PMID- 29274742
OWN - NLM
STAT- MEDLINE
DCOM- 20190617
LR  - 20211208
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Print)
IS  - 0969-9961 (Linking)
VI  - 111
DP  - 2018 Mar
TI  - Effect of early embryonic deletion of huntingtin from pyramidal neurons on the 
      development and long-term survival of neurons in cerebral cortex and striatum.
PG  - 102-117
LID - S0969-9961(17)30299-1 [pii]
LID - 10.1016/j.nbd.2017.12.015 [doi]
AB  - We evaluated the impact of early embryonic deletion of huntingtin (htt) from 
      pyramidal neurons on cortical development, cortical neuron survival and motor 
      behavior, using a cre-loxP strategy to inactivate the mouse htt gene (Hdh) in 
      emx1-expressing cell lineages. Western blot confirmed substantial htt reduction 
      in cerebral cortex of these Emx-htt(KO) mice, with residual cortical htt in all 
      likelihood restricted to cortical interneurons of the subpallial lineage and/or 
      vascular endothelial cells. Despite the loss of htt early in development, 
      cortical lamination was normal, as revealed by layer-specific markers. Cortical 
      volume and neuron abundance were, however, significantly less than normal, and 
      cortical neurons showed reduced brain-derived neurotrophic factor (BDNF) 
      expression and reduced activation of BDNF signaling pathways. Nonetheless, 
      cortical volume and neuron abundance did not show progressive age-related decline 
      in Emx-htt(KO) mice out to 24months. Although striatal neurochemistry was normal, 
      reductions in striatal volume and neuron abundance were seen in Emx-htt(KO) mice, 
      which were again not progressive. Weight maintenance was normal in Emx-htt(KO) 
      mice, but a slight rotarod deficit and persistent hyperactivity were observed 
      throughout the lifespan. Our results show that embryonic deletion of htt from 
      developing pallium does not substantially alter migration of cortical neurons to 
      their correct laminar destinations, but does yield reduced cortical and striatal 
      size and neuron numbers. The Emx-htt(KO) mice were persistently hyperactive, 
      possibly due to defects in corticostriatal development. Importantly, deletion of 
      htt from cortical pyramidal neurons did not yield age-related progressive 
      cortical or striatal pathology.
CI  - Copyright (c) 2017 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Dragatsis, I
AU  - Dragatsis I
AD  - Department of Physiology, The University of Tennessee Health Science Center, 
      Memphis, TN 38163, United States.
FAU - Dietrich, P
AU  - Dietrich P
AD  - Department of Physiology, The University of Tennessee Health Science Center, 
      Memphis, TN 38163, United States.
FAU - Ren, H
AU  - Ren H
AD  - Department of Anatomy & Neurobiology, The University of Tennessee Health Science 
      Center, Memphis, TN 38163, United States.
FAU - Deng, Y P
AU  - Deng YP
AD  - Department of Anatomy & Neurobiology, The University of Tennessee Health Science 
      Center, Memphis, TN 38163, United States.
FAU - Del Mar, N
AU  - Del Mar N
AD  - Department of Anatomy & Neurobiology, The University of Tennessee Health Science 
      Center, Memphis, TN 38163, United States.
FAU - Wang, H B
AU  - Wang HB
AD  - Department of Anatomy & Neurobiology, The University of Tennessee Health Science 
      Center, Memphis, TN 38163, United States.
FAU - Johnson, I M
AU  - Johnson IM
AD  - Department of Physiology, The University of Tennessee Health Science Center, 
      Memphis, TN 38163, United States.
FAU - Jones, K R
AU  - Jones KR
AD  - Department of Molecular, Cellular, & Developmental Biology, 347 UCB, University 
      of Colorado, Boulder, CO 80309, United States.
FAU - Reiner, A
AU  - Reiner A
AD  - Department of Anatomy & Neurobiology, The University of Tennessee Health Science 
      Center, Memphis, TN 38163, United States; Department of Ophthalmology, The 
      University of Tennessee Health Science Center, Memphis, TN 38163, United States. 
      Electronic address: areiner@uthsc.edu.
LA  - eng
GR  - R01 CA107183/CA/NCI NIH HHS/United States
GR  - R01 NS028721/NS/NINDS NIH HHS/United States
GR  - R21 NS098137/NS/NINDS NIH HHS/United States
GR  - R01 EY014998/EY/NEI NIH HHS/United States
GR  - R56 NS028721/NS/NINDS NIH HHS/United States
GR  - R01 NS057722/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20171221
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Bdnf protein, mouse)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Htt protein, mouse)
RN  - 0 (Huntingtin Protein)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Count
MH  - Cell Survival/physiology
MH  - Cerebral Cortex/*growth & development/*metabolism/pathology
MH  - Corpus Striatum/*growth & development/*metabolism/pathology
MH  - Female
MH  - Huntingtin Protein/*deficiency/genetics
MH  - Male
MH  - Mice, Knockout
MH  - Motor Activity/physiology
MH  - Pyramidal Cells/*metabolism/pathology
PMC - PMC5821111
MID - NIHMS941226
OTO - NOTNLM
OT  - Cortex
OT  - Development
OT  - Huntingtin knockout
OT  - Neuronal survival
OT  - Striatum
EDAT- 2017/12/25 06:00
MHDA- 2019/06/18 06:00
PMCR- 2018/03/01
CRDT- 2017/12/25 06:00
PHST- 2017/03/28 00:00 [received]
PHST- 2017/11/07 00:00 [revised]
PHST- 2017/12/19 00:00 [accepted]
PHST- 2017/12/25 06:00 [pubmed]
PHST- 2019/06/18 06:00 [medline]
PHST- 2017/12/25 06:00 [entrez]
PHST- 2018/03/01 00:00 [pmc-release]
AID - S0969-9961(17)30299-1 [pii]
AID - 10.1016/j.nbd.2017.12.015 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2018 Mar;111:102-117. doi: 10.1016/j.nbd.2017.12.015. Epub 2017 
      Dec 21.