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Article ; Online: Cellular Distribution of Brain Aquaporins and Their Contribution to Cerebrospinal Fluid Homeostasis and Hydrocephalus.

Trillo-Contreras, José Luis / Ramírez-Lorca, Reposo / Villadiego, Javier / Echevarría, Miriam

2022 Volume 12, Issue 4

Abstract: Brain aquaporins facilitate the movement of water between the four water compartments: blood, cerebrospinal fluid, interstitial fluid, and intracellular fluid. This work analyzes the expression of the four most abundant aquaporins (AQPs) (AQP1, AQP4, ... ...

Abstract	Brain aquaporins facilitate the movement of water between the four water compartments: blood, cerebrospinal fluid, interstitial fluid, and intracellular fluid. This work analyzes the expression of the four most abundant aquaporins (AQPs) (AQP1, AQP4, AQP9, and AQP11) in the brains of mice and discuss their contribution to hydrocephalus. We analyzed available data from single-cell RNA sequencing of the central nervous system of mice to describe the expression of aquaporins and compare their distribution with that based on qPCR, western blot, and immunohistochemistry assays. Expression of AQP1 in the apical cell membrane of choroid plexus epithelial cells and of AQP4 in ependymal cells, glia limitans, and astrocyte processes in the pericapillary end foot is consistent with the involvement of both proteins in cerebrospinal fluid homeostasis. The expression of both aquaporins compensates for experimentally induced hydrocephalus in the animals. Recent data demonstrate that hypoxia in aged animals alters AQP4 expression in the choroidal plexus and cortex, increasing the ventricle size and intraventricular pressure. Cerebral distensibility is reduced in parallel with a reduction in cerebrospinal fluid drainage and cognitive deterioration. We propose that aged mice chronically exposed to hypoxia represent an excellent experimental model for studying the pathophysiological characteristics of idiopathic normal pressure hydrocephalus and roles for AQPs in such disease.
MeSH term(s)	Animals ; Aquaporins/genetics ; Brain/metabolism ; Homeostasis ; Hydrocephalus/genetics ; Hypoxia/metabolism ; Water/metabolism
Chemical Substances	Aquaporins ; Water (059QF0KO0R)
Language	English
Publishing date	2022-03-31
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12040530
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Online: La competitividad empresarial: Un aporte al crecimiento económico y al desarrollo sostenible

Becerra Ossa, Jhennys Paola / Torres Lance, María Mónica / Bravo Yepes, Alexander / Ballesteros Herrera, Merjoury / Yepes Benítez, María José / Madera Soto, Alex Junior / García CorraleS, Natalia / Villadiego Lorduy, Jorge Rafael / López Martínez, César / Sanchez Castillo, Javier Ricardo / Giraldo Zuluaga, Conrado / Acosta Gómez, Anyela

2019

Keywords	KJB ; Economics, finance, business & management ; Competitividad ; Empresas ; Economía
Language	Spanish
Size	1 electronic resource (219 pages)
Publisher	Corporación Universitaria Americana
Publishing place	Barranquilla
Document type	Book ; Online
Note	Spanish
HBZ-ID	HT030381367
ISBN	9789585512740 ; 9585512742
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Aquaporin-4 Mediates Permanent Brain Alterations in a Mouse Model of Hypoxia-Aged Hydrocephalus.

Trillo-Contreras, José Luis / Toledo-Aral, Juan José / Villadiego, Javier / Echevarría, Miriam

International journal of molecular sciences

2021 Volume 22, Issue 18

Abstract: Aquaporin-4 (AQP4) is the principal water channel in the brain being expressed in astrocytes and ependymal cells. AQP4 plays an important role in cerebrospinal fluid (CSF) homeostasis, and alterations in its expression have been associated with ... ...

