PMID- 22177996
OWN - NLM
STAT- MEDLINE
DCOM- 20120326
LR  - 20211021
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 233
IP  - 2
DP  - 2012 Feb
TI  - Frontotemporal lobar degeneration-related proteins induce only subtle 
      memory-related deficits when bilaterally overexpressed in the dorsal hippocampus.
PG  - 807-14
LID - 10.1016/j.expneurol.2011.12.002 [doi]
AB  - Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that 
      involves cognitive decline and dementia. To model the hippocampal 
      neurodegeneration and memory-related behavioral impairment that occurs in FTLD 
      and other tau and TDP-43 proteinopathy diseases, we used an adeno-associated 
      virus serotype 9 (AAV9) vector to induce bilateral expression of either 
      microtubule-associated protein tau or transactive response DNA binding protein 43 
      kDa (TDP-43) in adult rat dorsal hippocampus. Human wild-type forms of tau or 
      TDP-43 were expressed. The vectors/doses were designed for moderate expression 
      levels within neurons. Rats were evaluated for acquisition and retention in the 
      Morris water task over 12 weeks after gene transfer. Neither vector altered 
      acquisition performance compared to controls. In measurements of retention, there 
      was impairment in the TDP-43 group. Histological examination revealed specific 
      loss of dentate gyrus granule cells and concomitant gliosis proximal to the 
      injection site in the TDP-43 group, with shrinkage of the dorsal hippocampus. 
      Despite specific tau pathology, the tau gene transfer surprisingly did not cause 
      obvious neuronal loss or behavioral impairment. The data demonstrate that TDP-43 
      produced mild behavioral impairment and hippocampal neurodegeneration in rats, 
      whereas tau did not. The models could be of value for studying mechanisms of FTLD 
      and other diseases with tau and TDP-43 pathology in the hippocampus including 
      Alzheimer's disease, with relevance to early stage mild impairment.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Dayton, Robert D
AU  - Dayton RD
AD  - Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State 
      University Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130, USA.
FAU - Wang, David B
AU  - Wang DB
FAU - Cain, Cooper D
AU  - Cain CD
FAU - Schrott, Lisa M
AU  - Schrott LM
FAU - Ramirez, Julio J
AU  - Ramirez JJ
FAU - King, Michael A
AU  - King MA
FAU - Klein, Ronald L
AU  - Klein RL
LA  - eng
GR  - R01 NS048450/NS/NINDS NIH HHS/United States
GR  - R01 NS048450-04/NS/NINDS NIH HHS/United States
GR  - 48450/PHS HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20111209
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cell Death/genetics
MH  - DNA-Binding Proteins/*biosynthesis/genetics
MH  - Frontotemporal Lobar Degeneration/genetics/*metabolism/pathology
MH  - *Gene Transfer Techniques
MH  - Hippocampus/*metabolism/pathology
MH  - Humans
MH  - Male
MH  - Maze Learning/physiology
MH  - Memory Disorders/genetics/*metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - tau Proteins/*biosynthesis/genetics
PMC - PMC3272160
MID - NIHMS343800
EDAT- 2011/12/20 06:00
MHDA- 2012/03/27 06:00
PMCR- 2013/02/01
CRDT- 2011/12/20 06:00
PHST- 2011/07/15 00:00 [received]
PHST- 2011/11/01 00:00 [revised]
PHST- 2011/12/01 00:00 [accepted]
PHST- 2011/12/20 06:00 [entrez]
PHST- 2011/12/20 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
PHST- 2013/02/01 00:00 [pmc-release]
AID - S0014-4886(11)00453-5 [pii]
AID - 10.1016/j.expneurol.2011.12.002 [doi]
PST - ppublish
SO  - Exp Neurol. 2012 Feb;233(2):807-14. doi: 10.1016/j.expneurol.2011.12.002. Epub 
      2011 Dec 9.