Entry, dispersion and differentiation of microglia in the developing central nervous system

Microglial cells within the developing central nervous system (CNS) originate from mesodermic precursors of hematopoietic lineage that enter the nervous parenchyma from the meninges, ventricular space and/or blood stream. Once in the nervous parenchyma, microglial cells increase in number and disperse throughout the CNS; these cells finally differentiate to become fully ramified microglial cells. In this article we review present knowledge on these phases of microglial development and the factors that probably influence them

Microglia and Microglia-Like Cells: Similar but Different

We want to thank all people for fighting in the front line of the COVID-19 pandemic, during which most parts of this article was written. We also acknowledge the task of the reviewers who contributed to improve the quality of this article.Microglia are the tissue-resident macrophages of the central nervous parenchyma. In mammals, microglia are thought to originate from yolk sac precursors and posteriorly maintained through the entire life of the organism. However, the contribution of microglial cells from other sources should also be considered. In addition to “true” or “bonafide” microglia, which are of embryonic origin, the so-called “microglia-like cells” are hematopoietic cells of bone marrow origin that can engraft the mature brain mainly under pathological conditions. These cells implement great parts of the microglial immune phenotype, but they do not completely adopt the “true microglia” features. Because of their pronounced similarity, true microglia and microglia-like cells are usually considered together as one population. In this review, we discuss the origin and development of these two distinct cell types and their differences. We will also review the factors determining the appearance and presence of microglia-like cells, which can vary among species. This knowledge might contribute to the development of therapeutic strategies aiming at microglial cells for the treatment of diseases in which they are involved, for example neurodegenerative disorders like Alzheimer’s and Parkinson’s diseases.University of Granada, Spain, and FEDER-Junta de Andalucía, Spain (grant number A1-CTS-324- UGR18

Muerte celular y migración de precursores microgliales durante el desarrollo de la retina de codorniz

Los objetivos de este trabajo han sido el estudio de los mecanismos de migración y comportamiento migratorio de los precursores microgliales durante la migración tangencial, la proliferación celular durante el proceso de dispersión de los precursores microgliales, la entrada desde el cuerpo ciliar y el patrón de migración de los precursores microgliales en la periferia retiniana y finalmente un análisis de la relación entre la muerte celular y la migración de los precursores microgliales. Se ha demostrado que los precursores microgliales migran tangencialmente sobre los pies terminales de las células de Muller con un mecanismo similar al descrito en fibroblastos cultivados. Además durante el proceso de migración los precursores microgliales alternan fases de migración activa con fases de orientación y sufren ciclos de división. Por otro lado se ha demostrado la existencia de una entrada de precursores microgliales desde el cuerpo ciliar a la retina periférica que migran circunferencialmente en el margen de la misma. Finalmente, aunque la apoptosis neural en la CCG y en la CNI coincide cronológicamente con la migración tangencial y radial de los precursores microgliales, la escasa colocalización entre ambos demuestra que la muerte celular no es el estímulo que provoca la entrada y migración de los precursores microgliales en la retinaUniv. de Granada, Departamento de Biología Celular. Leída el 29-05-9

Switching Roles: Beneficial Effects of Adipose Tissue-Derived Mesenchymal Stem Cells on Microglia and Their Implication in Neurodegenerative Diseases

Neurological disorders, including neurodegenerative diseases, are often characterized by neuroinflammation, which is largely driven by microglia, the resident immune cells of the central nervous system (CNS). Under these conditions, microglia are able to secrete neurotoxic substances, provoking neuronal cell death. However, microglia in the healthy brain carry out CNS-supporting functions. This is due to the ability of microglia to acquire different phenotypes that can play a neuroprotective role under physiological conditions or a pro-inflammatory, damaging one during disease. Therefore, therapeutic strategies focus on the downregulation of these neuroinflammatory processes and try to re-activate the neuroprotective features of microglia. Mesenchymal stem cells (MSC) of different origins have been shown to exert such effects, due to their immunomodulatory properties. In recent years, MSC derived from adipose tissue have been made the center of attention because of their easy availability and extraction methods. These cells induce a neuroprotective phenotype in microglia and downregulate neuroinflammation, resulting in an improvement of clinical symptoms in a variety of animal models for neurological pathologies, e.g., Alzheimer’s disease, traumatic brain injury and ischemic stroke. In this review, we will discuss the application of adipose tissue-derived MSC and their conditioned medium, including extracellular vesicles, in neurological disorders, their beneficial effect on microglia and the signaling pathways involved