A5078083717- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Alzheimer's disease research and treatments
- Immune cells in cancer
- Olfactory and Sensory Function Studies
- Neuroscience and Neuropharmacology Research
- Human Rights and Immigration
- Social Sciences and Policies
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- Finance, Taxation, and Governance
- Phagocytosis and Immune Regulation
- Biochemical Analysis and Sensing Techniques
- Genetic Neurodegenerative Diseases
- RNA Research and Splicing
- Adenosine and Purinergic Signaling
- Economic Theory and Policy
- Sleep and Wakefulness Research
- Computational Drug Discovery Methods
- Nuclear Receptors and Signaling
- Employment, Labor, and Gender Studies
- Pluripotent Stem Cells Research
- Anesthesia and Neurotoxicity Research
- Tryptophan and brain disorders
- Ubiquitin and proteasome pathways
Achucarro Basque Center for Neuroscience
2016-2024
Ikerbasque
2016-2024
University of the Basque Country
2016-2024
Universidad de Salamanca
2007-2024
Instituto de Investigación Biomédica de Salamanca
2022-2024
Instituto de Estudios de Ciencias de la Salud de Castilla y León
2007-2024
University of Coimbra
2012-2020
Centro de Neurociências e Biologia Celular
2016
Euskadiko Parke Teknologikoa
2016
Centro de Investigación del Cáncer
2016
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,...
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...
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...
The cognitive reserve is the capacity of brain to maintain normal performance while exposed insults or ageing. Increasing evidences point a role for interaction between inflammatory conditions and status during Alzheimer's disease (AD) progression. production new neurons along adult life can be considered as one components reserve. Interestingly, neurogenesis decreased in mouse models AD following processes. aim this work reveal long-term impact systemic event on memory wild type (WT) triple...
Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by expanded CAG/polyglutamine repeat in the coding region of huntingtin (htt) gene. Although HD classically considered a motor disorder, there now considerable evidence that early cognitive deficits appear patients before onset disturbances. Here we demonstrate impairment long-term spatial and recognition memory heterozygous knock-in mutant mice (HdhQ7/Q111), genetically accurate mouse model....
Histamine is an amine widely known as a peripheral inflammatory mediator and neurotransmitter in the central nervous system. Recently, it has been suggested that histamine acts innate modulator of microglial activity. Herein, we aimed to disclose role phagocytic activity reactive oxygen species (ROS) production explore consequences histamine-induced neuroinflammation dopaminergic (DA) neuronal survival.The effect on phagocytosis was assessed both vitro by using murine N9 cell line primary...
Activity-dependent gene expression mediating changes of synaptic efficacy is important for memory storage, but the mechanisms underlying transcriptional in age-related disorders are poorly understood. In this study, we report that transcription mediated by cAMP-response element binding protein (CREB)-regulated coactivator CRTC1 impaired neurons and brain from an Alzheimer9s disease (AD) transgenic mouse expressing human β-amyloid precursor (APP<sub>Sw,Ind</sub>). Suppression CRTC1-dependent...
Epidemiological studies indicate that intellectual activity prevents or delays the onset of Alzheimer's disease (AD). Similarly, cognitive stimulation using environmental enrichment (EE), which increases adult neurogenesis and functional integration newborn neurons into neural circuits hippocampus, protects against memory decline in transgenic mouse models AD, but mechanisms involved are poorly understood. To study therapeutic benefits AD we examined effects EE hippocampal a model expressing...
Cognitive decline is associated with gene expression changes in the brain, but transcriptional mechanisms underlying memory impairments cognitive disorders, such as Alzheimer's disease (AD), are largely unknown. Here, we aimed to elucidate relevant responsible for early loss AD by examining pathological, behavioral, and transcriptomic control mutant β-amyloid precursor protein (APP Sw,Ind ) transgenic mice during aging. Genome-wide transcriptome analysis using mouse microarrays revealed...
The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe effect type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression CB1R was detected SVZ-derived immature cells (Nestin-positive), neurons astrocytes. Stimulation by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal SVZ cells, as assessed counting number...
Significance Autophagy impairment is a major hallmark of aging, and any intervention that enhances autophagy potential interest to delay aging. However, it was described the hypothalamus brain area with key role on whole-body In present study, we show an endogenous molecule produced by hypothalamus, neuropeptide Y (NPY), stimulates in rodent hypothalamus. Because both hypothalamic NPY levels decrease age, better understanding neuronal regulation may provide new putative therapeutic...
Abstract Alzheimer´s disease (AD) is characterized by a progressive cognitive decline that correlates with the levels of amyloid β-peptide (Aβ) oligomers. Strong evidences connect changes oligodendrocyte function onset neurodegeneration in AD. However, mechanisms controlling responses to Aβ are still elusive. Here, we tested role differentiation, maturation, and survival isolated oligodendrocytes organotypic cerebellar slices. We found peptides specifically induced local translation 18.5-kDa...
Glial cells are essential to understand Alzheimer's disease (AD) progression, given their role in neuroinflammation and neurodegeneration. There is a need for reliable easy manipulate models that allow studying the mechanisms behind neuron glia communication. Currently available such as co-cultures require complex methodologies and/or might not be affordable all laboratories. With this mind, we aimed establish straightforward vitro setting with neurons glial study AD. We generated optimized...
Abstract Adult neurogenesis persists in the hippocampus of most mammal species during postnatal and adult life, including humans, although it declines markedly with age. The mechanisms driving age‐dependent decline hippocampal are yet not fully understood. progressive loss neural stem cells (NSCs) is a main factor, but true neurogenic output depends initially on actual number activated NSCs each given time point. Because fraction remains constant relative to total population, real parallel...
The paired type homeobox 6 (Pax6) transcription factor (TF) regulates multiple aspects of neural stem cell (NSC) and neuron development in the embryonic central nervous system. However, less is known about role Pax6 maintenance differentiation adult NSCs neurogenesis. Using +/Sey(Dey) mouse, we have analyzed how heterozygosis influences self-renewal proliferation olfactory bulb cells (aOBSCs). In addition, assessed its influence on differentiation, neuronal incorporation, death OB, both vivo...
Different neurodegenerative diseases are caused by aberrant elongation of repeated glutamine sequences normally found in particular human proteins. Although the proteins involved ubiquitously distributed tissues, toxicity targets only defined neuronal populations. Changes an expanded polyglutamine protein possibly influenced endogenous cellular mechanisms, which may be harnessed to produce neuroprotection. Here, we show that ataxin-3, spinocerebellar ataxia type 3, also known as...
Cutaneous squamous cell carcinoma (CSCC) is the second most widespread cancer in humans and its incidence rising. These tumours can evolve as diseases of poor prognosis, therefore it important to identify new markers better predict clinical evolution.We aimed expression pattern microRNAs (miRNAs or miRs) at different stages skin progression a panel murine lines. Owing increasing importance miRNAs pathogenesis cancer, we considered possibility that could help define prognosis CSCC evaluate...
Although we are beginning to understand the late stage of neurodegenerative diseases, molecular defects associated with initiation impaired cognition poorly characterized. Here, demonstrate that in adult brain, coxsackievirus and adenovirus receptor (CAR) is located on neuron projections, at presynapse mature neurons, soma immature neurons hippocampus. In a proinflammatory or diseased environment, CAR lost from Strikingly, hippocampi patients early stages late-onset Alzheimer's disease (AD),...