Title of my talk: Glia in Action: Astrocytes in Physiological and Pathological Stress.

AbstractStress is an adaptive physiological reaction of the organism to altered environment. However, in excess, stress may lead to pathological changes, such as depression. Astrocytes respond to primary mediators of stress, i.e. noradrenaline and glucocorticoids, and they do so in various modes and across time scales. Noradrenergic signaling is related to general arousal. We found that direct action of noradrenaline in astrocytes enables their responsiveness to sensory inputs. This observation shows that astrocytes can integrate the information on sensory and neuromodulatory signals in a range of seconds. Further, we have shown that astrocytes are a major cellular locus of glucocorticoid transcriptional action in the brain. These effects are mediated through glucocorticoid receptors and occur within several hours from stress experience. Additionally, we found that chronic stress alters circadian profile of astrocytes gene expression. We concluded that astrocytes are a crucial cellular locus of molecular effects of stress in the brain. A key question remains on the relevance of astrocytes for neurobiological effects of chronic stress. With that respect we revealed that glucocorticoid signaling in astrocytes is required for aversive memory formation. To better understand underlying molecular mechanisms, we performed a systematic survey of glucocorticoid effects in astrocytes and found specific changes in their metabolic profile. We are currently exploring the impact of selected pathways loss-of-function and rescue in cell culture systems. In parallel, we employ a combination of tools enabling astrocyte-specific gene manipulation with unprecedented precision, along with monitoring astrocyte physiology in awake, behaving mice. Results of our work will shed new light on dysfunctions elicited by chronic stress in a glial compartment. This knowledge shall result in designing novel therapeutic strategies for stress-related diseases.

Work history:

2016 onwards: Group Leader, Brain Microcircuits in Psychiatric Diseases; BioMed X Innovation Center, Heidelberg.

2012-2016: Postdoc (Marie-Curie Intra-European Fellowship) VIB, KU Leuven, Belgium, Dept. Glia Biology, Head: Dr M. Holt

2007-2012: Postdoc (Young Investigator Award, Ministry of Science and Higher Education) Inst. Pharmacology, PAS, Cracow, Dept. Molecular Neuropharmacology, Head: Dr R. Przewłocki

2002-2007: PhD thesis ‘New transgenic mouse models for astrocyte-specific, inducible somatic mutagenesis’ Univ. Strasbourg, INCI, Supervisor: Dr F.W. Pfrieger.

Key publications:

Tertil M*, Skupio U*, …, Slezak M. Glucocorticoid receptor signaling in astrocytes is required for aversive memory formation. (2018) Transl Psych.

Slezak M*, Kandler S*, …, Bonin V, Holt MG. Distinct mechanisms for visual and motor related astrocyte responses in mouse visual cortex. (2018) bioRxiv

Slezak M*, de Vin F*, …, Holt MG. Flexible, fast and selective genetic manipulation of the vertebrate CNS with misPiggy. (2018) bioRxiv

Slezak M*, Grosche A*, Niemiec A*, …, Pfrieger FW. (2012) Relevance of exocytotic glutamate release from retinal glia. Neuron.

Slezak M, …, Pfrieger FW. (2007) Transgenic mice for conditional gene manipulation in astroglial cells. Glia.