International Journal of Molecular Sciences

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Open AccessEditorial

Special Issue “Aquaporins in Brain Disease”

by Miriam Echevarría and Pablo García-Miranda

Int. J. Mol. Sci. 2024, 25(6), 3513; https://doi.org/10.3390/ijms25063513 - 20 Mar 2024

Cited by 1 | Viewed by 716

Abstract

Water is an abundant and important component of the human brain, the homeostasis of which is rigorously controlled [...] Full article

(This article belongs to the Special Issue Aquaporins in Brain Disease)

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20 pages, 4771 KiB

Open AccessArticle

Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina

by Laura Carrero, Desireé Antequera, Ignacio Alcalde, Diego Megias, Lara Ordoñez-Gutierrez, Cristina Gutierrez, Jesús Merayo-Lloves, Francisco Wandosell, Cristina Municio and Eva Carro

Int. J. Mol. Sci. 2023, 24(21), 15679; https://doi.org/10.3390/ijms242115679 - 27 Oct 2023

Cited by 2 | Viewed by 1627

Abstract

Alzheimer’s disease (AD), the most prevalent form of dementia, is a neurodegenerative disorder characterized by different pathological symptomatology, including disrupted circadian rhythm. The regulation of circadian rhythm depends on the light information that is projected from the retina to the suprachiasmatic nucleus in [...] Read more.

Alzheimer’s disease (AD), the most prevalent form of dementia, is a neurodegenerative disorder characterized by different pathological symptomatology, including disrupted circadian rhythm. The regulation of circadian rhythm depends on the light information that is projected from the retina to the suprachiasmatic nucleus in the hypothalamus. Studies of AD patients and AD transgenic mice have revealed AD retinal pathology, including amyloid-β (Aβ) accumulation that can directly interfere with the regulation of the circadian cycle. Although the cause of AD pathology is poorly understood, one of the main risk factors for AD is female gender. Here, we found that female APP/PS1 mice at 6- and 12-months old display severe circadian rhythm disturbances and retinal pathological hallmarks, including Aβ deposits in retinal layers. Since brain Aβ transport is facilitated by aquaporin (AQP)4, the expression of AQPs were also explored in APP/PS1 retina to investigate a potential correlation between retinal Aβ deposits and AQPs expression. Important reductions in AQP1, AQP4, and AQP5 were detected in the retinal tissue of these transgenic mice, mainly at 6-months of age. Taken together, our findings suggest that abnormal transport of Aβ, mediated by impaired AQPs expression, contributes to the retinal degeneration in the early stages of AD. Full article

(This article belongs to the Special Issue Aquaporins in Brain Disease)

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15 pages, 4575 KiB

Open AccessArticle

Aquaporin-4 Expression Switches from White to Gray Matter Regions during Postnatal Development of the Central Nervous System

by Francisco Mayo, Lourdes González-Vinceiro, Laura Hiraldo-González, Claudia Calle-Castillejo, Sara Morales-Alvarez, Reposo Ramírez-Lorca and Miriam Echevarría

Int. J. Mol. Sci. 2023, 24(3), 3048; https://doi.org/10.3390/ijms24033048 - 3 Feb 2023

Cited by 8 | Viewed by 3083

Abstract

Aquaporin-4 (AQP4) is the most abundant water channel in the central nervous system and plays a fundamental role in maintaining water homeostasis there. In adult mice, AQP4 is located mainly in ependymal cells, in the endfeet of perivascular astrocytes, and in the glia [...] Read more.

Aquaporin-4 (AQP4) is the most abundant water channel in the central nervous system and plays a fundamental role in maintaining water homeostasis there. In adult mice, AQP4 is located mainly in ependymal cells, in the endfeet of perivascular astrocytes, and in the glia limitans. Meanwhile, its expression, location, and function throughout postnatal development remain largely unknown. Here, the expression of AQP4 mRNA was studied by in situ hybridization and RT-qPCR, and the localization and amount of protein was studied by immunofluorescence and western blotting, both in the brain and spinal cord. For this, wild-type mice of the C57BL/6 line, aged 1, 3, 7, 11, 20, and 60 days, and 18 months were used. The results showed a change in both the expression and location of AQP4 in postnatal development compared to those during adult life. In the early stages of postnatal development it appears in highly myelinated areas, such as the corpus callosum or cerebellum, and as the animal grows, it disappears from these areas, passing through the cortical regions of the forebrain and concentrating around the blood vessels. These findings suggest an unprecedented possible role for AQP4 in the early cell differentiation process, during the first days of life in the newborn animal, which will lead to myelination. Full article

(This article belongs to the Special Issue Aquaporins in Brain Disease)

