PMID- 27890830
OWN - NLM
STAT- MEDLINE
DCOM- 20170703
LR  - 20190814
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 341
DP  - 2017 Jan 26
TI  - Time-course of glial changes in the hyperhomocysteinemia model of vascular 
      cognitive impairment and dementia (VCID).
PG  - 42-51
LID - S0306-4522(16)30645-5 [pii]
LID - 10.1016/j.neuroscience.2016.11.024 [doi]
AB  - Vascular cognitive impairment and dementia (VCID) is the second leading cause of 
      dementia behind Alzheimer's disease (AD) and is a frequent co-morbidity with AD. 
      Despite its prevalence, little is known about the molecular mechanisms underlying 
      the cognitive dysfunction resulting from cerebrovascular disease. Astrocytic 
      end-feet almost completely surround intraparenchymal blood vessels in the brain 
      and express a variety of channels and markers indicative of their specialized 
      functions in the maintenance of ionic and osmotic homeostasis and gliovascular 
      signaling. These functions are mediated by end-foot enrichment of the aquaporin 4 
      water channel (AQP4), the inward rectifying potassium channel Kir4.1 and the 
      calcium-dependent potassium channel MaxiK. Using our hyperhomocysteinemia (HHcy) 
      model of VCID we examined the time-course of astrocytic end-foot changes along 
      with cognitive and neuroinflammatory outcomes. We found that there were 
      significant astrocytic end-foot disruptions in the HHcy model. AQP4 becomes 
      dislocalized from the end-feet, there is a loss of Kir4.1 and MaxiK protein 
      expression, as well as a loss of the Dp71 protein known to anchor the Kir4.1, 
      MaxiK and AQP4 channels to the end-foot membrane. Neuroinflammation occurs prior 
      to the astrocytic changes, while cognitive impairment continues to decline with 
      the exacerbation of the astrocytic changes. We have previously reported similar 
      astrocytic changes in models of cerebral amyloid angiopathy (CAA) and therefore, 
      we believe astrocytic end-foot disruption could represent a common cellular 
      mechanism of VCID and may be a target for therapeutic development.
CI  - Copyright (c) 2016. Published by Elsevier Ltd.
FAU - Sudduth, Tiffany L
AU  - Sudduth TL
AD  - University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY 40536, USA.
FAU - Weekman, Erica M
AU  - Weekman EM
AD  - University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY 40536, USA; 
      University of Kentucky, Department of Physiology, Lexington, KY 40536, USA.
FAU - Price, Brittani R
AU  - Price BR
AD  - University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY 40536, USA; 
      University of Kentucky, Department of Physiology, Lexington, KY 40536, USA.
FAU - Gooch, Jennifer L
AU  - Gooch JL
AD  - University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY 40536, USA; 
      University of Kentucky, Department of Physiology, Lexington, KY 40536, USA.
FAU - Woolums, Abigail
AU  - Woolums A
AD  - University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY 40536, USA.
FAU - Norris, Christopher M
AU  - Norris CM
AD  - University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY 40536, USA; 
      University of Kentucky, Department of Pharmacology and Nutritional Sciences, 
      Lexington, KY 40536, USA.
FAU - Wilcock, Donna M
AU  - Wilcock DM
AD  - University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY 40536, USA; 
      University of Kentucky, Department of Physiology, Lexington, KY 40536, USA. 
      Electronic address: donna.wilcock@uky.edu.
LA  - eng
GR  - F31 NS092202/NS/NINDS NIH HHS/United States
GR  - R01 AG027297/AG/NIA NIH HHS/United States
GR  - R01 NS079637/NS/NINDS NIH HHS/United States
GR  - R01 NS097722/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20161125
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (CD11b Antigen)
RN  - 0 (Dystrophin)
RN  - 0 (IL1B protein, mouse)
RN  - 0 (Il12a protein, mouse)
RN  - 0 (Interleukin-12 Subunit p35)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Kcnj10 (channel))
RN  - 0 (Large-Conductance Calcium-Activated Potassium Channels)
RN  - 0 (Potassium Channels, Inwardly Rectifying)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (apo-dystrophin 1)
RN  - 0 (interleukin-6, mouse)
SB  - IM
MH  - Animals
MH  - Astrocytes/*immunology/*pathology
MH  - Brain/blood supply/immunology/pathology
MH  - CD11b Antigen/metabolism
MH  - Cerebral Hemorrhage/immunology/pathology
MH  - Cognitive Dysfunction/*immunology/*pathology
MH  - Dementia, Vascular/*immunology/*pathology
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Dystrophin/metabolism
MH  - Gliosis/immunology/pathology
MH  - Hyperhomocysteinemia/immunology/pathology
MH  - Interleukin-12 Subunit p35/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Interleukin-6/metabolism
MH  - Large-Conductance Calcium-Activated Potassium Channels/metabolism
MH  - Maze Learning/physiology
MH  - Mice, Inbred C57BL
MH  - Potassium Channels, Inwardly Rectifying/metabolism
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC5911565
MID - NIHMS959338
OTO - NOTNLM
OT  - astrocyte
OT  - cerebrovascular
OT  - dementia
OT  - microhemorrhage
OT  - neuroinflammation
EDAT- 2016/11/29 06:00
MHDA- 2017/07/04 06:00
PMCR- 2018/04/23
CRDT- 2016/11/29 06:00
PHST- 2016/07/28 00:00 [received]
PHST- 2016/11/10 00:00 [revised]
PHST- 2016/11/17 00:00 [accepted]
PHST- 2016/11/29 06:00 [pubmed]
PHST- 2017/07/04 06:00 [medline]
PHST- 2016/11/29 06:00 [entrez]
PHST- 2018/04/23 00:00 [pmc-release]
AID - S0306-4522(16)30645-5 [pii]
AID - 10.1016/j.neuroscience.2016.11.024 [doi]
PST - ppublish
SO  - Neuroscience. 2017 Jan 26;341:42-51. doi: 10.1016/j.neuroscience.2016.11.024. 
      Epub 2016 Nov 25.