Meninxes, líquido cefalorraquídeo e barreira hematoencefálica

Titulación: Grao en Medicina -- Materia: NeuroanatomíaEsta unidade didáctica está dedicada ao estudo dos “Sistemas de protección do sistema nervioso central (meninxes, líquido cefalorraquídeo e barreira hematoencefálica)”. Inclúese dentro da materia obrigatoria de Neuroanatomía, unha materia da rama das Ciencias da Saúde enmarcada no Módulo “Morfoloxía, estrutura e función do corpo humano”, que se imparte no primeiro semestre do segundo curso do Grao en Medicina da Universidade de Santiago de Compostela. A materia está dedicada ao estudo da morfoloxía externa e a estrutura do sistema nervioso central (SNC) e periférico (SNP) humano. A Neuroanatomía atópase interrelacionada con varias materias, especialmente con: Citoloxía e Xenética, Histoloxía humana xeral e especial, Anatomía humana xeral e Anatomía do Aparato Locomotor, Fisioloxía xeral e Embrioloxía Humana do mesmo módulo o bloque formativo (do primeiro curso). Ó longo do todo o temario faranse constantes referencias a conceptos introducidos por tales materias. O estudo de Fisioloxía Médica durante o mesmo cuadrimestre que se imparte neuroanatomía ofrecerá conceptos complementarios útiles para esta materia. Os coñecementos adquiridos nesta materia serán necesarios para unha correcta asimilación dos conceptos, que se ofertan en Anatomía para técnicas de imaxe no segundo cuadrimestre do segundo curso. Ó mesmo tempo, a Anatomía por técnicas de imaxe contribuirá á compresión e consolidación do estudado en Neuroanatomía, e a achegala ó campo da medicina clínica. Unha sólida base no coñecemento da estrutura do sistema nervioso (SN) humano é fundamental para a resolución de calquera desafío neurodiagnóstico por parte do futuro médico. Permitiralle comprender e situar correctamente as súas funcións e recoñecer as súas manifestacións tanto en individuos sans coma en individuos enfermos, podendo facer as correspondentes aplicacións á clínica. Ademais, os contidos que ofrece a Neuroanatomía, son fundamentais para o deseño de modelos de estudo adecuados para a investigación de enfermidades que afectan ó SN e á correcta interpretación de resultados experimentais. Será polo tanto esencial para a formaciónUniversidade de Santiago de Compostela. Servizo de Normalización Lingüístic

Morfoloxía externa do encéfalo e da medula espiñal

Titulación: Grao en Medicina -- Materia: NeuroanatomíaA unidade didáctica «Morfoloxía externa do encéfalo e da medula espiñal» está incluída na materia NEUROANATOMÍA (6 ECTS), que se imparte no segundo curso do Grao en Medicina na Universidade de Santiago de Compostela, ao longo do primeiro semestre. Esta unidade cursarase a continuación do primeiro bloque do programa da materia, unha vez cos alumnos xa teñen una visión xeral e introdutoria da organización do sistema nervioso. Esta unidade didáctica centrarase no estudo da anatomía macroscópica da medula espiñal e dos diferentes compoñentes do encéfalo. Organízase en 4 temas, que están deseñados para ser desenvolvidos en 14 sesións presenciais, 8 sesións de seminarios de 50 min cada unha, e 6 sesións prácticas coa mesma duración.Universidade de Santiago de Compostela. Servizo de Normalización Lingüístic

Effects of Rho Kinase Inhibitors on Grafts of Dopaminergic Cell Precursors in a Rat Model of Parkinson's Disease.

In models of Parkinson’s disease (PD), Rho kinase (ROCK) inhibitors have antiapoptotic and axonstabilizing effects on damaged neurons, decrease the neuroinflammatory response, and protect against dopaminergic neuron death and axonal retraction. ROCK inhibitors have also shown protective effects against apoptosis induced by handling and dissociation of several types of stem cells. However, the effect of ROCK inhibitors on dopaminergic cell grafts has not been investigated. In the present study, treatment of dopaminergic cell suspension with ROCK inhibitors yielded significant decreases in the number of surviving dopaminergic neurons, in the density of graft-derived dopaminergic fibers, and in graft vascularization. Dopaminergic neuron death also markedly increased in primary mesencephalic cultures when the cell suspension was treated with ROCK inhibitors before plating, which suggests that decreased angiogenesis is not the only factor leading to cell death in grafts. Interestingly, treatment of the host 6-hydroxydopamine-lesioned rats with ROCK inhibitors induced a slight, nonsignificant increase in the number of surviving neurons, as well as marked increases in the density of graft-derived dopaminergic fibers and the size of the striatal reinnervated area. The study findings discourage treatment of cell suspensions before grafting. However, treatment of the host induces a marked increase in graft-derived striatal reinnervation. Because ROCK inhibitors have also exerted neuroprotective effects in several models of PD, treatment of the host with ROCK inhibitors, currently used against vascular diseases in clinical practice, before and after grafting may be a useful adjuvant to cell therapy in PDMinisterio de Salud PI12/00798; RD12/0019/0020Ministerio de Economía y Competitividad BFU2012-370