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14 pages, 7464 KiB

Open AccessArticle

Altered Expression of AQP1 and AQP4 in Brain Barriers and Cerebrospinal Fluid May Affect Cerebral Water Balance during Chronic Hypertension

by Ibrahim González-Marrero, Luis G. Hernández-Abad, Miriam González-Gómez, María Soto-Viera, Emilia M. Carmona-Calero, Leandro Castañeyra-Ruiz and Agustín Castañeyra-Perdomo

Int. J. Mol. Sci. 2022, 23(20), 12277; https://doi.org/10.3390/ijms232012277 - 14 Oct 2022

Cited by 12 | Viewed by 2284

Abstract

Hypertension is the leading cause of cardiovascular affection and premature death worldwide. The spontaneously hypertensive rat (SHR) is the most common animal model of hypertension, which is characterized by secondary ventricular dilation and hydrocephalus. Aquaporin (AQP) 1 and 4 are the main water [...] Read more.

Hypertension is the leading cause of cardiovascular affection and premature death worldwide. The spontaneously hypertensive rat (SHR) is the most common animal model of hypertension, which is characterized by secondary ventricular dilation and hydrocephalus. Aquaporin (AQP) 1 and 4 are the main water channels responsible for the brain’s water balance. The present study focuses on defining the expression of AQPs through the time course of the development of spontaneous chronic hypertension. We performed immunofluorescence and ELISA to examine brain AQPs from 10 SHR, and 10 Wistar–Kyoto (WKY) rats studied at 6 and 12 months old. There was a significant decrease in AQP1 in the choroid plexus of the SHR-12-months group compared with the age-matched control (p < 0.05). In the ependyma, AQP4 was significantly decreased only in the SHR-12-months group compared with the control or SHR-6-months groups (p < 0.05). Per contra, AQP4 increased in astrocytes end-feet of 6 months and 12 months SHR rats (p < 0.05). CSF AQP detection was higher in the SHR-12-months group than in the age-matched control group. CSF findings were confirmed by Western blot. In SHR, ependymal and choroidal AQPs decreased over time, while CSF AQPs levels increased. In turn, astrocytes AQP4 increased in SHR rats. These AQP alterations may underlie hypertensive-dependent ventriculomegaly. Full article

(This article belongs to the Special Issue Aquaporins in Brain Disease)

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Review

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33 pages, 2686 KiB

Open AccessReview

From Homeostasis to Pathology: Decoding the Multifaceted Impact of Aquaporins in the Central Nervous System

by Corneliu Toader, Calin Petru Tataru, Ioan-Alexandru Florian, Razvan-Adrian Covache-Busuioc, David-Ioan Dumitrascu, Luca Andrei Glavan, Horia Petre Costin, Bogdan-Gabriel Bratu and Alexandru Vlad Ciurea

Int. J. Mol. Sci. 2023, 24(18), 14340; https://doi.org/10.3390/ijms241814340 - 20 Sep 2023

Cited by 1 | Viewed by 2772

Abstract

Aquaporins (AQPs), integral membrane proteins facilitating selective water and solute transport across cell membranes, have been the focus of extensive research over the past few decades. Particularly noteworthy is their role in maintaining cellular homeostasis and fluid balance in neural compartments, as dysregulated [...] Read more.

Aquaporins (AQPs), integral membrane proteins facilitating selective water and solute transport across cell membranes, have been the focus of extensive research over the past few decades. Particularly noteworthy is their role in maintaining cellular homeostasis and fluid balance in neural compartments, as dysregulated AQP expression is implicated in various degenerative and acute brain pathologies. This article provides an exhaustive review on the evolutionary history, molecular classification, and physiological relevance of aquaporins, emphasizing their significance in the central nervous system (CNS). The paper journeys through the early studies of water transport to the groundbreaking discovery of Aquaporin 1, charting the molecular intricacies that make AQPs unique. It delves into AQP distribution in mammalian systems, detailing their selective permeability through permeability assays. The article provides an in-depth exploration of AQP4 and AQP1 in the brain, examining their contribution to fluid homeostasis. Furthermore, it elucidates the interplay between AQPs and the glymphatic system, a critical framework for waste clearance and fluid balance in the brain. The dysregulation of AQP-mediated processes in this system hints at a strong association with neurodegenerative disorders such as Parkinson’s Disease, idiopathic normal pressure hydrocephalus, and Alzheimer’s Disease. This relationship is further explored in the context of acute cerebral events such as stroke and autoimmune conditions such as neuromyelitis optica (NMO). Moreover, the article scrutinizes AQPs at the intersection of oncology and neurology, exploring their role in tumorigenesis, cell migration, invasiveness, and angiogenesis. Lastly, the article outlines emerging aquaporin-targeted therapies, offering a glimpse into future directions in combatting CNS malignancies and neurodegenerative diseases. Full article