Abstract	Aquaporin-4 (AQP4) is the principal water channel in the brain being expressed in astrocytes and ependymal cells. AQP4 plays an important role in cerebrospinal fluid (CSF) homeostasis, and alterations in its expression have been associated with hydrocephalus. AQP4 contributes to the development of hydrocephalus by hypoxia in aged mice, reproducing such principal characteristics of the disease. Here, we explore whether these alterations associated with the hydrocephalic state are permanent or can be reverted by reexposure to normoxia. Alterations such as ventriculomegaly, elevated intracranial pressure, and cognitive deficits were reversed, whereas deficits in CSF outflow and ventricular distensibility were not recovered, remaining impaired even one month after reestablishment of normoxia. Interestingly, in AQP4
MeSH term(s)	Age Factors ; Animals ; Aquaporin 4/cerebrospinal fluid ; Aquaporin 4/genetics ; Aquaporin 4/metabolism ; Biomarkers ; Brain/metabolism ; Brain/pathology ; Brain/physiopathology ; Disease Models, Animal ; Disease Susceptibility ; Hydrocephalus/diagnosis ; Hydrocephalus/etiology ; Hydrocephalus/metabolism ; Hydrocephalus/pathology ; Hypoxia/genetics ; Hypoxia/metabolism ; Immunohistochemistry ; Magnetic Resonance Imaging ; Mice ; Phenotype
Chemical Substances	Aquaporin 4 ; Biomarkers
Language	English
Publishing date	2021-09-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22189745
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Article ; Online: Cortistatin as a Novel Multimodal Therapy for the Treatment of Parkinson's Disease.

Serrano-Martínez, Ignacio / Pedreño, Marta / Castillo-González, Julia / Ferraz-de-Paula, Viviane / Vargas-Rodríguez, Pablo / Forte-Lago, Irene / Caro, Marta / Campos-Salinas, Jenny / Villadiego, Javier / Peñalver, Pablo / Morales, Juan Carlos / Delgado, Mario / González-Rey, Elena

International journal of molecular sciences

2024 Volume 25, Issue 2

Abstract: Parkinson's disease (PD) is a complex disorder characterized by the impairment of the dopaminergic nigrostriatal system. PD has duplicated its global burden in the last few years, becoming the leading neurological disability worldwide. Therefore, there ... ...

Abstract	Parkinson's disease (PD) is a complex disorder characterized by the impairment of the dopaminergic nigrostriatal system. PD has duplicated its global burden in the last few years, becoming the leading neurological disability worldwide. Therefore, there is an urgent need to develop innovative approaches that target multifactorial underlying causes to potentially prevent or limit disease progression. Accumulating evidence suggests that neuroinflammatory responses may play a pivotal role in the neurodegenerative processes that occur during the development of PD. Cortistatin is a neuropeptide that has shown potent anti-inflammatory and immunoregulatory effects in preclinical models of autoimmune and neuroinflammatory disorders. The goal of this study was to explore the therapeutic potential of cortistatin in a well-established preclinical mouse model of PD induced by acute exposure to the neurotoxin 1-methil-4-phenyl1-1,2,3,6-tetrahydropyridine (MPTP). We observed that treatment with cortistatin mitigated the MPTP-induced loss of dopaminergic neurons in the substantia nigra and their connections to the striatum. Consequently, cortistatin administration improved the locomotor activity of animals intoxicated with MPTP. In addition, cortistatin diminished the presence and activation of glial cells in the affected brain regions of MPTP-treated mice, reduced the production of immune mediators, and promoted the expression of neurotrophic factors in the striatum. In an in vitro model of PD, treatment with cortistatin also demonstrated a reduction in the cell death of dopaminergic neurons that were exposed to the neurotoxin. Taken together, these findings suggest that cortistatin could emerge as a promising new therapeutic agent that combines anti-inflammatory and neuroprotective properties to regulate the progression of PD at multiple levels.
MeSH term(s)	Animals ; Mice ; Parkinson Disease/drug therapy ; Neurotoxins ; Neuropeptides ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use
Chemical Substances	cortistatin ; Neurotoxins ; Neuropeptides ; Anti-Inflammatory Agents
Language	English
Publishing date	2024-01-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25020694
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Article ; Online: Protection and Repair of the Nigrostriatal Pathway with Stem-Cell-Derived Carotid Body Glomus Cell Transplants in Chronic MPTP Parkinsonian Model.