Effects of Rho kinase inhibitors on grafts of dopaminergic cell precursors in a rat model of Parkinson's Disease

In models of Parkinson’s disease (PD), Rho kinase (ROCK) inhibitors have antiapoptotic and axonstabilizing effects on damaged neurons, decrease the neuroinflammatory response, and protect against dopaminergic neuron death and axonal retraction. ROCK inhibitors have also shown protective effects against apoptosis induced by handling and dissociation of several types of stem cells. However, the effect of ROCK inhibitors on dopaminergic cell grafts has not been investigated. In the present study, treatment of dopaminergic cell suspension with ROCK inhibitors yielded significant decreases in the number of surviving dopaminergic neurons, in the density of graft-derived dopaminergic fibers, and in graft vascularization. Dopaminergic neuron death also markedly increased in primary mesencephalic cultures when the cell suspension was treated with ROCK inhibitors before plating, which suggests that decreased angiogenesis is not the only factor leading to cell death in grafts. Interestingly, treatment of the host 6-hydroxydopamine-lesioned rats with ROCK inhibitors induced a slight, nonsignificant increase in the number of surviving neurons, as well as marked increases in the density of graft-derived dopaminergic fibers and the size of the striatal reinnervated area. The study findings discourage treatment of cell suspensions before grafting. However, treatment of the host induces a marked increase in graft-derived striatal reinnervation. Because ROCK inhibitors have also exerted neuroprotective effects in several models of PD, treatment of the host with ROCK inhibitors, currently used against vascular diseases in clinical practice, before and after grafting may be a useful adjuvant to cell therapy in PDThis work was supported by Spanish Ministry of Health (PI12/00798 and RD12/0019/0020) and Spanish Ministry of Economy and Competitiveness (BFU2012-3708)S

Interaction between angiotensin type 1, type 2, and mas receptors to regulate adult neurogenesis in the brain ventricular–subventricular zone

The renin–angiotensin system (RAS), and particularly its angiotensin type-2 receptors (AT2), have been classically involved in processes of cell proliferation and maturation during development. However, the potential role of RAS in adult neurogenesis in the ventricular-subventricular zone (V-SVZ) and its aging-related alterations have not been investigated. In the present study, we analyzed the role of major RAS receptors on neurogenesis in the V-SVZ of adult mice and rats. In mice, we showed that the increase in proliferation of cells in this neurogenic niche was induced by activation of AT2 receptors but depended partially on the AT2-dependent antagonism of AT1 receptor expression, which restricted proliferation. Furthermore, we observed a functional dependence of AT2 receptor actions on Mas receptors. In rats, where the levels of the AT1 relative to those of AT2 receptor are much lower, pharmacological inhibition of the AT1 receptor alone was sufficient in increasing AT2 receptor levels and proliferation in the V-SVZ. Our data revealed that interactions between RAS receptors play a major role in the regulation of V-SVZ neurogenesis, particularly in proliferation, generation of neuroblasts, and migration to the olfactory bulb, both in young and aged brains, and suggest potential beneficial effects of RAS modulators on neurogenesis.This research was funded by Spanish grants from Ministerio de Economía y Competitividad (BFU2015-70523 and SAF2017-86690-R), Instituto de Salud Carlos III (Retic TERCEL RD16/0011/0016, RD16/0011/0017, and CIBERNED), Galician Government (XUGA, ED431C2018/10; ED431G/05), FEDER (Regional European Development Fund), Generalitat Valenciana (Prometeo 2017-030), and Fundación Emilio Botín-Banco SantanderS

Prostaglandin EP2 Receptors Mediate Mesenchymal Stromal Cell-Neuroprotective Effects on Dopaminergic Neurons

Mesenchymal stromal cells (MSCs) have been shown to have useful properties for cell therapy and have been proposed for treatment of neurodegenerative diseases, including Parkinson's disease. However, the mechanisms involved in recovering dopaminergic neurons are not clear. The present study aims to evaluate the pathways and molecules involved in the neuroprotective effect of MSCs. We analyzed the viability of dopaminergic cells from different sources in response to conditioned medium derived from bone marrow MSC (MSC-CM). MSC-CM increased the viability of dopaminergic cells of rat and human origins, having both neuroprotective and neurorescue activities against effects of dopaminergic neurotoxin 6-hydroxydopamine. We found that lipid removal, inhibition of the prostaglandin E2 receptor 2 (EP2), and its signaling pathway were able to block the effects of MSC-CM on a pure population of dopaminergic neurons. Moreover, in primary mesencephalic cultures and hiPSC-derived neurons, inhibition of EP2 signaling caused a reduction in the number of dopaminergic neurons obtained in culture. Taken together, our results demonstrate for the first time the involvement of prostaglandin signaling from MSC in dopaminergic neuron survival through EP2 receptors, and suggest new approaches for treatment of Parkinson's disease.Grant sponsors of this work are Spanish Ministry of Economy and Competitiveness (BFU2015-70523), Spanish Ministry of Health (RD12/0019/0020, RD16/0011/0016, and CIBERNED), Galician Government (XUGA and Centro singular de investigación de Galicia acreditación 2016-2019, ED431G/05), and European Regional Development Fund (ERDF).Peer reviewe

