A5035333299- Nerve injury and regeneration
- Parkinson's Disease Mechanisms and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience of respiration and sleep
- Cerebrospinal fluid and hydrocephalus
- Neuroinflammation and Neurodegeneration Mechanisms
- Long-Term Effects of COVID-19
- Neurological disorders and treatments
- Endoplasmic Reticulum Stress and Disease
- Hematopoietic Stem Cell Transplantation
- Peripheral Neuropathies and Disorders
- Heat shock proteins research
- Fetal and Pediatric Neurological Disorders
- Multiple Sclerosis Research Studies
- Neonatal Respiratory Health Research
- Immune Cell Function and Interaction
- Ion Transport and Channel Regulation
- SARS-CoV-2 and COVID-19 Research
- Systemic Lupus Erythematosus Research
- High Altitude and Hypoxia
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Protease and Inhibitor Mechanisms
- Cell death mechanisms and regulation
- Cardiovascular and Diving-Related Complications
- Infectious Encephalopathies and Encephalitis
Hospital Universitario Virgen del Rocío
2015-2024
Universidad de Sevilla
2015-2024
Biomedical Research Networking Center on Neurodegenerative Diseases
2014-2024
Instituto de Biomedicina de Sevilla
2015-2024
Consejo Superior de Investigaciones Científicas
2015-2022
Instituto de Salud Carlos III
2017
Centro de Investigación Biomédica en Red
2011-2013
The Honourable Society of Lincoln's Inn
2010
Cancer Research UK
2010
Carotid body (CB) glomus cells are highly dopaminergic and express the glial cell line derived neurotrophic factor. The intrastriatal grafting of CB aggregates exerts actions on nigrostriatal neurons in animal models Parkinson disease (PD).We conducted a phase I-II clinical study to assess feasibility, long term safety, neurochemical effects autotransplantation patients with PD.Thirteen advanced PD underwent bilateral stereotactic implantation into striatum. They were assessed before surgery...
Abstract Despite the different animal models of Parkinson's disease developed during last years, they still present limitations modelling slow and progressive process neurodegeneration. Here, we undertook a histological, neurochemical behavioural analysis new chronic parkinsonian mouse model generated by subcutaneous administration low doses MPTP (20 mg/kg, 3 times per week) for months, using both young adult aged mice. The ‐induced nigrostriatal neurodegeneration was accompanied decrease in...
Aquaporin 1 (AQP1), expressed in epithelial cells of the choroid plexus, and aquaporin 4 (AQP4) present ependymal glia limitants have been proposed to play a significant role cerebrospinal fluid (CSF) production homeostasis. However, specific contribution each water channel these functions remains unknown, being subject debate during last years. Here, we analyzed detail how AQP1 AQP4 participate different aspects CSF homeostasis such as load drainage ventricles, further explored if proteins...
The autonomic nervous system is a master regulator of homeostatic processes and stress responses. Sympathetic noradrenergic nerve fibers decrease bone mass, but the role cholinergic signaling in has remained largely unknown. Here, we describe that early postnatally, subset sympathetic undergoes an interleukin-6 (IL-6)-induced switch upon contacting bone. A neurotrophic dependency mediated through GDNF-family receptor-α2 (GFRα2) its ligand, neurturin (NRTN), established between bone-embedded...
Key points The carotid body (CB) is a key chemoreceptor organ that mediates the hyperventilatory response to hypoxia, and contributes process of acclimatisation chronic hypoxaemia. Knowledge CB physiology at cellular molecular levels has advanced considerably in recent times thanks studies on lower mammals; however, information humans practically absent. Here we describe properties human cells slice preparations or after enzymatic dispersion. Besides glomus (type I) glia‐like, sustentacular...
Abstract The human Alzheimer’s disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis started near plaques in both AD mouse models and samples. However, endothelial cells express molecular signature of non-productive (NPA) accumulate, plaques, a tip cell marker IB4 reactive vascular anomalies with NOTCH activity. Notably, NPA induction by loss presenilin, whose mutations cause...
Oxidative damage to dopaminergic nigrostriatal (DNS) neurons plays a central role in the pathogenesis of Parkinson's disease (PD). Glucose-6-phosphate dehydrogenase (G6PD) is key cytoprotective enzyme that provides NADPH, major source reducing equivalents cell. Mutations this are most common enzymopathies worldwide. We have studied vivo G6PD overexpressed specifically DNS pathway and show increase activity soma axon terminals neurons, separately from other or glial cells, protects them...