Villadiego, Javier / Muñoz-Manchado, Ana B / Sobrino, Verónica / Bonilla-Henao, Victoria / Suárez-Luna, Nela / Ortega-Sáenz, Patricia / Pardal, Ricardo / López-Barneo, José / Toledo-Aral, Juan J

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: Antiparkinsonian carotid body (CB) cell therapy has been proven to be effective in rodent and nonhuman primate models of Parkinson's disease (PD), exerting trophic protection and restoration of the dopaminergic nigrostriatal pathway. These neurotrophic ... ...

Abstract	Antiparkinsonian carotid body (CB) cell therapy has been proven to be effective in rodent and nonhuman primate models of Parkinson's disease (PD), exerting trophic protection and restoration of the dopaminergic nigrostriatal pathway. These neurotrophic actions are mediated through the release of high levels of glial-cell-line-derived neurotrophic factor (GDNF) by the CB transplant. Pilot clinical trials have also shown that CB autotransplantation can improve motor symptoms in PD patients, although its effectiveness is affected by the scarcity of the grafted tissue. Here, we analyzed the antiparkinsonian efficacy of in vitro-expanded CB dopaminergic glomus cells. Intrastriatal xenografts of rat CB neurospheres were shown to protect nigral neurons from degeneration in a chronic MPTP mouse PD model. In addition, grafts performed at the end of the neurotoxic treatment resulted in the repair of striatal dopaminergic terminals through axonal sprouting. Interestingly, both neuroprotective and reparative effects induced by in vitro-expanded CB cells were similar to those previously reported by the use of CB transplants. This action could be explained because stem-cell-derived CB neurospheres produce similar amounts of GDNF compared to native CB tissue. This study provides the first evidence that in vitro-expanded CB cells could be a clinical option for cell therapy in PD.
MeSH term(s)	Mice ; Rats ; Humans ; Animals ; Glial Cell Line-Derived Neurotrophic Factor/metabolism ; Carotid Body/metabolism ; Parkinson Disease/therapy ; Parkinson Disease/metabolism ; Dopamine/metabolism ; Dopaminergic Neurons/metabolism ; Cell Transplantation ; Substantia Nigra/metabolism ; Disease Models, Animal ; Corpus Striatum/metabolism
Chemical Substances	Glial Cell Line-Derived Neurotrophic Factor ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2023-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24065575
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Article ; Online: Extracellular matrix protein anosmin-1 overexpression alters dopaminergic phenotype in the CNS and the PNS with no pathogenic consequences in a MPTP model of Parkinson's disease.

Villadiego, Javier / García-Swinburn, Roberto / García-González, Diego / Lebrón-Galán, Rafael / Murcia-Belmonte, Verónica / García-Roldán, Ernesto / Suárez-Luna, Nela / Nombela, Cristina / Marchena, Miguel / de Castro, Fernando / Toledo-Aral, Juan José

Brain structure & function

2023 Volume 228, Issue 3-4, Page(s) 907–920

Abstract: The development and survival of dopaminergic neurons are influenced by the fibroblast growth factor (FGF) pathway. Anosmin-1 (A1) is an extracellular matrix protein that acts as a major regulator of this signaling pathway, controlling FGF diffusion, and ... ...