Brain Renin-Angiotensin System and Microglial Polarization: Implications for Aging and Neurodegeneration

Microglia can transform into proinflammatory/classically activated (M1) or anti-inflammatory/alternatively activated (M2) phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory) to M2 (immunoregulatory) phenotype is necessary to counteract brain damage. Several factors involved in microglial polarization have already been identified. However, the effects of the brain renin-angiotensin system (RAS) on microglial polarization are less known. It is well known that there is a “classical” circulating RAS; however, a second RAS (local or tissue RAS) has been observed in many tissues, including brain. The locally formed angiotensin is involved in local pathological changes of these tissues and modulates immune cells, which are equipped with all the components of the RAS. There are also recent data showing that brain RAS plays a major role in microglial polarization. Level of microglial NADPH-oxidase (Nox) activation is a major regulator of the shift between M1/proinflammatory and M2/immunoregulatory microglial phenotypes so that Nox activation promotes the proinflammatory and inhibits the immunoregulatory phenotype. Angiotensin II (Ang II), via its type 1 receptor (AT1), is a major activator of the NADPH-oxidase complex, leading to pro-oxidative and pro-inflammatory effects. However, these effects are counteracted by a RAS opposite arm constituted by Angiotensin II/AT2 receptor signaling and Angiotensin 1–7/Mas receptor (MasR) signaling. In addition, activation of prorenin-renin receptors may contribute to activation of the proinflammatory phenotype. Aged brains showed upregulation of AT1 and downregulation of AT2 receptor expression, which may contribute to a pro-oxidative pro-inflammatory state and the increase in neuron vulnerability. Several recent studies have shown interactions between the brain RAS and different factors involved in microglial polarization, such as estrogens, Rho kinase (ROCK), insulin-like growth factor-1 (IGF-1), tumor necrosis factor α (TNF)-α, iron, peroxisome proliferator-activated receptor gamma, and toll-like receptors (TLRs). Metabolic reprogramming has recently been involved in the regulation of the neuroinflammatory response. Interestingly, we have recently observed a mitochondrial RAS, which is altered in aged brains. In conclusion, dysregulation of brain RAS plays a major role in aging-related changes and neurodegeneration by exacerbation of oxidative stress (OS) and neuroinflammation, which may be attenuated by pharmacological manipulation of RAS components

Dopamine regulates adult neurogenesis in the ventricular-subventricular zone via dopamine D3 angiotensin type 2 receptor interactions

Adult neurogenesis is a dynamic and highly regulated process, and different studies suggest that dopamine modulates ventricular-subventricular zone (V-SVZ) neurogenesis. However, the specific role of dopamine and the mechanisms/factors underlying its effects on physiological and pathological conditions such as Parkinson's disease (PD) are not fully understood. Recent studies have described counter-regulatory interactions between renin-angiotensin system (RAS) and dopamine in peripheral tissues and in the nigrostriatal system. We have previously demonstrated that angiotensin receptors regulate proliferation and generation of neuroblasts in the rodent V-SVZ. However, possible interactions between dopamine receptors and RAS in the V-SVZ and their role in alterations of neurogenesis in animal models of PD have not been investigated. In V-SVZ cultures, activation of dopamine receptors induced changes in the expression of angiotensin receptors. Moreover, dopamine, via D2-like receptors and particularly D3 receptors, increased generation of neurospheres derived from the V-SVZ and this effect was mediated by angiotensin type-2 (AT2) receptors. In rats, we observed a marked reduction in proliferation and generation of neuroblasts in the V-SVZ of dopamine-depleted animals, and inhibition of AT1 receptors or activation of AT2 receptors restored proliferation and generation of neuroblasts to control levels. Moreover, intrastriatal mesencephalic grafts partially restored proliferation and generation of neuroblasts observed in the V-SVZ of dopamine-depleted rats. Our data revealed that dopamine and angiotensin receptor interactions play a major role in the regulation of V-SVZ and suggest potential beneficial effects of RAS modulators on the regulation of adult V-SVZ neurogenesisThis work was supported by grants from Instituto de Salud Carlos III (RD16/011/0016), Secretaría de Estado de Investigación, Desarrollo e Innovación (Grant/Award, number RTI2018-098830-B-I00), Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (ED431G/05, ED431C 2018/10), and European Regional Development Fund (FEDER)S