A5073129412- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Immune cells in cancer
- Neuroscience and Neuropharmacology Research
- Estrogen and related hormone effects
- Immune Response and Inflammation
- Phagocytosis and Immune Regulation
- Neurological Disease Mechanisms and Treatments
- Menopause: Health Impacts and Treatments
- Adenosine and Purinergic Signaling
- Autophagy in Disease and Therapy
- Stress Responses and Cortisol
- Hypothalamic control of reproductive hormones
- Fatty Acid Research and Health
- Axon Guidance and Neuronal Signaling
- Multiple Sclerosis Research Studies
- Mitochondrial Function and Pathology
- Neural dynamics and brain function
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Nuclear Receptors and Signaling
- Regulation of Appetite and Obesity
- MicroRNA in disease regulation
- Histone Deacetylase Inhibitors Research
- Extracellular vesicles in disease
University of the Basque Country
2016-2025
Ikerbasque
2016-2025
Achucarro Basque Center for Neuroscience
2016-2025
University Medical Center Hamburg-Eppendorf
2022
Center for Neurosciences
2022
Universität Hamburg
2022
Baylor College of Medicine
2010-2017
Euskadiko Parke Teknologikoa
2014-2016
Texas Children's Hospital
2011-2016
Neurological Research Institute
2011-2016
Abstract Microglia play a critical role in neurodegenerative diseases and the brain aging process. Yet, little is known about functional dynamics of microglia during aging. Thus, using young transgenic mice expressing enhanced‐green fluorescent protein (EGFP) under promoter c‐fms gene for macrophage‐colony stimulating factor receptor, we evaluated vivo ‐induced inflammatory responses EGFP‐expressing sorted by flow cytometry. Aging were characterized presence lipofuscin granules, decreased...
Microglia are the resident brain macrophages and they have been traditionally studied as orchestrators of inflammatory response during infections disease. In addition, microglia has a more benign, less explored role professional phagocytes. Phagocytosis is term coined from Greek to describe receptor-mediated engulfment degradation dead cells microbes. phagocytoses brain-specific cargo, such axonal myelin debris in spinal cord injury or multiple sclerosis, amyloid-β deposits Alzheimer's...
Abstract Steroid hormones such as glucocorticoids and estrogens are well‐known regulators of peripheral immune responses also show anti‐inflammatory properties in the brain. However, expression steroid hormone receptors microglia, pivotal cell that coordinates brain inflammatory response, is still controversial. Here we use real time RT‐PCR to isolated from adult fms ‐EGFP mice by FACS, express glucocorticoid receptor (GR), mineralocorticoid (MR), estrogen alpha (ERα). GR was most abundant...
During adult hippocampal neurogenesis, most newborn cells undergo apoptosis and are rapidly phagocytosed by resident microglia to prevent the spillover of intracellular contents. Here, we propose that phagocytosis is not merely passive corpse removal but has an active role in maintaining neurogenesis. First, found neurogenesis was disrupted male female mice chronically deficient for two pathways: purinergic receptor P2Y12, tyrosine kinases TAM family Mer kinase (MerTK)/Axl. In contrast,...
The word “glia” was coined in the mid‐19th century and defined as “the nerve glue”. For decades, it assumed to be a uniform matrix, until cell theorists raised “neuron doctrine” which stipulated that nervous tissue composed of individual cells. term “astrocytes” introduced late 19th synonym for glial cells, but Santiago Ramón y Cajal who “third element” distinct from cells (astrocytes) neurons. It not 1919 when Pío del Río‐Hortega, an alumnus School, modern terms we use today, thoroughly...
Phagocytosis is essential to maintain tissue homeostasis in a large number of inflammatory and autoimmune diseases, but its role the diseased brain poorly explored. Recent findings suggest that adult hippocampal neurogenic niche, where excess newborn cells undergo apoptosis physiological conditions, phagocytosis efficiently executed by surveillant, ramified microglia. To test whether microglia are efficient phagocytes as well, we confronted them with series apoptotic challenges discovered...
Abstract In multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia infiltrating macrophages contribute to demyelination as well spontaneous remyelination. Nevertheless, specific roles of versus are unknown. We investigated influence in EAE using colony stimulating factor 1 receptor (CSF-1R) inhibitor, PLX5622, deplete microglial population Ccr2 RFP/+ fms EGFP/+ mice, distinguish blood-derived from microglia. PLX5622 treatment depleted...
Microglial phagocytosis of apoptotic debris prevents buildup damage neighbor neurons and inflammatory responses. Whereas microglia are very competent phagocytes under physiological conditions, we report their dysfunction in mouse preclinical monkey models stroke (macaques marmosets) by transient occlusion the medial cerebral artery (tMCAo). By analyzing recently published bulk single cell RNA sequencing databases, show that was not explained transcriptional changes. In contrast, demonstrate...
Abstract The expression of aromatase, the enzyme that catalyzes biosynthesis estrogens from precursor androgens, is increased in brain after injury, suggesting aromatase may be involved neuroprotection. In present study, effect inactivating has been assessed a model neurodegeneration induced by systemic administration neurotoxins. Domoic acid, at dose not neurotoxic intact male mice, significant neuronal loss hilus hippocampal formation mice with reduced levels substrates as result...
Estrogen receptors are direct regulators of transcription that function by binding to specific DNA sequences in promoters target genes. The two cloned forms estrogen receptors, α and β, expressed the central nervous system different neuronal populations. Astrocytes vitro also reported express receptor α; however, this expression has not been confirmed rat brain vivo. apparent absence glia vivo contrasts with well-known effects hormone on astrocytes areas, including hippocampal formation. In...
We have previously shown that 17-β-estradiol protects neurons in the dentate gyrus from kainic acid-induced death vivo. To analyse whether this effect is mediated through estrogen receptors and cross-talk between steroid insulin-like growth factor (IGF) systems, we concomitantly administered antagonists of receptor (ICI 182,780) or IGF-I (JB1) with estradiol. In addition, also without antagonist. JB1 (20 μg/ml), ICI 182,780 (10-7 M), (100 μg/ml) were delivered into left lateral ventricle...
Omega-3 fatty acids (n-3 PUFAs) are essential for the functional maturation of brain. Westernization dietary habits in both developed and developing countries is accompanied by a progressive reduction intake n-3 PUFAs. Low maternal PUFAs has been linked to neurodevelopmental diseases Humans. However, deficiency-mediated mechanisms affecting development central nervous system poorly understood. Active microglial engulfment synapses regulates brain development. Impaired synaptic pruning...