epub 2015 
      Jun 6.