Amanda Sierra

Amanda Sierra
Universidad del País Vasco / Euskal Herriko Unibertsitatea | UPV/EHU · Achucarro Basque Center for Neuroscience

PhD

About

84
Publications
38,349
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8,500
Citations
Citations since 2017
38 Research Items
5301 Citations
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201720182019202020212022202302004006008001,0001,200
201720182019202020212022202302004006008001,0001,200

Publications

Publications (84)
Article
Full-text available
In multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated the influence of microglia in EAE using the colony s...
Article
Microglial phagocytosis of apoptotic debris prevents buildup damage of neighbor neurons and inflammatory responses. Whereas microglia are very competent phagocytes under physiological conditions, we report their dysfunction in mouse and preclinical monkey models of stroke (macaques and marmosets) by transient occlusion of the medial cerebral artery...
Article
Microglial research has advanced considerably in recent decades yet has been constrained by a rolling series of dichotomies such as “resting versus activated” and “M1 versus M2.” This dualistic classification of good or bad microglia is inconsistent with the wide repertoire of microglial states and functions in development, plasticity, aging, and d...
Preprint
Full-text available
In multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated the influence of microglia in EAE using the colony s...
Preprint
In multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated the influence of microglia in EAE using the colony s...
Article
Maternal intake of omega-3 (n-3 PUFAs) and omega-6 (n-6 PUFAs) polyunsaturated fatty acids impacts hippocampal neurogenesis during development, an effect that may extend to adulthood by altering adult hippocampal neurogenesis (AHN). The n-3 PUFAs and n-6 PUFAs are precursors of inflammatory regulators that potentially affect AHN and glia. Additiona...
Preprint
Maternal intake of the polyunsaturated fatty acids omega-3 (n-3 PUFA) and omega-6 (n-6 PUFA) impacts hippocampal neurogenesis during development, an effect that may extend to adulthood by altering adult hippocampal neurogenesis (AHN). n-3 PUFA and n-6 PUFA are precursors of inflammatory regulators that potentially affect AHN and glia. Additionally,...
Preprint
Microglial phagocytosis is rapidly emerging as a therapeutic target in neurodegenerative and neurological disorders. An efficient removal of cellular debris is necessary to prevent buildup damage of neighbor neurons and the development of an inflammatory response. As the brain professional phagocytes, microglia are equipped with an array of mechani...
Article
Full-text available
Microglia act as sensors of injury in the brain, favoring its homeostasis. Their activation and polarization toward a proinflammatory phenotype are associated with injury and disease. These processes are linked to a metabolic reprogramming of the cells, characterized by high rates of glycolysis and suppressed oxidative phosphorylation. This metabol...
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Preprint
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
Full-text available
Autophagy is a complex process that encompasses the enclosure of cytoplasmic debris or dysfunctional organelles in membranous vesicles, the autophagosomes, for their elimination in the lysosomes. Autophagy is increasingly recognized as a critical process in macrophages, including microglia, as it finely regulates innate immune functions such as inf...
Preprint
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the PDF can be download freely on pubmed. https://pubmed.ncbi.nlm.nih.gov/33634751/
Cover Page
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Preprint
Full-text available
Microglia act as sensors of injury in the brain, favouring its homeostasis. Their activation and polarization towards a pro-inflammatory phenotype are associated to injury and disease. These processes are linked to a metabolic reprogramming of the cells, characterized by high rates of glycolysis and suppressed oxidative phosphorylation. This metabo...
Article
Full-text available
Omega-3 fatty acids (n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in Humans. However, the n-3 PU...
Preprint
Full-text available
Autophagy is a complex process that encompasses the enclosure of cytoplasmic debris or dysfunctional organelles in membranous vesicles, the autophagosomes, for their elimination in the lysosomes. A gold-standard method to assess its induction is the analysis of the autophagic flux using as a surrogate the expression of the microtubule-associated li...
Article
Full-text available
Objective Microglial phagocytosis of apoptotic cells is an essential component of the brain regenerative response during neurodegeneration. Whereas it is very efficient in physiological conditions, it is impaired in mouse and human mesial temporal lobe epilepsy, and now we extend our studies to a model of progressive myoclonus epilepsy type 1 in mi...
Preprint
Full-text available
Microglial phagocytosis of apoptotic cells is an essential component of the brain regenerative response in neurodegenerative diseases. Phagocytosis is very efficient in physiological conditions, as well as during apoptotic challenge induced by excitotoxicity or inflammation, but is impaired in mouse and human mesial temporal lobe epilepsy (MTLE). H...