(This article belongs to the Special Issue Aquaporins in Brain Disease)

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18 pages, 1951 KiB

Open AccessReview

The Role of Aquaporins in Epileptogenesis—A Systematic Review

by Lapo Bonosi, Umberto Emanuele Benigno, Sofia Musso, Kevin Giardina, Rosa Maria Gerardi, Lara Brunasso, Roberta Costanzo, Federica Paolini, Felice Buscemi, Chiara Avallone, Vincenzo Gulino, Domenico Gerardo Iacopino and Rosario Maugeri

Int. J. Mol. Sci. 2023, 24(15), 11923; https://doi.org/10.3390/ijms241511923 - 25 Jul 2023

Cited by 2 | Viewed by 1570

Abstract

Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various physiological and pathological processes in the brain, including water homeostasis, cell migration, and inflammation, among [...] Read more.

Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various physiological and pathological processes in the brain, including water homeostasis, cell migration, and inflammation, among others. Epileptogenesis is a complex and multifactorial process that involves alterations in the structure and function of neuronal networks. Recent evidence suggests that AQPs may also play a role in the pathogenesis of epilepsy. In animal models of epilepsy, AQPs have been shown to be upregulated in regions of the brain that are involved in seizure generation, suggesting that they may contribute to the hyperexcitability of neuronal networks. Moreover, genetic studies have identified mutations in AQP genes associated with an increased risk of developing epilepsy. Our review aims to investigate the role of AQPs in epilepsy and seizure onset from a pathophysiological point of view, pointing out the potential molecular mechanism and their clinical implications. Full article

(This article belongs to the Special Issue Aquaporins in Brain Disease)

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12 pages, 1179 KiB

Open AccessReview

Multifaceted Roles of Aquaporins in the Pathogenesis of Alzheimer’s Disease

by Kaoru Yamada

Int. J. Mol. Sci. 2023, 24(7), 6528; https://doi.org/10.3390/ijms24076528 - 31 Mar 2023

Cited by 10 | Viewed by 3100

Abstract

The central nervous system is highly dependent on water, and disturbances in water homeostasis can have a significant impact on its normal functions. The regulation of water balance is, at least in part, carried out via specialized water channels called aquaporins. In the [...] Read more.

The central nervous system is highly dependent on water, and disturbances in water homeostasis can have a significant impact on its normal functions. The regulation of water balance is, at least in part, carried out via specialized water channels called aquaporins. In the central nervous system, two major aquaporins (AQPs), AQP1 and AQP4, and their potential involvements have been long implicated in the pathophysiology of many brain disorders such as brain edema and Neuromyelitis optica. In addition to these diseases, there is growing attention to the involvement of AQPs in the removal of waste products in Alzheimer’s disease (AD). This indicates that targeting fluid homeostasis is a novel and attractive approach for AD. This review article aims to summarize recent knowledge on the pathological implications of AQPs in AD, discussing unsolved questions and future prospects. Full article

(This article belongs to the Special Issue Aquaporins in Brain Disease)

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10 pages, 1714 KiB

Open AccessReview

AQP4, Astrogenesis, and Hydrocephalus: A New Neurological Perspective

by Leandro Castañeyra-Ruiz, Ibrahim González-Marrero, Luis G. Hernández-Abad, Seunghyun Lee, Agustín Castañeyra-Perdomo and Michael Muhonen

Int. J. Mol. Sci. 2022, 23(18), 10438; https://doi.org/10.3390/ijms231810438 - 9 Sep 2022

Cited by 11 | Viewed by 2639

Abstract

Aquaporin 4 (AQP4) is a cerebral glial marker that labels ependymal cells and astrocytes’ endfeet and is the main water channel responsible for the parenchymal fluid balance. However, in brain development, AQP4 is a marker of glial stem cells and plays a crucial [...] Read more.

Aquaporin 4 (AQP4) is a cerebral glial marker that labels ependymal cells and astrocytes’ endfeet and is the main water channel responsible for the parenchymal fluid balance. However, in brain development, AQP4 is a marker of glial stem cells and plays a crucial role in the pathophysiology of pediatric hydrocephalus. Gliogenesis characterization has been hampered by a lack of biomarkers for precursor and intermediate stages and a deeper understanding of hydrocephalus etiology is needed. This manuscript is a focused review of the current research landscape on AQP4 as a possible biomarker for gliogenesis and its influence in pediatric hydrocephalus, emphasizing reactive astrogliosis. The goal is to understand brain development under hydrocephalic and normal physiologic conditions. Full article

(This article belongs to the Special Issue Aquaporins in Brain Disease)

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