Alterations in AQP4 expression and polarization in the course of motor neuron degeneration in SOD1G93A mice

Dai, Jiaying; Lin, Wen‐Cheng; Zheng, Minying; Liu, Qiang; He, Binhong; Luo, Chuanming; Lu, Xuancheng; Pei, Zhong; Su, Huanxing; Yao, Xiaoli

doi:10.3892/mmr.2017.6786

Cited by 25 publications

(21 citation statements)

References 44 publications

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“…As reported in the literature, in SOD1(G93A) mice, there is a progressive lumbar MN degeneration during the progression of the pathology [36]. This result is also confirmed by our study, which showe 22.9% MN loss at week 15 and 56.2% MN loss at week 19.…”

Section: Discussionsupporting

confidence: 92%

ASC-Exosomes Ameliorate the Disease Progression in SOD1(G93A) Murine Model Underlining Their Potential Therapeutic Use in Human ALS

Bonafede

Turano

Scambi

et al. 2020

IJMS

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motoneurons. To date, there is no effective treatment available. Exosomes are extracellular vesicles that play important roles in intercellular communication, recapitulating the effect of origin cells. In this study, we tested the potential neuroprotective effect of exosomes isolated from adipose-derived stem cells (ASC-exosomes) on the in vivo model most widely used to study ALS, the human SOD1 gene with a G93A mutation (SOD1(G93A)) mouse. Moreover, we compared the effect of two different routes of exosomes administration, intravenous and intranasal. The effect of exosomes administration on disease progression was monitored by motor tests and analysis of lumbar motoneurons and glial cells, neuromuscular junction, and muscle. Our results demonstrated that repeated administration of ASC-exosomes improved the motor performance; protected lumbar motoneurons, the neuromuscular junction, and muscle; and decreased the glial cells activation in treated SOD1(G93A) mice. Moreover, exosomes have the ability to home to lesioned ALS regions of the animal brain. These data contribute by providing additional knowledge for the promising use of ASC-exosomes as a therapy in human ALS.

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Section: Discussionsupporting

confidence: 92%

ASC-Exosomes Ameliorate the Disease Progression in SOD1(G93A) Murine Model Underlining Their Potential Therapeutic Use in Human ALS

Bonafede

Turano

Scambi

et al. 2020

IJMS

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“…Here, we showed that this technique highly replicates the loss of MNs in the ventral horns of the SOD1 G93A spinal cord. Previous studies using classic pathology demonstrated that MN loss starts at the time of symptom onset (90 days), with a 40% reduction in the number of neurons from 80 to 100 days while no significant change occurs before the appearance of clinical manifestations (Dai et al, 2017). Through XPCT, a similar percentage in neuronal loss can be shown at the same time point, confirming the evidence present in the literature.…”

Section: Discussionsupporting

confidence: 84%

X-ray phase contrast tomography for the investigation of amyotrophic lateral sclerosis

Provinciali

Pieroni²,

Bukreeva³

et al. 2020

J Synchrotron Radiat

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons. Pre-clinical studies drive the development of animal models that well mimic ALS disorder and enable both the dissection of disease processes and an early assessment of therapy efficacy. A comprehensive knowledge of neuronal and vascular lesions in the brain and spinal cord is an essential factor to understand the development of the disease. Spatial resolution and bidimensional imaging are important drawbacks limiting current neuroimaging tools, while neuropathology relies on protocols that may alter tissue chemistry and structure. In contrast, recent ex vivo studies in mice demonstrated that X-ray phase-contrast tomography enables study of the 3D distribution of both vasculature and neuronal networks, without sample sectioning or use of staining. Here we present our findings on ex vivo SOD1G93A ALS mice spinal cord at a micrometric scale. An unprecedented direct quantification of neuro-vascular alterations at different stages of the disease is shown.

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“…AQP4, an aquaporin water channel protein, controls homeostasis of the microenvironment in plasma membranes by guiding a Ca 2+ -dependent gating of the water channel [20]. In motor neurons, alterations in AQP4 expression and polarization lead to a widespread pathological condition [33]. In human glioblastomas, levels of AQP4 mRNA and protein are upregulated.…”

Section: Discussionmentioning

confidence: 99%

The Bradykinin-BDKRB1 Axis Regulates Aquaporin 4 Gene Expression and Consequential Migration and Invasion of Malignant Glioblastoma Cells via a Ca2+-MEK1-ERK1/2-NF-κB Mechanism

Sun

Chen

Lin

et al. 2020

Cancers

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Glioblastoma multiforme (GBM) is the most common form of brain tumor and is very aggressive. Rapid migration and invasion of glioblastoma cells are two typical features driving malignance of GBM. Bradykinin functionally prompts calcium influx via activation of bradykinin receptor B1/B2 (BDKRB1/2). In this study, we evaluated the roles of bradykinin in migration and invasion of glioblastoma cells and the possible mechanisms. Expressions of aquaporin 4 (AQP4) mRNA and protein were upregulated in human glioblastomas. Furthermore, exposure of human U87 MG glioblastoma cells to bradykinin specifically increased levels of BDKRB1. Successively, bradykinin stimulated influx of calcium, phosphorylation of MEK1 and extracellular signal-regulated kinase (ERK)1/2, translocation and transactivation of nuclear factor-kappaB (NF-κB), and expressions of AQP4 mRNA and protein. Concomitantly, migration and invasion of human glioblastoma cells were elevated by bradykinin. Knocking-down BDKRB1 concurrently decreased AQP4 mRNA expression and cell migration and invasion. The bradykinin-induced effects were further confirmed in murine GL261 glioblastoma cells. Therefore, bradykinin can induce AQP4 expression and subsequent migration and invasion through BDKRB1-mediated calcium influx and subsequent activation of a MEK1-ERK1/2-NF-κB pathway. The bradykinin-BDKRB1 axis and AQP4 could be precise targets for treating GBM patients.

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Alterations in AQP4 expression and polarization in the course of motor neuron degeneration in SOD1G93A mice

Cited by 25 publications

References 44 publications

ASC-Exosomes Ameliorate the Disease Progression in SOD1(G93A) Murine Model Underlining Their Potential Therapeutic Use in Human ALS

ASC-Exosomes Ameliorate the Disease Progression in SOD1(G93A) Murine Model Underlining Their Potential Therapeutic Use in Human ALS

X-ray phase contrast tomography for the investigation of amyotrophic lateral sclerosis

The Bradykinin-BDKRB1 Axis Regulates Aquaporin 4 Gene Expression and Consequential Migration and Invasion of Malignant Glioblastoma Cells via a Ca2+-MEK1-ERK1/2-NF-κB Mechanism

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