Pro-Inflammatory Role of AQP4 in Mice Subjected to Intrastriatal Injections of the Parkinsonogenic Toxin MPP+

Prydz, Agnete; Stahl, Katja; Zahl, Soulmaz; Skauli, Nadia; Skare, Øivind; Ottersen, Ole Petter; Amiry-Moghaddam, Mahmood

doi:10.3390/cells9112418

Cited by 14 publications

(14 citation statements)

References 75 publications

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“…Also, the study concluded that the reason for these opposing findings lay in the integrity or otherwise of the BBB in mice. In contrast to the intact BBB in this study, disruption of the BBB can expose neurons and glial cells directly to inflammatory cells and factors ( Prydz et al, 2020 ). The swelling effect in AQP4-induced astrocytes appeared to also be observed in the brain tissue of patients with PD, who show more severe water accumulation in the substantia nigra.…”

Section: Astrocytic Ion Channels In Parkinson’s Diseasementioning

confidence: 84%

“…However, evidence exists that AQP4-mediated astrocyte swelling also has a role in promoting neuroinflammation. Prydz et al (2020) also injected MPP + into the striatum of AQP4-deficient mice. Wild-type mice were found to have more pronounced neuroinflammation than AQP4-KO mice and a deficiency of astrocytic AQP4 channels induced weaker microglia activation than in wild-type mice.…”

Section: Astrocytic Ion Channels In Parkinson’s Diseasementioning

confidence: 99%

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Ion Channel Dysfunction in Astrocytes in Neurodegenerative Diseases

Wang

Shang

et al. 2022

Front. Physiol.

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Astrocytes play an important role in the central nervous system (CNS). Ion channels in these cells not only function in ion transport, and maintain water/ion metabolism homeostasis, but also participate in physiological processes of neurons and glial cells by regulating signaling pathways. Increasing evidence indicates the ion channel proteins of astrocytes, such as aquaporins (AQPs), transient receptor potential (TRP) channels, adenosine triphosphate (ATP)-sensitive potassium (K-ATP) channels, and P2X7 receptors (P2X7R), are strongly associated with oxidative stress, neuroinflammation and characteristic proteins in neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS). Since ion channel protein dysfunction is a significant pathological feature of astrocytes in neurodegenerative diseases, we discuss these critical proteins and their signaling pathways in order to understand the underlying molecular mechanisms, which may yield new therapeutic targets for neurodegenerative disorders.

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Section: Astrocytic Ion Channels In Parkinson’s Diseasementioning

confidence: 84%

Section: Astrocytic Ion Channels In Parkinson’s Diseasementioning

confidence: 99%

Ion Channel Dysfunction in Astrocytes in Neurodegenerative Diseases

Wang

Shang

et al. 2022

Front. Physiol.

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“…Additionally, a model of CCI for post-traumatic epilepsy also indicated that dysregulation of AQP4 leads to neurological deficits, which can be through the swelling of astrocytic endfeet (Szu et al, 2020;Lu et al, 2021). Theories have also found dysregulation of AQP4 to play a pro-inflammatory role contributing to neurological deficits in diseases such as Parkinson's; thus, the role of AQP4 following closed-head impact TBI is important to study (Tamtaji et al, 2019;Prydz et al, 2020). While the experimental design of the compared studies may differ, the similarities in results, with both the present and a compared study showing increases in AQP4 following injury and disease, suggests that the closed-head aspect of this model still produces pathology that is representative of pathology reported in traditional CCI models that replicate pathology observed following mTBI in humans (Yao et al, 2015;Szu et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Regional variances depict a unique glial-specific inflammatory response following closed-head injury

White

VandeVord²

2023

Front. Cell. Neurosci.

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Mild traumatic brain injuries (mTBI) constitute a significant health concern with clinical symptoms ranging from headaches to cognitive deficits. Despite the myriad of symptoms commonly reported following this injury, there is still a lack of knowledge on the various pathophysiological changes that occur. Preclinical studies are at the forefront of discovery delineating the changes that occur within this heterogeneous injury, with the emergence of translational models such as closed-head impact models allowing for further exploration of this injury mechanism. In the current study, male rats were subjected to a closed-head controlled cortical impact (cCCI), producing a concussion (mTBI). The pathological effects of this injury were then evaluated using immunoflourescence seven days following. The results exhibited a unique glial-specific inflammatory response, with both the ipsilateral and contralateral sides of the cortex and hippocampus showing pathological changes following impact. Overall these findings are consistent with glial changes reported following concussions and may contribute to subsequent symptoms.

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“…We have previously shown that deletion of aquaporin-4 (AQP4), the predominant aquaporin in the central nervous system and a water-selective member of the aquaporin family, significantly reduces the inflammatory response to intrastriatal injections of 1-methyl-4-phenylpyridinium (MPP + )—a parkinsonogenic compound that is known to induce a strong inflammatory response [ 9 ]. This finding inspired us to use the same experimental model to explore whether AQP9—similar to AQP4 and analogous to the situation in peripheral tissues—plays a proinflammatory role in the brain.…”

Section: Introductionmentioning

confidence: 99%

Aquaporin-9 in the Brain Inflammatory Response: Evidence from Mice Injected with the Parkinsonogenic Toxin MPP+

et al. 2023

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More than 20 years have passed since the first demonstration of Aquaporin-9 (AQP9) in the brain. Yet its precise localization and function in brain tissue remain unresolved. In peripheral tissues, AQP9 is expressed in leukocytes where it is involved in systemic inflammation processes. In this study, we hypothesized that AQP9 plays a proinflammatory role in the brain, analogous to its role in the periphery. We also explored whether Aqp9 is expressed in microglial cells, which would be supportive of this hypothesis. Our results show that targeted deletion of Aqp9 significantly suppressed the inflammatory response to the parkinsonian toxin 1-methyl-4-phenylpyridinium (MPP+). This toxin induces a strong inflammatory response in brain. After intrastriatal injections of MPP+, the increase in transcript levels of proinflammatory genes was less pronounced in AQP9−/− mice compared with wild-type controls. Further, in isolated cell subsets, validated by flow cytometry we demonstrated that Aqp9 transcripts are expressed in microglial cells, albeit at lower concentrations than in astrocytes. The present analysis provides novel insight into the role of AQP9 in the brain and opens new avenues for research in the field of neuroinflammation and chronic neurodegenerative disease.

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Pro-Inflammatory Role of AQP4 in Mice Subjected to Intrastriatal Injections of the Parkinsonogenic Toxin MPP+

Cited by 14 publications

References 75 publications

Ion Channel Dysfunction in Astrocytes in Neurodegenerative Diseases

Ion Channel Dysfunction in Astrocytes in Neurodegenerative Diseases

Regional variances depict a unique glial-specific inflammatory response following closed-head injury

Aquaporin-9 in the Brain Inflammatory Response: Evidence from Mice Injected with the Parkinsonogenic Toxin MPP+

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