Periodic Reporting for period 2 - EU-GliaPhD (Training, Research and Raising of Public Awareness in Cell Biology and Pathology of Neuroglia)
Periodo di rendicontazione: 2018-12-01 al 2021-06-30
The brain, as the site of our personality, is the most vulnerable part of our body. Alone in Europe (EU member states, Iceland, Norway, Switzerland) with a population of 514 million citizens the direct and indirect economic burden of brain diseases have been estimated to be 800 billion € per year. Since elucidation of the molecular and cellular mechanisms of brain function is an absolutely important prerequisite to understand the respective pathophysiological mechanisms and to develop novel and better brain therapies, training and education of neuroscientists will be of paramount importance to the future prosperous development of the European countries.
The EU-GliaPhD ITN network will address three scientific and eight training objectives:
(1) Identifying communication pathways between neurons and glia, analysis of the dysregulated brain using epilepsy as a central paradigm, and developing better research instrumentation and therapeutic targets.
(2) Advanced training in modern life science methodology, understanding of animal and disease models, skilled use of (in vivo) electrophysiological and imaging techniques, insights into product development of health and research industry, training in data analysis and statistical evaluation, modern supervision
and mentoring for fair leadership skills, awareness of intellectual property rights, and outreach activities for dissemination and communication to lay audiences.
The EU-GliaPhD ITN network will address three scientific and eight training objectives:
(1) Identifying communication pathways between neurons and glia, analysis of the dysregulated brain using epilepsy as a central paradigm, and developing better research instrumentation and therapeutic targets.
(2) Advanced training in modern life science methodology, understanding of animal and disease models, skilled use of (in vivo) electrophysiological and imaging techniques, insights into product development of health and research industry, training in data analysis and statistical evaluation, modern supervision
and mentoring for fair leadership skills, awareness of intellectual property rights, and outreach activities for dissemination and communication to lay audiences.
Within the first 12 months, the ESRs were successfully recruited. The EU-GliaPhD consortium organized several common meetings such as the kickoff meeting 2016 and the annual meeting 2017 and 2018 in Germany and France. In May 2018, an international conference “Novel Routes for the Analysis of Epilepsy” was organized on Malta. At these meetings the ESRs received training in neuroscience research and in scientific presentations to expert and lay audiences. Members of Caritas Malta Epilepsy Association and British Epilepsy Action mediated round-table discussions with people affected by epilepsy and family members. Sharing their personal experiences with epilepsy emphasized the importance of research to treat neuropathologies, but also to generate awareness and understanding for people living with epilepsy. Several interesting scientific observations were made and first publications appeared.
One type of the prime glial cells of the brain, the astrocytes form extensive networks with intercellular communication channels and, most importantly, modulate neurotransmission in adjacent neuronal microcircuits. Since astrocytes display particular electrophysiological properties, we developed specialized amplifiers to acquire intracellular recordings. In addition to astrocytes, the adult mouse cortex contains distinct types of interneurons that signal to astrocytes via the main inhibitory transmitter GABA and induce either depressing or potentiating Ca2+ signals to trigger graded astrocyte responses. Partners of the network discovered that limiting this GABAergic neuron to astrocyte communication can reduce epileptic activity in mice. Furthermore, the network has discovered and published crucial evidence on the involvement of inflammation, oxidative stress and iron metabolism in epileptogenesis. Great progress was also made in revealing that focal, non-convulsive seizures do transiently activate glial cells but do not contribute to permanent brain damage. The consortium also discovered new leads for therapeutic targets and a well-known class of drugs as potential novel therapeutic avenue for absence seizures.
In July 2019, the ESRs successfully organized the first special trainee symposium at the XIV European Meeting on Glial Cells in Health and Disease in Porto, where they presented their recent scientific advances to the glia community.
One type of the prime glial cells of the brain, the astrocytes form extensive networks with intercellular communication channels and, most importantly, modulate neurotransmission in adjacent neuronal microcircuits. Since astrocytes display particular electrophysiological properties, we developed specialized amplifiers to acquire intracellular recordings. In addition to astrocytes, the adult mouse cortex contains distinct types of interneurons that signal to astrocytes via the main inhibitory transmitter GABA and induce either depressing or potentiating Ca2+ signals to trigger graded astrocyte responses. Partners of the network discovered that limiting this GABAergic neuron to astrocyte communication can reduce epileptic activity in mice. Furthermore, the network has discovered and published crucial evidence on the involvement of inflammation, oxidative stress and iron metabolism in epileptogenesis. Great progress was also made in revealing that focal, non-convulsive seizures do transiently activate glial cells but do not contribute to permanent brain damage. The consortium also discovered new leads for therapeutic targets and a well-known class of drugs as potential novel therapeutic avenue for absence seizures.
In July 2019, the ESRs successfully organized the first special trainee symposium at the XIV European Meeting on Glial Cells in Health and Disease in Porto, where they presented their recent scientific advances to the glia community.
At the scientific level, the EU-GliaPhD consortium further deepened our understanding of brain function, in particular to understand the initiation and progression of epilepsy. This advancement was formed by combining and applying a series of latest-generation research instrumentations and methodologies. The consortium uncovered novel patho-mechanisms to pave the way for better therapies and answered pressing questions in the field. In addition, the consortium significantly contributed to the development of improved research instrumentation and methodologies. It is expected that some of the research results will have the potential for commercial and clinical exploitation.
The largest impact of the training consortium, however, was the education of early stage researchers enthusiastically starting their career. These young scientists will strengthen the European research area by their dedication to individual projects, but also by their commitment for international collaboration and open communication to the public.
Figure: In brains with epileptic seizures, the close cooperation of neurons and adjacent glial cells is impaired. Identifying the underlying molecular mechanisms will help to develop novel options for better therapies.
The largest impact of the training consortium, however, was the education of early stage researchers enthusiastically starting their career. These young scientists will strengthen the European research area by their dedication to individual projects, but also by their commitment for international collaboration and open communication to the public.
Figure: In brains with epileptic seizures, the close cooperation of neurons and adjacent glial cells is impaired. Identifying the underlying molecular mechanisms will help to develop novel options for better therapies.