Preprint
Full-text available
The SARS-CoV-2 pandemic has evolved far more aggressively in countries lacking a robust testing strategy to identify infected individuals. Given the global demand for fast and reliable diagnosis to determine the carrier individuals, a stock-out scenario for a number of essential reagents/kits used along the diagnostic process has been foreseen by m...
Article
Full-text available
From development to aging and disease, the brain parenchyma is under the constant threat of debris accumulation, in the form of dead cells and protein aggregates. To prevent garbage buildup, the brain is equipped with efficient phagocytes: the microglia. Microglia are similar, but not identical to other tissue macrophages, and in this review, we wi...
Article
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, we found that neurogenesis was disrupted...
Article
Full-text available
The year 2019 marks the 100-year anniversary of the discovery of microglia by Pío del Río-Hortega. We will recount the state of neuroscience research at the beginning of the 20th century and the heated scientific dispute regarding microglial identity. We will then walk through some of the milestones of microglial research in the decades since then....
Preprint
Full-text available
Omega-3 fatty acids (n-3 polyunsaturated fatty acids; n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseas...
Article
Full-text available
Adult neurogenesis persists in the adult hippocampus due to the presence of multipotent neural stem cells (NSCs). Hippocampal neurogenesis is involved in a range of cognitive functions and is tightly regulated by neuronal activity. NSCs respond promptly to physiological and pathological stimuli altering their neurogenic and gliogenic potential. In...
Preprint
During adult hippocampal neurogenesis, the majority of newborn cells undergo apoptosis and are rapidly phagocytosed by resident microglia to prevent the spillover of their intracellular contents. Here, we propose that phagocytosis is not merely a passive process of corpse removal but has an active role in maintaining adult hippocampal neurogenesis....
Article
Full-text available
New neurons are continuously generated from stem cells and integrated into the adult hippocampal circuitry, contributing to memory function. Several environmental, cellular, and molecular factors regulate the formation of new neurons, but the mechanisms that govern their incorporation into memory circuits are less explored. Herein we will focus on...
Article
Apoptosis is a ubiquitous process occurring in the brain under both physiological and pathological conditions. The central nervous system (CNS) requires an active and efficient clean‐up system to prevent the spillover of intracellular contents into the surrounding parenchyma and suppress the initiation of inflammatory and immune responses. Microgli...
Article
Microglia, the immune cells of the central nervous system, continuously survey the brain to detect alterations and maintain tissue homeostasis. The motility of microglial processes is indicative of their surveying capacity in normal and pathological conditions. The gold standard technique to study motility involves the use of two-photon microscopy...
Article
Full-text available
Adult hippocampal neuroprogenitors give rise to both neurons and astrocytes. As neuroprogenitors are lost with increased age, neurogenesis concomitantly decreases. However, the dynamics of neuron and astrocyte generation throughout adulthood has not been systematically examined. Here, we analyzed the hippocampal niche both longitudinally (from 2 h...
Article
Full-text available
Microglia and non-parenchymal macrophages located in the perivascular space, the meninges and the choroid plexus are independent immune populations that play vital roles in brain development, homeostasis, and tissue healing. Resident macrophages account for a significant proportion of cells in the brain and their density remains stable throughout t...
Article
Full-text available
Background Adult hippocampal neurogenesis, the process of formation of new neurons, occurs throughout life in the hippocampus. New neurons have been associated with learning and memory as well as mood control, and impaired neurogenesis has been linked to depression, schizophrenia, autism and cognitive decline during aging. Thus, understanding the b...
Article
Full-text available
Autophagy is emerging as a core regulator of Central Nervous System (CNS) aging and neurodegeneration. In the brain, it has mostly been studied in neurons, where the delivery of toxic molecules and organelles to the lysosome by autophagy is crucial for neuronal health and survival. However, we propose that the (dys)regulation of autophagy in microg...
Article
Full-text available
Lack of scientific reproducibility is a growing concern and weak experimental practices may contribute to irreproducibility. Here, we describe an optimized and versatile protocol for stereotaxic intrahippocampal administration of Kainic Acid (KA) in mice with a C57Bl6 background. In this protocol, KA administration is combined with in vivo recordin...
Article
Full-text available
Microglia play key roles in brain development, homeostasis, and function, and it is widely assumed that the adult population is long lived and maintained by self-renewal. However, the precise temporal and spatial dynamics of the microglial population are unknown. We show in mice and humans that the turnover of microglia is remarkably fast, allowing...
