PMID- 24140565
OWN - NLM
STAT- MEDLINE
DCOM- 20140731
LR  - 20220110
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 258
DP  - 2014 Jan 1
TI  - Tripchlorolide improves age-associated cognitive deficits by reversing 
      hippocampal synaptic plasticity impairment and NMDA receptor dysfunction in SAMP8 
      mice.
PG  - 8-18
LID - S0166-4328(13)00618-9 [pii]
LID - 10.1016/j.bbr.2013.10.010 [doi]
AB  - Deficits in cognition and performance accompanying age-related neurodegenerative 
      diseases such as Alzheimer's disease (AD) are closely associated with the 
      impairment of synaptic plasticity. Here, using a mouse model of 
      senescence-accelerated P8 (SAMP8), we reported the role of tripchlorolide (T4), 
      an extract of the natural herb Tripterygium wilfordii Hook F, in improving 
      cognitive deficits and promoting the long-term potentiation (LTP) of hippocampal 
      slices via the N-methyl-D-aspartate receptor (NMDAR)-dependent signaling pathway. 
      Our results demonstrated that chronic administration of T4 at low doses (0.25, 
      1.0, or 4.0 mug/kg per day, injected intraperitoneally for 75 days) significantly 
      improved learning and memory function in aged SAMP8 mice, as indicated by a chain 
      of behavioral tests including the Y-maze and Morris water maze. Additionally, T4 
      reversed the impaired LTP in hippocampal CA1 regions of SAMP8 mice in a 
      dose-dependent manner. Moreover, it upregulated the levels of phospho-NMDAR1, 
      postsynaptic density-95 (PSD-95), phospho-calcium-calmodulin dependent kinase II 
      (CaMKII), phospho-CREB and brain derived neurotrophic factor (BDNF) in the 
      hippocampus. This indicates that T4 prevents the impairment of NMDAR-mediated 
      synaptic plasticity-related signal molecules. At optimal doses, T4 did not show 
      significant side-effects on blood counts, blood biochemical measures, or survival 
      of the mice. This novel mechanism in reversing age-related synaptic dysfunction 
      and NMDAR functional deficits suggests that T4 can halt the manifestation of a 
      key early-stage event in AD. With the consideration of SAMP8 mice as a model to 
      develop therapeutic interventions for AD, our findings provide new insight into 
      the clinical application of tripchlorolide in AD treatment.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Lin, Nan
AU  - Lin N
AD  - Department of Neurology, Fujian Institute of Geriatrics, Fujian Medical 
      University Union Hospital, 29 Xinquan Road, Fuzhou 350001, China; Key Laboratory 
      of Brain Aging and Neurodegenerative Disease, Fujian Key Laboratory of Molecular 
      Neurology, Fujian Medical University, 29 Xinquan Road, Fuzhou 350001, China.
FAU - Pan, Xiao-dong
AU  - Pan XD
FAU - Chen, Ai-qin
AU  - Chen AQ
FAU - Zhu, Yuan-gui
AU  - Zhu YG
FAU - Wu, Ming
AU  - Wu M
FAU - Zhang, Jing
AU  - Zhang J
FAU - Chen, Xiao-chun
AU  - Chen XC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131017
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Diterpenes)
RN  - 0 (Phenanthrenes)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 132368-08-2 (tripchlorolide)
SB  - IM
EIN - Behav Brain Res. 2022 Mar 12;421:113734. PMID: 35007960
MH  - Aging/drug effects/metabolism
MH  - Animals
MH  - Cognition/*drug effects
MH  - Cognition Disorders/*drug therapy/metabolism/physiopathology
MH  - Diterpenes/*pharmacology/therapeutic use
MH  - Hippocampus/*drug effects/physiopathology
MH  - Male
MH  - Maze Learning/drug effects
MH  - Mice
MH  - Neuronal Plasticity/*drug effects/physiology
MH  - Phenanthrenes/*pharmacology/therapeutic use
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Synapses/*drug effects/physiology
OTO - NOTNLM
OT  - AD
OT  - Aging
OT  - Alzheimer's Disease
OT  - BDNF
OT  - CREB
OT  - CaMKII
OT  - Cognition
OT  - EPSPs
OT  - LTP
OT  - Long-term potentiation
OT  - MWM
OT  - Morris water maze
OT  - N-methyl-d-aspartate receptor
OT  - NMDA receptor
OT  - NMDAR
OT  - PSD-95
OT  - SAMP8
OT  - Synaptic plasticity
OT  - T(4)
OT  - Tripchlorolide
OT  - brain-derived neurotrophic factor
OT  - calcium/calmodulin-dependent protein kinase II
OT  - cyclic AMP-response element binding protein
OT  - excitatory postsynaptic potentials
OT  - long-term potentiation
OT  - postsynaptic density-95
OT  - senescence-accelerated mouse Prone 8 SAMR1
OT  - tripchlorolide
EDAT- 2013/10/22 06:00
MHDA- 2014/08/01 06:00
CRDT- 2013/10/22 06:00
PHST- 2013/06/04 00:00 [received]
PHST- 2013/09/29 00:00 [revised]
PHST- 2013/10/03 00:00 [accepted]
PHST- 2013/10/22 06:00 [entrez]
PHST- 2013/10/22 06:00 [pubmed]
PHST- 2014/08/01 06:00 [medline]
AID - S0166-4328(13)00618-9 [pii]
AID - 10.1016/j.bbr.2013.10.010 [doi]
PST - ppublish
SO  - Behav Brain Res. 2014 Jan 1;258:8-18. doi: 10.1016/j.bbr.2013.10.010. Epub 2013 
      Oct 17.