PMID- 25560396
OWN - NLM
STAT- MEDLINE
DCOM- 20160105
LR  - 20181113
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 172
IP  - 9
DP  - 2015 May
TI  - MPTP-induced changes in hippocampal synaptic plasticity and memory are prevented 
      by memantine through the BDNF-TrkB pathway.
PG  - 2354-68
LID - 10.1111/bph.13061 [doi]
AB  - BACKGROUND AND PURPOSE: Mild cognitive deficit in early Parkinson's disease (PD) 
      has been widely studied. Here we have examined the effects of memantine in 
      preventing memory deficit in experimental PD models and elucidated some of the 
      underlying mechanisms. EXPERIMENTAL APPROACHES: I.p. injection of 1-methyl-4- 
      phenyl-1,2,3,6-tetrahydro pyridine (MPTP) in C57BL/6 mice was used to produce 
      models of PD. We used behavioural tasks to test memory. In vitro, we used slices 
      of hippocampus, with electrophysiological, Western blotting, real time PCR, elisa 
      and immunochemical techniques. KEY RESULTS: Following MPTP injection, long-term 
      memory was impaired and these changes were prevented by pre-treatment with 
      memantine. In hippocampal slices from MPTP treated mice, long-term potentiation 
      (LTP) -induced by theta burst stimulation (10 bursts, 4 pulses) was decreased, while 
      long-term depression (LTD) induced by low-frequency stimulation (1 Hz, 900 
      pulses) was enhanced, compared with control values. A single dose of memantine 
      (i.p., 10 mg.kg(-1) ) reversed the decreased LTP and the increased LTD in this PD 
      model. Activity-dependent changes in tyrosine kinase receptor B (TrkB), ERK and 
      brain-derived neurotrophic factor (BDNF) expression were decreased in slices from 
      mice after MPTP treatment. These effects were reversed by pretreatment with 
      memantine. Incubation of slices in vitro with 1-methyl-4-phenylpyridinium (MPP(+) 
      ) decreased depolarization-induced expression of BDNF. This effect was prevented 
      by pretreatment of slices with memantine or with calpain inhibitor III, 
      suggesting the involvement of an overactivated calcium signalling pathway. 
      CONCLUSIONS AND IMPLICATIONS: Memantine should be useful in preventing loss of 
      memory and hippocampal synaptic plasticity in PD models.
CI  - (c) 2015 The British Pharmacological Society.
FAU - Zhu, Guoqi
AU  - Zhu G
AD  - Key Laboratory of Xin'An Medicine, Ministry of Education, Anhui University of 
      Traditional Chinese Medicine, Hefei, China.
FAU - Li, Junyao
AU  - Li J
FAU - He, Ling
AU  - He L
FAU - Wang, Xuncui
AU  - Wang X
FAU - Hong, Xiaoqi
AU  - Hong X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150326
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Antiparkinson Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Membrane Glycoproteins)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
RN  - EC 2.7.10.1 (Ntrk2 protein, mouse)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - R865A5OY8J (1-Methyl-4-phenylpyridinium)
RN  - W8O17SJF3T (Memantine)
SB  - IM
MH  - *1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
MH  - 1-Methyl-4-phenylpyridinium/pharmacology
MH  - Animals
MH  - Antiparkinson Agents/*pharmacology
MH  - Behavior, Animal/*drug effects
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Calcium Signaling/drug effects
MH  - Disease Models, Animal
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Hippocampus/*drug effects/metabolism/physiopathology
MH  - In Vitro Techniques
MH  - Male
MH  - Memantine/*pharmacology
MH  - Membrane Glycoproteins/*metabolism
MH  - Memory Disorders/chemically induced/metabolism/physiopathology/*prevention & 
      control/psychology
MH  - Memory, Long-Term/*drug effects
MH  - Mice, Inbred C57BL
MH  - Neuronal Plasticity/*drug effects
MH  - Parkinsonian Disorders/chemically induced/metabolism/physiopathology/*prevention 
      & control/psychology
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Synapses/*drug effects/metabolism
MH  - Time Factors
PMC - PMC4403099
EDAT- 2015/01/07 06:00
MHDA- 2016/01/06 06:00
PMCR- 2016/05/01
CRDT- 2015/01/07 06:00
PHST- 2014/07/26 00:00 [received]
PHST- 2014/12/11 00:00 [revised]
PHST- 2014/12/18 00:00 [accepted]
PHST- 2015/01/07 06:00 [entrez]
PHST- 2015/01/07 06:00 [pubmed]
PHST- 2016/01/06 06:00 [medline]
PHST- 2016/05/01 00:00 [pmc-release]
AID - 10.1111/bph.13061 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2015 May;172(9):2354-68. doi: 10.1111/bph.13061. Epub 2015 Mar 
      26.