PMID- 19198115
OWN - NLM
STAT- MEDLINE
DCOM- 20090408
LR  - 20190917
IS  - 0009-918X (Print)
IS  - 0009-918X (Linking)
VI  - 48
IP  - 11
DP  - 2008 Nov
TI  - [Neurodegeneration and inflammation: analysis of a FTDP-17 model mouse].
PG  - 910-2
AB  - Filamentous tau inclusions are hallmarks of Alzheimer's disease (AD) and related 
      tauopathies, and the discovery of mutations in the tau gene in frontotemporal 
      dementia and parkinsonism linked to chromosome 17 (FTDP-17) constitutes 
      convincing evidence that tau proteins play a key role in the pathogenesis of 
      neurodegenerative disorders. To investigate the pathomechanism of tauopathies, we 
      generated and studied P301S mutant human tau transgenic mice (line PS19). 
      Filamentous tau lesions developed in PS19 mice at 6-months of age, and 
      progressively accumulated in association with striking neuron loss as well as 
      hippocampal and entorhinal cortical atrophy by 9-12 months of age. Remarkably, 
      hippocampal synapse loss and impaired synaptic function were detected in 3 month 
      old PS19 mice before fibrillary tau tangles emerged. Prominent microglial 
      activation and proinflammatory cytokine expressions in neurons also preceded 
      tangle formation. Importantly, immunosuppression of young PS19 mice with FK506 
      attenuated tau pathology, thereby linking neuroinflammation to early progression 
      of tauopathies. Recently, an anti-inflammatory function of acetylcholine (ACh) 
      has been reported, suggesting that synaptic dysfunction might accelerate 
      neuroinflammatory reaction by depletion of ACH. To investigate this, we 
      administered donepezil (DZ), an ACh-esterase inhibitor, and trihexiphenidyl (TP), 
      an anti-cholinergic agent to PS19 mice. Interestingly, DZ ameliorated but TP 
      deteriorated microglial activation, tau pathology and neuronal loss, indicating 
      the ACh level in the brain might play roles in not only neurotransmission, but 
      also suppressing neuroinflammation in the brain.
FAU - Yoshiyama, Yasumasa
AU  - Yoshiyama Y
AD  - Department of Neurology, Laboratory for Neurodegenerative Disorder Research, 
      Clinical Research Center, Chiba-East National Hospital.
LA  - jpn
PT  - Journal Article
PT  - Review
PL  - Japan
TA  - Rinsho Shinkeigaku
JT  - Rinsho shinkeigaku = Clinical neurology
JID - 0417466
RN  - 0 (Amyloid)
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Indans)
RN  - 0 (MAPT protein, human)
RN  - 0 (Piperidines)
RN  - 0 (tau Proteins)
RN  - 8SSC91326P (Donepezil)
RN  - N9YNS0M02X (Acetylcholine)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Acetylcholine/metabolism/physiology
MH  - Amyloid/metabolism/toxicity
MH  - Animals
MH  - Brain/metabolism
MH  - Cholinesterase Inhibitors
MH  - Disease Models, Animal
MH  - Donepezil
MH  - Humans
MH  - Immunosuppressive Agents/therapeutic use
MH  - Indans/pharmacology/therapeutic use
MH  - Inflammation/*genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Microglia/physiology
MH  - Mutation
MH  - Neurodegenerative Diseases/drug therapy/*genetics/pathology
MH  - Piperidines/pharmacology/therapeutic use
MH  - Synapses/pathology
MH  - Tacrolimus/therapeutic use
MH  - tau Proteins/*genetics
RF  - 8
EDAT- 2009/02/10 09:00
MHDA- 2009/04/09 09:00
CRDT- 2009/02/10 09:00
PHST- 2009/02/10 09:00 [entrez]
PHST- 2009/02/10 09:00 [pubmed]
PHST- 2009/04/09 09:00 [medline]
AID - 10.5692/clinicalneurol.48.910 [doi]
PST - ppublish
SO  - Rinsho Shinkeigaku. 2008 Nov;48(11):910-2. doi: 10.5692/clinicalneurol.48.910.