Article
Full-text available
The word “glia” was coined in the mid-19th century and defined as “the nerve glue”. For decades, it was assumed to be a uniform matrix, until cell theorists raised the “neuron doctrine” which stipulated that nervous tissue was composed of individual cells. The term “astrocytes” was introduced in the late 19th century as a synonym for glial cells, b...
Article
Apoptosis is a widespread phenomenon that occurs in the brain in both physiological and pathological conditions. Dead cells must be quickly removed to avoid the further toxic effects they exert in the parenchyma, a process executed by microglia, the brain professional phagocytes. Although phagocytosis is critical to maintain tissue homeostasis, it...
Article
Full-text available
Phagocytosis is essential to maintain tissue homeostasis in a large number of inflammatory and autoimmune diseases, but its role in the diseased brain is poorly explored. Recent findings suggest that in the adult hippocampal neurogenic niche, where the excess of newborn cells undergo apoptosis in physiological conditions, phagocytosis is efficientl...
Article
Full-text available
Phagocytosis is essential to maintain tissue homeostasis in a large number of inflammatory and autoimmune diseases, but its role in the diseased brain is poorly explored. Recent findings suggest that in the adult hippocampal neurogenic niche, where the excess of newborn cells undergo apoptosis in physiological conditions, phagocytosis is efficientl...
Article
Full-text available
Lifestyle modulates brain function. Diet, stress levels, and physical exercise among other factors influence the “brain cognitive reserve”, that is, the capacity of the brain to maintain a normal function when confronting neurodegenerative diseases, injury, and/or aging. This cognitive reserve relays on several cellular and molecular elements that...
Article
Full-text available
Brain Functional Connectivity (FC) quantifies statistical dependencies between areas of the brain. FC has been widely used to address altered function of brain circuits in control conditions compared to different pathological states, including epilepsy, a major neurological disorder. However, FC also has the as yet unexplored potential to help us u...
Article
Full-text available
Brain Functional Connectivity (FC) quantifies statistical dependencies between areas of the brain. FC has been widely used to address altered function of brain circuits in control conditions compared to different pathological states, including epilepsy, a major neurological disorder. However, FC also has the as yet unexplored potential to help us u...
Article
Adult hippocampal neurogenesis is believed to maintain a range of cognitive functions, many of which decline with age. We recently reported that radial neural stem cells (rNSCs) in the hippocampus undergo activation-dependent conversion into astrocytes, a mechanism that over time contributes to a reduction in the rNSC population. Here, we injected...
Article
Under the guidance of Ramón y Cajal, a plethora of students flourished and began to apply his silver impregnation methods to study brain cells other than neurons: the neuroglia. In the first decades of the XXth century, Nicolás Achúcarro was one of the first researchers to visualize the brain cells with phagocytic capacity that we know today as mic...
Chapter
Full-text available
Microglia are taking a central role in the Neuroscience arena nowadays, following a series of recent discoveries challenging their traditional portrayal as simple “brain macrophages”. Indeed, microglia have unique properties compared with other cells of the immune system, including their origin from the embryonic yolk sac, their capacity for self-r...
Chapter
Full-text available
An emerging view in Neuroscience is that cognitive functions such as learning and memory engage all the various cell types making-up the brain, including surveillant microglia, the resident immune cells. These complex functions prominently depend on the structural remodeling of neuronal circuits, rooted in the formation, strengthening, and eliminat...
Article
An emerging view in Neuroscience is that cognitive functions such as learning and memory engage all the various cell types making-up the brain, including surveillant microglia, the resident immune cells. These complex functions prominently depend on the structural remodeling of neuronal circuits, rooted in the formation, strengthening, and eliminat...
Article
Full-text available
Microglia cells are the major orchestrator of the brain inflammatory response. As such, they are traditionally studied in various contexts of trauma, injury, and disease, where they are well-known for regulating a wide range of physiological processes by their release of proinflammatory cytokines, reactive oxygen species, and trophic factors, among...
Article
The generation of new neurons from neural stem cells (NSCs) throughout adult life in the mammalian brain is a biological process that fascinates scientists for its uniqueness and restorative potential. In the dentate gyrus (DG) of the hippocampus NSCs are able to self-renew and generate new granule cells and astrocytes through a complex and plastic...