Abstract	The development and survival of dopaminergic neurons are influenced by the fibroblast growth factor (FGF) pathway. Anosmin-1 (A1) is an extracellular matrix protein that acts as a major regulator of this signaling pathway, controlling FGF diffusion, and receptor interaction and shuttling. In particular, previous work showed that A1 overexpression results in more dopaminergic neurons in the olfactory bulb. Prompted by those intriguing results, in this study, we investigated the effects of A1 overexpression on different populations of catecholaminergic neurons in the central (CNS) and the peripheral nervous systems (PNS). We found that A1 overexpression increases the number of dopaminergic substantia nigra pars compacta (SNpc) neurons and alters the striosome/matrix organization of the striatum. Interestingly, these numerical and morphological changes in the nigrostriatal pathway of A1-mice did not confer an altered susceptibility to experimental MPTP-parkinsonism with respect to wild-type controls. Moreover, the study of the effects of A1 overexpression was extended to different dopaminergic tissues associated with the PNS, detecting a significant reduction in the number of dopaminergic chemosensitive carotid body glomus cells in A1-mice. Overall, our work shows that A1 regulates the development and survival of dopaminergic neurons in different nuclei of the mammalian nervous system.
MeSH term(s)	Mice ; Animals ; Parkinson Disease/pathology ; Substantia Nigra/metabolism ; Extracellular Matrix Proteins/metabolism ; Dopamine/metabolism ; Dopaminergic Neurons/metabolism ; Peripheral Nervous System/metabolism ; Peripheral Nervous System/pathology ; Mice, Inbred C57BL ; Mammals
Chemical Substances	Extracellular Matrix Proteins ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2023-03-30
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2273162-3
ISSN	1863-2661 ; 1863-2653
ISSN (online)	1863-2661
ISSN	1863-2653
DOI	10.1007/s00429-023-02631-0
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Article ; Online: Aquaporin-4 Mediates Permanent Brain Alterations in a Mouse Model of Hypoxia-Aged Hydrocephalus

José Luis Trillo-Contreras / Juan José Toledo-Aral / Javier Villadiego / Miriam Echevarría

International Journal of Molecular Sciences, Vol 22, Iss 9745, p

2021 Volume 9745

Abstract	Aquaporin-4 (AQP4) is the principal water channel in the brain being expressed in astrocytes and ependymal cells. AQP4 plays an important role in cerebrospinal fluid (CSF) homeostasis, and alterations in its expression have been associated with hydrocephalus. AQP4 contributes to the development of hydrocephalus by hypoxia in aged mice, reproducing such principal characteristics of the disease. Here, we explore whether these alterations associated with the hydrocephalic state are permanent or can be reverted by reexposure to normoxia. Alterations such as ventriculomegaly, elevated intracranial pressure, and cognitive deficits were reversed, whereas deficits in CSF outflow and ventricular distensibility were not recovered, remaining impaired even one month after reestablishment of normoxia. Interestingly, in AQP4 −/− mice, the impairment in CSF drainage and ventricular distensibility was completely reverted by re-normoxia, indicating that AQP4 has a structural role in the chronification of those alterations. Finally, we show that aged mice subjected to two hypoxic episodes experience permanent ventriculomegaly. These data reveal that repetitive hypoxic events in aged cerebral tissue promote the permanent alterations involved in hydrocephalic pathophysiology, which are dependent on AQP4 expression.
Keywords	AQP4 ; astrocytes ; hypoxia ; hydrocephalus ; cerebrospinal fluid ; cerebral ventricles ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610 ; 616
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Is Carotid Body Infection Responsible for Silent Hypoxemia in COVID-19 Patients?

Villadiego, Javier / Ramírez-Lorca, Reposo / Cala, Fernando / Labandeira-García, José L / Esteban, Mariano / Toledo-Aral, Juan J / López-Barneo, José

Function (Oxford, England)

2020 Volume 2, Issue 1, Page(s) zqaa032

Language	English
Publishing date	2020-11-23
Publishing country	England
Document type	Editorial
ISSN	2633-8823
ISSN (online)	2633-8823
DOI	10.1093/function/zqaa032
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Article: AQP1 and AQP4 Contribution to Cerebrospinal Fluid Homeostasis.

