Dissociation of blood-brain barrier disruption and disease manifestation in an aquaporin-4-deficient mouse model of amyotrophic lateral sclerosis

Saori Watanabe-Matsumoto, Yasuhiro Moriwaki, Takashi Okuda, Shinji Ohara, Koji Yamanaka, Yoichiro Abe, Masato Yasui, Hidemi Misawa

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Aquaporin-4 (AQP4) is abundantly expressed in the central nervous system and is involved in the water balance in the cellular environment. Previous studies have reported that AQP4 expression is upregulated in rat models of amyotrophic lateral sclerosis (ALS), a fatal disease that affects motor neurons in the brain and spinal cord. In this study, we report that astrocytic AQP4 overexpression is evident during the course of disease in the spinal cord of an ALS mouse model, as well as in tissue from patients with ALS. AQP4 overexpression appears to be specifically associated with ALS because it was not induced by other experimental manipulations that produced acute or chronic gliosis. In order to examine the contribution of AQP4 to ALS disease development, we crossed AQP4 knockout mice with a mouse model of ALS. Significant improvement in blood-brain barrier (BBB) permeability was observed in the AQP4-deficient ALS mouse model. However, the time to disease onset and total lifespan were reduced in the AQP4-deficient ALS mouse model. The contradictory results suggest that changes in AQP4 may be context-dependent and further studies are required to understand the precise contribution of brain water balance in ALS.

Original languageEnglish
JournalNeuroscience Research
DOIs
Publication statusAccepted/In press - 2017 Jan 1

Fingerprint

Aquaporin 4
Amyotrophic Lateral Sclerosis
Blood-Brain Barrier
Motor Neuron Disease
Gliosis
Water
Spinal Cord Diseases
Brain
Knockout Mice
Permeability
Spinal Cord
Central Nervous System

Keywords

  • ALS
  • AQP4
  • Astrocyte
  • Blood-brain barrier
  • Endfeet
  • Gliosis
  • Microvessel
  • Spinal cord

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{fb1873e394fa424386a6c849281a3dc6,
title = "Dissociation of blood-brain barrier disruption and disease manifestation in an aquaporin-4-deficient mouse model of amyotrophic lateral sclerosis",
abstract = "Aquaporin-4 (AQP4) is abundantly expressed in the central nervous system and is involved in the water balance in the cellular environment. Previous studies have reported that AQP4 expression is upregulated in rat models of amyotrophic lateral sclerosis (ALS), a fatal disease that affects motor neurons in the brain and spinal cord. In this study, we report that astrocytic AQP4 overexpression is evident during the course of disease in the spinal cord of an ALS mouse model, as well as in tissue from patients with ALS. AQP4 overexpression appears to be specifically associated with ALS because it was not induced by other experimental manipulations that produced acute or chronic gliosis. In order to examine the contribution of AQP4 to ALS disease development, we crossed AQP4 knockout mice with a mouse model of ALS. Significant improvement in blood-brain barrier (BBB) permeability was observed in the AQP4-deficient ALS mouse model. However, the time to disease onset and total lifespan were reduced in the AQP4-deficient ALS mouse model. The contradictory results suggest that changes in AQP4 may be context-dependent and further studies are required to understand the precise contribution of brain water balance in ALS.",
keywords = "ALS, AQP4, Astrocyte, Blood-brain barrier, Endfeet, Gliosis, Microvessel, Spinal cord",
author = "Saori Watanabe-Matsumoto and Yasuhiro Moriwaki and Takashi Okuda and Shinji Ohara and Koji Yamanaka and Yoichiro Abe and Masato Yasui and Hidemi Misawa",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.neures.2017.11.001",
language = "English",
journal = "Neuroscience Research",
issn = "0168-0102",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Dissociation of blood-brain barrier disruption and disease manifestation in an aquaporin-4-deficient mouse model of amyotrophic lateral sclerosis

AU - Watanabe-Matsumoto, Saori

AU - Moriwaki, Yasuhiro

AU - Okuda, Takashi

AU - Ohara, Shinji

AU - Yamanaka, Koji

AU - Abe, Yoichiro

AU - Yasui, Masato

AU - Misawa, Hidemi

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Aquaporin-4 (AQP4) is abundantly expressed in the central nervous system and is involved in the water balance in the cellular environment. Previous studies have reported that AQP4 expression is upregulated in rat models of amyotrophic lateral sclerosis (ALS), a fatal disease that affects motor neurons in the brain and spinal cord. In this study, we report that astrocytic AQP4 overexpression is evident during the course of disease in the spinal cord of an ALS mouse model, as well as in tissue from patients with ALS. AQP4 overexpression appears to be specifically associated with ALS because it was not induced by other experimental manipulations that produced acute or chronic gliosis. In order to examine the contribution of AQP4 to ALS disease development, we crossed AQP4 knockout mice with a mouse model of ALS. Significant improvement in blood-brain barrier (BBB) permeability was observed in the AQP4-deficient ALS mouse model. However, the time to disease onset and total lifespan were reduced in the AQP4-deficient ALS mouse model. The contradictory results suggest that changes in AQP4 may be context-dependent and further studies are required to understand the precise contribution of brain water balance in ALS.

AB - Aquaporin-4 (AQP4) is abundantly expressed in the central nervous system and is involved in the water balance in the cellular environment. Previous studies have reported that AQP4 expression is upregulated in rat models of amyotrophic lateral sclerosis (ALS), a fatal disease that affects motor neurons in the brain and spinal cord. In this study, we report that astrocytic AQP4 overexpression is evident during the course of disease in the spinal cord of an ALS mouse model, as well as in tissue from patients with ALS. AQP4 overexpression appears to be specifically associated with ALS because it was not induced by other experimental manipulations that produced acute or chronic gliosis. In order to examine the contribution of AQP4 to ALS disease development, we crossed AQP4 knockout mice with a mouse model of ALS. Significant improvement in blood-brain barrier (BBB) permeability was observed in the AQP4-deficient ALS mouse model. However, the time to disease onset and total lifespan were reduced in the AQP4-deficient ALS mouse model. The contradictory results suggest that changes in AQP4 may be context-dependent and further studies are required to understand the precise contribution of brain water balance in ALS.

KW - ALS

KW - AQP4

KW - Astrocyte

KW - Blood-brain barrier

KW - Endfeet

KW - Gliosis

KW - Microvessel

KW - Spinal cord

UR - http://www.scopus.com/inward/record.url?scp=85035135696&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85035135696&partnerID=8YFLogxK

U2 - 10.1016/j.neures.2017.11.001

DO - 10.1016/j.neures.2017.11.001

M3 - Article

C2 - 29154923

AN - SCOPUS:85035135696

JO - Neuroscience Research

JF - Neuroscience Research

SN - 0168-0102

ER -