Article
Full-text available
Microglia are the resident brain macrophages and they have been traditionally studied as orchestrators of the brain inflammatory response during infections and disease. In addition, microglia has a more benign, less explored role as the brain professional phagocytes. Phagocytosis is a term coined from the Greek to describe the receptor-mediated eng...
Article
Newborn neurons derived from radial glia-like stem cells located in the dentate gyrus integrate into the adult hippocampal circuitry and participate in memory formation, spatial learning, pattern separation, fear conditioning, and anxiety. This process takes place throughout the life span of mammals, including humans; however, it follows a sharp de...
Article
Microglia were recently shown to play unexpected roles in normal brain development and adult physiology. This has begun to dramatically change our view of these resident "immune" cells. Here, we briefly review topics covered in our 2011 Society for Neuroscience minisymposium "The Role of Microglia in the Healthy Brain." This summary is not meant to...
Article
Full-text available
Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is bein...
Article
In the adult hippocampus, neuroprogenitor cells in the subgranular zone (SGZ) of the dentate gyrus give rise to newborn neuroblasts. However, only a small subset of these cells integrates into the hippocampal circuitry as mature neurons at the end of a 4 week period. Here, we show that the majority of the newborn cells undergo death by apoptosis in...
Article
Full-text available
Glucocorticoids are potent regulators of inflammation exerting permissive, stimulatory, and suppressive effects. Glucocorticoid access to intracellular receptors is regulated by the activity of two distinct enzymes known as 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) Type 1 and Type 2, which catalyze the activation or deactivation of glucoco...
Article
Full-text available
Finding biomarkers of human neurological diseases is one of the most pressing goals of modern medicine. Most neurological disorders are recognized too late because of the lack of biomarkers that can identify early pathological processes in the living brain. Late diagnosis leads to late therapy and poor prognosis. Therefore, during the past decade,...
Conference Paper
Background: The ability to diagnose and predict the course of autism is a pressing goal in clinical medicine. However, the specific biomarkers of the disease are unknown, and the diagnosis relies on clinical and neuropsychological criteria. It is now evident that the genetic background is not sufficient to produce a specific autistic phenotype, and...
Article
Full-text available
Steroid hormones such as glucocorticoids and estrogens are well-known regulators of peripheral immune responses and also show anti-inflammatory properties in the brain. However, the expression of steroid hormone receptors in microglia, the pivotal immune cell that coordinates the brain inflammatory response, is still controversial. Here we use real...
Article
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In the CNS, steroid hormones play a major role in the maintenance of brain homeostasis and it's response to injury. Since activated microglia are the pivotal immune cell involved in neurodegeneration, we investigated the possibility that microglia provide a discrete source for the metabolism of active steroid hormones. Using RT-PCR, our results sho...
Article
Full-text available
Microglia play a critical role in neurodegenerative diseases and in the brain aging process. Yet, little is known about the functional dynamics of microglia during aging. Thus, using young and aging transgenic mice expressing enhanced-green fluorescent protein (EGFP) under the promoter of the c-fms gene for macrophage-colony stimulating factor rece...
Article
The nervous system synthesizes steroids that regulate the development and function of neurons and glia, and have neuroprotective properties. The first step in steroidogenesis involves the delivery of free cholesterol to the inner mitochondrial membrane where it can be converted into pregnenolone by the enzyme cytochrome P450side chain cleavage. The...
Article
Full-text available
Decreasing levels of gonadal steroids with aging are associated to an increase in cognitive, neurological and psychiatric disturbances. Estradiol is neuroprotective in animal models of neurodegeneration. However, the effects of hormonal replacement therapy on brain function in postmenopausal women are controversial. A possible alternative to hormon...
Article
Full-text available
The nervous system is a well-known target for steroid hormones, as these hormones regulate brain functions that include neuronal survival and differentiation, myelination, neurogenesis, plasticity and repair after injury. Furthermore, the brain is also a steroidogenic tissue because it possesses the enzymes required to metabolize the common precurs...
Article
The enzyme aromatase catalyzes the conversion of testosterone and other C19 steroids to estradiol. Under normal circumstances, the expression of aromatase in the central nervous system of mammals is restricted to neurons. However, the expression of the enzyme is induced in astrocytes in vitro by stressful stimuli. Furthermore, different types of br...
Article
Full-text available
Estradiol, in addition to its participation in neuroendocrine regulation and sexual behavior, has neuroprotective properties. Different types of brain injury induce the expression of the enzyme aromatase in reactive astroglia. This enzyme catalyzes the conversion of testosterone and other C19 steroids to estradiol. Genetic or pharmacological inhibi...