Valero J.,Achucarro Basque Center for Neuroscience |
Valero J.,Ikerbasque |
Paris I.,Achucarro Basque Center for Neuroscience |
Sierra A.,Achucarro Basque Center for Neuroscience |
And 2 more authors.
ACS Chemical Neuroscience | Year: 2016
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 contribute to brain plasticity allowing adaptive responses to cognitive demands, and one of its key components is the hippocampal neurogenic reserve. Hippocampal neural stem cells give rise to new neurons that integrate into the local circuitry and contribute to hippocampal functions such as memory and learning. Importantly, adult hippocampal neurogenesis is well-known to be modulated by the demands of the environment and lifestyle factors. Diet, stress, and physical exercise directly act on neural stem cells and/or their progeny, but, in addition, they may also indirectly affect neurogenesis by acting on microglia. Microglia, the guardians of the brain, rapidly sense changes in the brain milieu, and it has been recently shown that their function is affected by lifestyle factors. However, few studies have analyzed the modulatory effect of microglia on adult neurogenesis in these conditions. Here, we review the current knowledge about the dialogue maintained between microglia and the hippocampal neurogenic cascade. Understanding how the communication between microglia and hippocampal neurogenesis is affected by lifestyle choices is crucial to maintain the brain cognitive reserve and prevent the maladaptive responses that emerge during disease or injury through adulthood and aging. © 2016 American Chemical Society.
Pascual-Brazo J.,Catholic University of Leuven |
Baekelandt V.,Catholic University of Leuven |
Encinas J.M.,Achucarro Basque Center for Neuroscience |
Encinas J.M.,Ikerbasque |
Encinas J.M.,University of the Basque Country
Current Pharmaceutical Design | Year: 2014
Thirteen years have passed since the neurogenic hypothesis of depression was postulated. One of its aspects, that decreased neurogenesis could be causative of the onset of depression has been difficult to prove. Another aspect, the prediction that increasing neurogenesis would not only be supportive but also required to produce clinical results by antidepressants has gathered experimental validation. Thus a question arises: should new antidepressant strategies based solely on increasing neurogenesis be pursued? At the risk of disappointing the audience, we will not provide a straight answer to this question in this review, but we do hope to enlighten the reader regarding what is known about adult hippocampal neurogenesis, the indications and evidence of its involvement in the onset and treatment of depression, and the advances that have been made in the field in recent years. As we will recount here, the main body of support in favor of the neurogenic hypothesis of depression is based more on intimation than actual proof. However the rare examples that provide support are sufficiently robust to justify investment of resources and effort to clarify the issue, even if the involvement of neurogenesis, both in the etiology and the treatment of depression, is only partial and comprises only subtle components of this complex mental disorder. © 2014 Bentham Science Publishers.
Paz N.,Helmholtz Center for Heavy Ion Research |
Felipe-Blanco I.,University Hospital of Araba |
Royo F.,CIC BioGUNE CIBERehd |
Zabala A.,CIC BioGUNE CIBERehd |
And 6 more authors.
Chromosome Research | Year: 2015
Down syndrome is a common birth defect caused by trisomy of chromosome 21. Chromosomes occupy distinct territories in interphase nuclei, and their distribution within the nuclear space is nonrandom. In humans with Down syndrome, two chromosomes 21 frequently localize proximal to one another and distant from the third chromosome. Here, we investigated the nuclear organization of DYRK1A and SOD1, two genes mapping to chromosome 21 that greatly contribute to the pathology. We found that DYRK1A conserves its central positioning between normal and trisomic cells, whereas SOD1 adopts more peripheral distribution in trisomic cells. We also found that the relative position of these genes with respect to each other varies among the different copies of chromosome territories 21 within a cell, and that this distinct distribution is associated with differences in their expression levels. All together, our results may explain, at least in part, the difference in the expression level of these two genes implicated in the pathogenesis of Down syndrome. © 2015, Springer Science+Business Media Dordrecht.
Martin A.,CIC Biomagune |
Szczupak B.,CIC Biomagune |
Gomez-Vallejo V.,CIC Biomagune |
Domercq M.,University of the Basque Country |
And 10 more authors.
Journal of Neuroscience | Year: 2015
PET imaging of nicotinic acetylcholine receptors (nAChRs) could become an effective tool for the diagnosis and therapy evaluation of neurologic diseases. Despite this, the role of nAChRs α4β2 receptors after brain diseases such as cerebral ischemia and its involvement in inflammatory reaction is still largely unknown. To investigate this, we performed in parallel in vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) with 2[18F]-fluoro-A85380 and [11C]PK11195 at 1, 3, 7, 14, 21, and 28 d after middle cerebral artery occlusion (MCAO) in rats. In the ischemic territory, PET with 2[18F]-fluoro-A85380 and [11C]PK11195 showed a progressive binding increase from days 3–7, followed by a progressive decrease from days 14–28 after cerebral ischemia onset. Ex vivo immunohistochemistry for the nicotinic α4β2 receptor and the mitochondrial translocator protein (18 kDa) (TSPO) confirmed the PET findings and demonstrated the overexpression of α4β2 receptors in both microglia/macrophages and astrocytes from days 7–28 after experimental ischemic stroke. Likewise, the role played by α4β2 receptors on neuroinflammation was supported by the increase of [11C]PK11195 binding in ischemic rats treated with the α4β2 antagonist dihydro-β-erythroidine hydrobromide (DHBE) at day 7 after MCAO. Finally, both functional and behavioral testing showed major impaired outcome at day 1 after ischemia onset, followed by a recovery of the sensorimotor function and dexterity from days 21–28 after experimental stroke. Together, these results suggest that the nicotinic α4β2 receptor could have a key role in the inflammatory reaction underlying cerebral ischemia in rats. © 2015 the authors.
Tremblay M.-E.,Laval University |
Lecours C.,Laval University |
Samson L.,Laval University |
Sanchez-Zafra V.,Achucarro Basque Center for Neuroscience |
And 4 more authors.
Frontiers in Neuroanatomy | Year: 2015
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 twentieth century, Nicolás Achúcarro was one of the first researchers to visualize the brain cells with phagocytic capacity that we know today as microglia. Later, his pupil Pío del Río-Hortega developed modifications of Achúcarro’s methods and was able to specifically observe the fine morphological intricacies of microglia. These findings contradicted Cajal’s own views on cells that he thought belonged to the same class as oligodendroglia (the so called “third element” of the nervous system), leading to a long-standing discussion. It was only in 1924 that Río-Hortega’s observations prevailed worldwide, thus recognizing microglia as a unique cell type. This late landing in the Neuroscience arena still has repercussions in the twenty first century, as microglia remain one of the least understood cell populations of the healthy brain. For decades, microglia in normal, physiological conditions in the adult brain were considered to be merely “resting,” and their contribution as “activated” cells to the neuroinflammatory response in pathological conditions mostly detrimental. It was not until microglia were imaged in real time in the intact brain using two-photon in vivo imaging that the extreme motility of their fine processes was revealed. These findings led to a conceptual revolution in the field: “resting” microglia are constantly surveying the brain parenchyma in normal physiological conditions. Today, following Cajal’s school of thought, structural and functional investigations of microglial morphology, dynamics, and relationships with neurons and other glial cells are experiencing a renaissance and we stand at the brink of discovering new roles for these unique immune cells in the healthy brain, an essential step to understand their causal relationship to diseases. © 2015 Tremblay, Lecours, Samson, Sánchez-Zafra and Sierra.