Trillo-Contreras, José Luis / Toledo-Aral, Juan José / Echevarría, Miriam / Villadiego, Javier

Cells

2019 Volume 8, Issue 2

Abstract: Aquaporin 1 (AQP1), expressed in epithelial cells of the choroid plexus, and aquaporin 4 (AQP4) present in ependymal cells and glia limitants have been proposed to play a significant role in cerebrospinal fluid (CSF) production and homeostasis. However, ... ...

Abstract	Aquaporin 1 (AQP1), expressed in epithelial cells of the choroid plexus, and aquaporin 4 (AQP4) present in ependymal cells and glia limitants have been proposed to play a significant role in cerebrospinal fluid (CSF) production and homeostasis. However, the specific contribution of each water channel to these functions remains unknown, being a subject of debate during the last years. Here, we analyzed in detail how AQP1 and AQP4 participate in different aspects of the CSF homeostasis such as the load and drainage of ventricles, and further explored if these proteins play a role in the ventricular compliance. To do that, we carried out records of intraventricular pressure and CSF outflow, and evaluated ventricular volume by magnetic resonance imaging in AQP1
MeSH term(s)	Animals ; Aquaporin 1/cerebrospinal fluid ; Aquaporin 4/cerebrospinal fluid ; Homeostasis ; Magnetic Resonance Imaging ; Male ; Mice, Knockout ; Ventricular Pressure
Chemical Substances	Aquaporin 4 ; Aquaporin 1 (146410-94-8)
Language	English
Publishing date	2019-02-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409
ISSN	2073-4409
DOI	10.3390/cells8020197
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Article: Genetic Characterization of the Factor VIII Gene in a Cohort of Colombian Patients with Severe Hemophilia A with Inhibitors.

Doncel, Samuel Sarmiento / Mosquera, Gina Alejandra Diaz / Pelaez, Ronald Guillermo / Cortes, Javier Mauricio / Rico, Carol Agudelo / Cadavid, Francisco Javier Meza / Plazas, Nelson Ramirez / Amar, Ivan Alfredo Perdomo / Siado, Jorge Enrique Peña / Rey, Fabian Andres Parrado / Montaño, Cesar Alberto / Villadiego, Alexys Maza

Hematology reports

2022 Volume 14, Issue 2, Page(s) 149–154

Abstract: Hemophilia A is an X-linked bleeding disorder caused by mutations in the FVIII gene. Genetic factors have been shown to be a risk factor for the development of inhibitors. We aimed to identify the specific variations of the FVIII gene of patients with ... ...

Abstract	Hemophilia A is an X-linked bleeding disorder caused by mutations in the FVIII gene. Genetic factors have been shown to be a risk factor for the development of inhibitors. We aimed to identify the specific variations of the FVIII gene of patients with hemophilia A with inhibitors and their association with the inhibitor titer. Methods: Cross-sectional descriptive study. We included 12 Colombian patients from a health care provider, "Integral Solutions SD", who underwent analysis of genetic material (DNA), which was reported by the Molecular Hemostasis Laboratory in Bonn, Germany. Results: All of these patients were diagnosed with severe hemophilia A with inhibitors; ages ranged between 6 and 48 years, with a median age of 13.5 years. Molecular analysis showed the inversion of intron 22 in six patients (50.0%), a small duplication in two patients (16.7%), the inversion of intron 1 in one patient (8.3%), a large deletion (8.3%), a nonsense mutation (8.3%) and a splice-site (8.3%), findings similar to those of other studies. A total of 58.3% of the patients presented inversion mutations with a high risk of developing inhibitors A total of 83.3% of the evaluated patients presented null mutations; however the presence of high inhibitor titers was 66.7%. The most frequent mutation was the inversion intron 22. Knowing the type of mutation and its association as a risk factor for generating inhibitors invites us to delve into other outcomes such as residual values of coagulation FVIII as well as its impact on the half-life of the exogenous factor applied in prophylaxis.
Language	English
Publishing date	2022-05-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2586645-X
ISSN	2038-8330 ; 2038-8322
ISSN (online)	2038-8330
ISSN	2038-8322
DOI	10.3390/hematolrep14020022
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