Nina Vardjan, Slovenia

Faculty of Medicine, University of Ljubljana Institute of Pathophysiology

Nina Vardjan is Associate Professor in Biochemistry and a coordinating director of the Neuroglia Projects in the Laboratory of Neuroendocrinology-Molecular Cell Physiology at Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana and in the Laboratory for Cell Engineering at Celica Biomedical, Slovenia. She obtained her B.Sc. in Microbiology at the Biotechnical Faculty, University of Ljubljana, Slovenia in 1999. In 2003 she received her Ph.D. in Biochemistry and Molecular Biology at the Post-graduate Study of Biomedicine, Faculty of Medicine, University of Ljubljana, Slovenia. From 2006, she is involved in teaching (General Physiology, Cell Physiology, Molecular Physiology, Cell Engineering) at the Faculty of Chemistry and Chemical Technology and Biotechnical Faculty, University of Ljubljana. Her research is focused on astroglial physiology in brain health and disease. She has published more than 50 peer-reviewed paper, has h-index (2021) of 22, and is author of two patents. She is the president of the Slovenian Physiological Society, member of FEPS and IUPS, and a core group member of the COST action European Research Network on Signal Transduction.

Presenter of 2 Presentations

Conference Calendar

ASTROCYTES WITH ALS/FTD-LINKED CYTOPLASMIC TDP-43 INCLUSIONS EXHIBIT DYSREGULATED NORADRENERGIC SIGNALING AND METABOLISM

Session Name

TDP-43 IN ALS AND FTD

Session Type

SYMPOSIUM

Date

11.03.2021, Thursday

Session Time

10:00 - 11:45

Room

On Demand Symposia C

Lecture Time

11:00 - 11:15

Presenter

Nina Vardjan, Slovenia

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Abstract

Abstract

Aims

Cytoplasmic TDP-43 (TAR DNA-binding protein 43) inclusions are the pathological hallmark in most cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). They are found not only in neurons, but also in astrocytes, which supply neurons with nutrients. Neuronal metabolism largely depends on the activation of astroglial adrenergic receptors, the primary target of noradrenaline, which in astrocytes triggers Ca²⁺ and cAMP signalling and augments aerobic glycolysis and lactate production. Cytoplasmic TDP-43 inclusions in astrocytes alone can cause motor neuron death, however, it is unclear whether this affects astroglial metabolism and ultimately the capacity of astrocytes to metabolically support neurons.

Methods

By using fluorescent dyes, genetically encoded FRET nanosensors and real-time confocal microscopy we measured the dynamics of Ca²⁺/cAMP signalling and lipid droplet (LD) and glucose metabolisms in isolated cortical astrocytes expressing the inclusion-forming C-terminal fragment of TDP-43 or wild-type TDP-43.

Results

The accumulation of LDs was increased in astrocytes with TDP-43 inclusions vs. astrocytes expressing wild-type TDP-43. These cells also exhibited reduced noradrenaline-mediated Ca²⁺ and cAMP signalling, likely due to the downregulation of β₂-adrenergic receptors. Although noradrenaline-triggered increase in intracellular lactate was similar in astrocytes with and without TDP-43 inclusions, the probability of activating aerobic glycolysis was facilitated in astrocytes with TDP-43 inclusions, while lactate MCT1 transporters were downregulated.

Conclusions

Our results show that, while noradrenergic signalling is reduced in astrocytes with TDP-43 inclusions, aerobic glycolysis and LD accumulation are facilitated, suggesting dysregulated metabolism that may affect astroglial metabolic support of neurons in ALS and FTD.

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