Glial cell line-derived neurotrophic factor (GDNF) exerts a notable protective effect on dopaminergic neurons in rodent and primate models of Parkinson's disease (PD). The clinical applicability this therapy is, however, hampered by the need durable stable GDNF source allowing safe continuous delivery trophic into brain parenchyma. Intrastriatal carotid body (CB) autografting is neuroprotective potentially useful PD. It induces long-term recovery parkinsonian animals through nigrostriatal...
Parkinson’s disease (PD) is a complex disorder characterized by the impairment of dopaminergic nigrostriatal system. PD has duplicated its global burden in last few years, becoming leading neurological disability worldwide. Therefore, there an urgent need to develop innovative approaches that target multifactorial underlying causes potentially prevent or limit progression. Accumulating evidence suggests neuroinflammatory responses may play pivotal role neurodegenerative processes occur...
X-gal staining is a common procedure used in the histochemical monitoring of gene expression by light microscopy. However, this does not permit direct confocal acquisition images, thus preventing identification labelled cells on depth (Z) axis tissue sections and leading sometimes to erroneous conclusions co-localization studies. Here we report technique, based fluorescence emission mathematically-based optical correction, obtain high quality images. This method, combined with...
Abstract Neuroinflammation mediated by chronically activated microglia, largely caused abnormal accumulation of misfolded α‐synuclein (αSyn) protein, is known to contribute the pathophysiology Parkinson's disease (PD). In this work, based on immunomodulatory activities displayed particular heat‐shock proteins (HSPs), we tested a novel vaccination strategy that used combination αSyn and Grp94 (HSPC4 or Gp96) chaperone murine PD model. We two different procedures, first, adoptive transfer...
Synaptic protein α-synuclein (α-SYN) modulates neurotransmission in a complex and poorly understood manner aggregates the cytoplasm of degenerating neurons Parkinson′s disease. Here, we report that α-SYN present dopaminergic nigral afferents is essential for normal cycling maintenance neural stem cells (NSCs) brain subependymal zone adult male female mice. We also show premature senescence NSCs into non-neurogenic astrocytes mice lacking resembles effects fiber degeneration resulting from...
We have investigated the potential role of molecular chaperones as modulators immune response by using α-synuclein (αSyn) an aggregation-prone model protein. first performed in vitro immunoscreening with 21 preselected candidate and selected 2 from this set displaying immunological activity differential profiles, Grp94/Gp96 FKBP4/52. then immunized mice both chaperone/α-synuclein combinations monomeric or oligomeric (MαSyn OαSyn, respectively), we characterized generated each case. found...
Detection of IgG anti-Aquaporin-4 (AQP4) in serum patients with Neuromyelitis optica syndrome disorders (NMOSD) has improved diagnosis these processes and differentiation from Multiple sclerosis (MS). Recent findings also claim that a subgroup NMOSD, negative for IgG-anti-AQP4, present antibodies anti-AQP1 instead. Explore the presence IgG-anti-AQP1 using previously developed cell-based assay (CBA) highly sensitive to IgG-anti-AQP4. Serum 205 diagnosed as NMOSD (8), multiple (94), optic...
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 restoration the dopaminergic nigrostriatal pathway. These neurotrophic actions are mediated through release high levels glial-cell-line-derived factor (GDNF) by CB transplant. Pilot clinical trials have also shown that autotransplantation can improve motor symptoms PD patients, although its effectiveness is affected...
In the nervous system, cell death by apoptosis plays a critical role during normal development and pathological neurodegeneration. Jun N-terminal kinases (JNKs) are essential regulators of neuronal apoptosis. The AP-1 transcription factor c-Jun is phosphorylated at multiple sites within its transactivation domain JNKs, phosphorylation required for JNK-induced neurotoxicity. While importance as mediator apoptotic JNK signaling in neurons firmly established, molecular mechanism underlying...
Aims: A major limiting factor for cell therapy in Parkinson's disease is that the survival of grafted dopaminergic neurons very poor, which may be improved by administration GDNF, carotid body a good source. Materials & methods: Rats with total unilateral denervation were suspension rat neuroblasts or without aggregates from body. At 1, 2 and 3 months after grafting, rats tested cylinder rotometer killed 4 grafting. Results: We observed graft-derived innervation higher received mixed grafts....
Donor derived regulatory T lymphocytes and the JAK1/2 kinase inhibitor ruxolitinib are currently being evaluated as therapeutic options in treatment of chronic graft versus host disease (cGvHD). In this work, we aimed to determine if combined use both agents can exert a synergistic effect GvHD. For purpose, studied combination vitro GvHD mouse model. Our results show that favors ratio thymic cells conventional culture, without affecting suppressive capacity these Treg. The with Treg showed...