Neuron and Glial Cell Metabolism
Objectives
Students will acquire critical knowledge and concepts related to several aspects of metabolism of brain cells. The main focus will be glial cell metabolism and how these cells support neuronal function. Namely, how microglial metabolism cross-talks with inflammation control and how astrocytes respond to neuronal metabolic needs and/or cerebral blood perfusion. Moreover, implications of glial cell metabolism on human health (development) and disease (stroke or neurodegeneration) will be tackled.
Two levels of learning are expected: (i) theoretical knowledge about the subject and (ii) addressing students to state of the art biomedical research and its methodology.
The aim is to integrate the taught metabolic pathways of glial cells with the underlying mechanisms of brain function under physiological and pathological conditions. Furthermore, students will be taught to read, analyze and critically evaluate scientific papers and will learn the main experimental approaches used in Biomedical research. Being a 3rd year curricular unit, it may support students for their future choices for Master degrees or other specializations.
General characterization
Code
13320
Credits
3.0
Responsible teacher
Helena Luísa de Araújo Vieira
Hours
Weekly - 2
Total - 30
Teaching language
Português
Prerequisites
NA
Bibliography
Review papers
Allaman I, (2011). Trends Neurosci 34, 76–87.
Iadecola C (2017). Neuron 96, 17–42.
Ito K & Suda T (2014). Nat Rev Mol Cell Biol 15, 243–256.
Li Q & Barres BA (2018). Nat Rev Immunol 18, 225–242.
Pellerin L (2012). J Cereb Blood Flow Metab 32, 1152–1166.
Sierra A, (2019). Trends Neurosci 42, 778–792.
Sweeney MD, (2019). Physiol Rev 99, 21–78.
Szepesi Z, (2018). Front Cell Neurosci
Vieira HLA, (2011). Prog Neurobiol 93, 444–455.
Belanger M, (2011) Cell Metab;14:724–38.
Rojo AI, (2014) Antioxid Redox Signal;21:1766–801
Books
Glia
2015
Cold Spring Harbor Laboratory Press
The Glutamate/GABA-Glutamine Cycle: amino acid neurotransmitter homeostasis
Arne Schousbooe and Ursula Sonnewald
Advances in Neurology 13
Springer
Teaching method
The Curricular Unit is divided into three main components:
(i) Theoretical Classes – Presentation of the program content by the teacher, focusing on the fundamental concepts of cerebral metabolism and its cells. The bibliography will primarily consist of textbooks and review articles. The methodology will involve content delivery using PowerPoint slide presentations.
(ii) Seminars – A deeper and research-oriented approach will be provided through seminars conducted by the instructor or invited scientists. The bibliography will be based on review articles and original research papers. The seminars aim to raise scientific questions on specific topics while aiding and enhancing students’ preparation for journal clubs.
(iii) Presentation and Discussion of Scientific Articles (Journal Clubs) – Students will learn part of the material through literature research, allowing them to engage with the state of the art in a specific scientific topic. The goal is to make students more independent in searching for and selecting information, particularly in selecting scientific sources, reading scientific articles, and extracting relevant information. Students will be encouraged to understand and integrate the various contents covered in theoretical classes and seminars, contributing to the consolidation of knowledge and the development of a critical scientific mindset.
Evaluation method
The evaluation of students will have 3 components:
50% for the theoretical component consisting of one test throughout the semester,
45% for the practical component (through the presentation of scientific articles and group work),
5% for participation in classes.
There is minimum grade for the test: 9.5 points out of 20
Subject matter
Syllabus is organized in 6 different subjects related to metabolism of brain cells, starting from a brief introduction about neurons up to subjects related to human health and disease. Students will acquire and learn how to apply, in a research context, basic concepts on the following subjects:
1) Neuronal metabolism
Students have already acquired the needed knowledge about Central Nervous System (CNS) and neurons at Physiology curricular unit. Thus, these topics will be briefly mentioned, with a particular focus on action potential because of neuronal energetic needs. Then, neuronal metabolism will be studied, namely the different carbon sources used by neurons and their main dependence on oxygen. Likewise, the importance of neuronal anti-oxidant machinery will also be approached.
2) Astrocytes: characteristics, function, metabolism and cross-talk with neurons
Astrocytes are the most abundant glial cells, and their morphology, characteristics and metabolism will be taught. Most importantly, the astrocyte-neuron interaction will be approached at different levels: glutamine-glutamate cycle; astrocyte-neuron lactate shuttle, amino acid recycling, pH buffering and glutathione metabolism
3) Blood Brain Barrier (BBB), Neurovascular Unit and the control of brain metabolic needs
BBB will be described in terms of main cell types composition and function (astrocytes, endothelial cells and pericytes), as well as how other cell types (vessel smooth muscle cells and microglia) can also control BBB function. The concept of neurovascular unit will be taught and how this unit controls brain metabolism, connecting the cerebral metabolic needs to blood perfusion. The neuroprotective functions of BBB will also be tackled, namely the prevention of blood cells, neurotoxic factors and pathogens from entering into the brain parenchyma. Cell-to-cell adhesions structures, such as tight junction and adherent junction belt proteins will also be explained.
4) Microglia, inflammation and metabolism
The concept that microglia are the “brain immune resident cells” will be taught. Microglial control of neuroinflammation and phagocytosis are the main functions that will be presented. The anti- and proinflammatory state of microglia will be studied at different levels: morphology, production and release of different cytokines (and their signaling) and microglial metabolism. Metabolic shifts between oxidative and glycolytic pathways regulate the neuroinflammatory response of microglia, which will be approached during the course. For example, it will be studied how glycolytic metabolites are involved in the stimulation of pro-inflammatory features of microglia. In addition, the molecular mechanisms underlying the bidirectional microglia-.neuron communication will also be explained.
5) Neurogenesis and cell metabolism
Introduction of adult neurogenesis will be presented. Then, the role of cell metabolism in the control of neuronal differentiation will be discussed. In particular how the metabolic shift from glycolytic to oxidative pathways modulates the switch from proliferative state of stem cells into differentiated cells.
6) Glial cell metabolism and Diseases
Ischemic brain diseases
Ischemic stroke and newborn hypoxic ischemic encephalopathy are two examples of cerebral ischemic pathologies tightly related to brain metabolism regulation. None or low blood perfusion leads to ischemic lesions due to the lack of oxygen and carbon source (mainly glucose) supply. These lesions are associated with metabolic defaults leading to excitotoxicity, oxidative stress, inflammation, cell death, among other deleterious processes. These concepts and facts will be taught and discussed with students, along with the potential therapeutic strategies to prevent brain lesions and neurological disabilities.
Neurodegeneration
Moreover, inflammation and glial cell metabolism are also intimately related to neurodegeneration. Neurodegeneration is defined as neuronal cell death and it has been strongly associated with the toxic accumulation of protein aggregates (namely a-synuclein forming Lewis bodies in Parkinson disease or tau and amyloid proteins in Alzheimer disease). Nevertheless and more recently, there is a great scientific discussion about the role of chronic neuroinflammation, whether is a cause or a consequence of neurodegeneration. This controversial subject will be approached for student to experiment biomedical scientific discussions. Still, dysfunctional clearance of neurotoxic aggregates by microglial phagocytosis will also be tackled.
With this curricular unit, students will understand that glia are key brain cells, controlling physiological and pathological process, that many underlying mechanisms of neural diseases also involve glial cells and that potential new therapeutic strategies should target glial cells.