PMID- 25446926
OWN - NLM
STAT- MEDLINE
DCOM- 20150824
LR  - 20161125
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 745
DP  - 2014 Dec 15
TI  - Carnitine congener mildronate protects against stress- and haloperidol-induced 
      impairment in memory and brain protein expression in rats.
PG  - 76-83
LID - S0014-2999(14)00721-3 [pii]
LID - 10.1016/j.ejphar.2014.10.014 [doi]
AB  - The present study investigates the efficacy of mildronate, a carnitine congener, 
      to protect stress and haloperidol-induced impairment of memory in rats and the 
      expression of brain protein biomarkers involved in synaptic plasticity, such as 
      brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate 
      decarboxylase 67 (GAD67). Two amnesia models were used: 2h immobilization stress 
      and 3-week haloperidol treatment. Stress caused memory impairment in the passive 
      avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and 
      striatal tissues that was completely inhibited by mildronate. Mildronate 
      decreased the level of GAD67 (but not acetylcholine esterase) expression by 
      stress. Haloperidol decrease by a third hippocampal BDNF and acetylcholine 
      esterase (but not GAD67) expression, which was normalized by mildronate; it also 
      reversed the haloperidol-induced memory impairment in Barnes test. The results 
      suggest the usefulness of mildronate as protector against neuronal disturbances 
      caused by stress or haloperidol.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Beitnere, Ulrika
AU  - Beitnere U
AD  - Department of Pharmacology, Faculty of Medicine, University of Latvia, 19, Raina 
      blv., Riga LV-1586, Latvia.
FAU - Dzirkale, Zane
AU  - Dzirkale Z
AD  - Department of Pharmacology, Faculty of Medicine, University of Latvia, 19, Raina 
      blv., Riga LV-1586, Latvia.
FAU - Isajevs, Sergejs
AU  - Isajevs S
AD  - Department of Pathology, Faculty of Medicine, University of Latvia, 19, Raina 
      blv., Riga, LV-1586, Latvia; Riga East University Hospital, Center of Pathology, 
      2 Hipokrata str., LV-1038 Riga, Latvia.
FAU - Rumaks, Juris
AU  - Rumaks J
AD  - Department of Pharmacology, Faculty of Medicine, University of Latvia, 19, Raina 
      blv., Riga LV-1586, Latvia.
FAU - Svirskis, Simons
AU  - Svirskis S
AD  - Department of Pharmacology, Faculty of Medicine, University of Latvia, 19, Raina 
      blv., Riga LV-1586, Latvia.
FAU - Klusa, Vija
AU  - Klusa V
AD  - Department of Pharmacology, Faculty of Medicine, University of Latvia, 19, Raina 
      blv., Riga LV-1586, Latvia. Electronic address: vijaklus@latnet.lv.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141017
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Methylhydrazines)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 73H7UDN6EC (3-(2,2,2-trimethylhydrazine)propionate)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
RN  - EC 3.1.1.7 (Ache protein, rat)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
RN  - EC 4.1.1.15 (glutamate decarboxylase 1)
RN  - J6292F8L3D (Haloperidol)
RN  - S7UI8SM58A (Carnitine)
SB  - IM
MH  - Acetylcholinesterase/metabolism
MH  - Animals
MH  - Avoidance Learning/drug effects/physiology
MH  - Biomarkers/metabolism
MH  - Brain/*drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Carnitine/analogs & derivatives/pharmacology
MH  - GPI-Linked Proteins/metabolism
MH  - Glutamate Decarboxylase/metabolism
MH  - Haloperidol/toxicity
MH  - Male
MH  - Maze Learning/drug effects/physiology
MH  - Memory/*drug effects/physiology
MH  - Methylhydrazines/*pharmacology
MH  - Nerve Tissue Proteins/metabolism
MH  - Neuroprotective Agents/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Stress, Physiological
OTO - NOTNLM
OT  - Haloperidol
OT  - Haloperidol (PubChem CID: 3559)
OT  - Memory
OT  - Mildronate
OT  - Mildronate (PubChem CID: 123868)
OT  - Protein expression
OT  - Stress
EDAT- 2014/12/03 06:00
MHDA- 2015/08/25 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/05/20 00:00 [received]
PHST- 2014/10/08 00:00 [revised]
PHST- 2014/10/08 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/08/25 06:00 [medline]
AID - S0014-2999(14)00721-3 [pii]
AID - 10.1016/j.ejphar.2014.10.014 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2014 Dec 15;745:76-83. doi: 10.1016/j.ejphar.2014.10.014. Epub 
      2014 Oct 17.