PMID- 36286494
OWN - NLM
STAT- MEDLINE
DCOM- 20221222
LR  - 20230209
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 71
IP  - 2
DP  - 2023 Feb
TI  - Gliovascular interface abnormality in mice with endothelial cell senescence.
PG  - 467-479
LID - 10.1002/glia.24287 [doi]
AB  - In the brain, neurons, glial cells, vascular endothelial cells (ECs), and mural 
      cells form a functional structure referred to as the neurovascular unit (NVU). 
      The functions of the NVU become impaired with aging. To gain insight into the 
      mechanism underlying the aging-related changes in the NVU, we characterized in 
      the present study the gliovascular interface in transgenic mice expressing a 
      dominant-negative form of the telomeric repeat-binding factor 2 (TERF2) 
      specifically in ECs using the Tie2 promoter. In these transgenic mice, senescence 
      occurred in the cerebral ECs and was accompanied by upregulation of the mRNAs of 
      proinflammatory cell adhesion molecules and cytokines. It is noteworthy that in 
      the deep layers of the cerebral cortex, astrocytes exhibited an increase in the 
      signals for S100beta as well as a decrease in the polarization of the water channel 
      aquaporin-4 (AQP4) to the perivascular endfeet of the astrocytes. 
      Mechanistically, the perivascular localization of dystroglycan and its ligand, 
      laminin alpha2, was decreased, and their localization correlated well with the 
      perivascular localization of AQP4, which supports the notion that their 
      interaction regulates the perivascular localization of AQP4. The diminished 
      perivascular localization of laminin alpha2 may be attributed to its proteolytic 
      degradation by the matrix metalloproteinase-2 released by senescent ECs. Pericyte 
      coverage was increased and negatively correlated with the decrease in the 
      perivascular localization of AQP4. We propose that aging-related changes in ECs 
      induce a mild morphological alteration of astrocytes and affect the localization 
      of AQP4 at the gliovascular interface.
CI  - (c) 2022 Wiley Periodicals LLC.
FAU - Kawauchi, Shoji
AU  - Kawauchi S
AD  - Comprehensive Education and Research Center, Kobe Pharmaceutical University, 
      Kobe, Japan.
FAU - Mizoguchi, Taiji
AU  - Mizoguchi T
AD  - Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe, Japan.
FAU - Horibe, Sayo
AU  - Horibe S
AD  - Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe, Japan.
FAU - Tanaka, Toru
AU  - Tanaka T
AD  - Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe, Japan.
FAU - Sasaki, Naoto
AU  - Sasaki N
AD  - Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe, Japan.
FAU - Ikeda, Koji
AU  - Ikeda K
AD  - Laboratory of Clinical Pharmaceutical Science, Kobe Pharmaceutical University, 
      Kobe, Japan.
FAU - Emoto, Noriaki
AU  - Emoto N
AUID- ORCID: 0000-0001-6673-2616
AD  - Laboratory of Clinical Pharmaceutical Science, Kobe Pharmaceutical University, 
      Kobe, Japan.
FAU - Hirata, Ken-Ichi
AU  - Hirata KI
AD  - Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe 
      University Graduate School of Medicine, Kobe, Japan.
FAU - Rikitake, Yoshiyuki
AU  - Rikitake Y
AUID- ORCID: 0000-0001-7207-4656
AD  - Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221026
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Aquaporin 4)
RN  - 0 (Laminin)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Aquaporin 4/genetics/metabolism
MH  - Astrocytes/metabolism
MH  - *Endothelial Cells/metabolism
MH  - *Laminin/metabolism
MH  - *Matrix Metalloproteinase 2/metabolism
MH  - Mice, Transgenic
MH  - *Cellular Senescence
MH  - *Neuroglia/metabolism
OTO - NOTNLM
OT  - aquaporin-4
OT  - astrocyte
OT  - endothelial cell senescence
OT  - laminin
OT  - pericyte
EDAT- 2022/10/27 06:00
MHDA- 2022/12/20 06:00
CRDT- 2022/10/26 09:04
PHST- 2022/10/06 00:00 [revised]
PHST- 2022/05/01 00:00 [received]
PHST- 2022/10/10 00:00 [accepted]
PHST- 2022/10/27 06:00 [pubmed]
PHST- 2022/12/20 06:00 [medline]
PHST- 2022/10/26 09:04 [entrez]
AID - 10.1002/glia.24287 [doi]
PST - ppublish
SO  - Glia. 2023 Feb;71(2):467-479. doi: 10.1002/glia.24287. Epub 2022 Oct 26.