PMID- 20513372
OWN - NLM
STAT- MEDLINE
DCOM- 20101102
LR  - 20171116
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1347
DP  - 2010 Aug 6
TI  - Analysis of the cholinergic pathology in the P301L tau transgenic pR5 model of 
      tauopathy.
PG  - 111-24
LID - 10.1016/j.brainres.2010.05.076 [doi]
AB  - Cholinergic deafferentation of telencephalon is a major factor contributing to 
      cognitive impairment in Alzheimer's disease. There is evidence that the 
      degeneration of cholinergic fibers which innervate the cortex and hippocampus is 
      due to the development of neurofibrillary tangles in the perikarya of origin. 
      Neurofibrillary tangle formation has been modeled in the transgenic pR5 mouse 
      strain that overexpresses the longest human tau isoform together with the P301L 
      mutation that has been previously identified in familial cases of frontotemporal 
      dementia and parkinsonism linked to chromosome 17 (FTDP-17). To test the 
      suitability of the pR5 model as a model of Alzheimer's disease concerning the 
      cholinergic innervation of the telencephalon, we determined the expression of the 
      human tau transgene and the presence of neurofibrillary changes in the basal 
      nucleus of Meynert, the septal nuclei and the diagonal band of Broca, sources of 
      cholinergic innervation of the cerebral cortex and hippocampus. We found that the 
      cholinergic neurons of these nuclei, despite widespread expression of the human 
      tau transgene, neither expressed human tau nor displayed immunoreactivity with 
      antibodies AT8 and AT180 which recognize hyperphosphorylated tau. 
      Immunoreactivity for choline-acetyl transferase did not reveal significant 
      differences between pR5 mice and non-transgenic littermates in the basal 
      forebrain, cortex and hippocampus. However, in the amygdala dystrophic 
      cholinergic neurites were observed which were not present in non-transgenic mice. 
      Our data show that although pR5 mice develop neurofibrillary lesions, they do not 
      model the degeneration of basal forebrain cholinergic neurons observed in 
      Alzheimer's disease.
CI  - Copyright 2010 Elsevier B.V. All rights reserved.
FAU - Kohler, C
AU  - Kohler C
AD  - Dept. of Anatomy/Neuroanatomy, University Hospital Cologne, Cologne, Germany. 
      c.koehler@uni-koeln.de
FAU - Bista, P
AU  - Bista P
FAU - Gotz, J
AU  - Gotz J
FAU - Schroder, H
AU  - Schroder H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100531
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Bsg protein, mouse)
RN  - 0 (Cholinergic Agents)
RN  - 0 (tau Proteins)
RN  - 136894-56-9 (Basigin)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 2.3.1.6 (Choline O-Acetyltransferase)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Animals
MH  - Basigin/metabolism
MH  - Brain/*pathology
MH  - Choline O-Acetyltransferase/metabolism
MH  - Cholinergic Agents/*metabolism
MH  - Gene Expression Regulation/genetics
MH  - Interneurons/metabolism
MH  - Leucine/*genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Proline/*genetics
MH  - Tauopathies/genetics/*pathology
MH  - tau Proteins/*genetics/metabolism
EDAT- 2010/06/02 06:00
MHDA- 2010/11/03 06:00
CRDT- 2010/06/02 06:00
PHST- 2010/03/26 00:00 [received]
PHST- 2010/05/21 00:00 [revised]
PHST- 2010/05/24 00:00 [accepted]
PHST- 2010/06/02 06:00 [entrez]
PHST- 2010/06/02 06:00 [pubmed]
PHST- 2010/11/03 06:00 [medline]
AID - S0006-8993(10)01280-1 [pii]
AID - 10.1016/j.brainres.2010.05.076 [doi]
PST - ppublish
SO  - Brain Res. 2010 Aug 6;1347:111-24. doi: 10.1016/j.brainres.2010.05.076. Epub 2010 
      May 31.