Chair: Bernadeta Szewczyk (Maj Institute of Pharmacology, PAS, Cracow, Poland)

Symposium 2: Zinc and the Brain: Unlocking Neurobiological Secrets

A symposium on Neurobiology and Health that explores the pivotal role of zinc in brain function, development, and disease. Leading researchers will discuss zinc’s impact on neural signaling, cognition, and its involvement in neurological disorders. Attendees will gain insights into cutting-edge findings on zinc’s molecular mechanisms and therapeutic potential.


Artur Krężel, Faculty of Biotechnology, University of Wroclaw, Poland

Zinc in motion: The role of zinc ions in cellular regulation and dynamics of zinc proteins

Homeostatic mechanisms regulate essential metal ions, including zinc, at specific cellular levels to ensure their physiological roles and prevent harmful effects. Zinc (formally Zn²⁺), a vital d-block metal ion, acts as a crucial catalytic and structural cofactor as well as a regulator in at least 3,000 human proteins.1 It exists in various chemical species within cells, influencing its biological roles, including those in neurons. Maintaining zinc homeostasis in eukaryotic cells allows zinc to participate in regulatory processes and signaling pathways1. In neurons, zinc is primarily stored in synaptic vesicles and released during neurotransmission, serving as a signaling molecule. The dynamic equilibrium between labile zinc and protein-bound zinc is maintained by metal-binding proteins, such as metallothioneins, and zinc transporters, which facilitate loading and release from cellular organelles2. These processes enable Zn²⁺ to function as second messengers in the cytosol, where concentrations are buffered to picomolar levels. Regulatory zinc ions interact with target proteins, including membrane receptors and enzymes, influencing gene expression and supporting enzymatic activity while protecting against oxidative stress. Understanding zinc speciation in neurons can provide insights into synaptic plasticity, neurodegenerative diseases, and potential therapeutic targets for zinc-related pathologies, highlighting the critical roles of zinc ions and metalloproteins in cellular regulation and neurological health.

References:
1. Maret W. The arcana of zinc. J. Nutr. 155, 669, 2025.
2. Krężel A, Maret W. The bioinorganic chemistry of mammalian metallothioneins. Chem. Rev. 121, 14594, 2021.


Jerome Ezan, PhD, Neurocentre Magendie – Inserm U1215, Bordeaux University, France

Impact of Zinc (dys)homeostasis on the development of the axon and its initial segment

Exploring the role of Zinc homeostasis during the formation of the axon intial segment (AIS).
Many neurodevelopmental disorders (NDDs), including autism spectrum disorders (ASDs), involve genetic and environmental factors like zinc deficiency, with comorbidities such as epilepsy. While Zinc’s role in synaptic transmission is well-studied1, its impact on the Axonal Initial Segment (AIS), the site of electrical signal transmission, remains unclear.
We recently identified the Planar Cell Polarity pathway (PCP) protein Prickle 2 (Pk2) as a key determinant of neuronal polarity, essential for AIS assembly and axonal excitability2.
By investigating the signaling pathways/kinases involved downstream of Zinc in neuronal polarization and AIS development, our study explores the hypothesis that Zinc and the PCP pathway may converge during this process.

References:
1. Błażewicz, A, Grabrucker A. M. Metal Profiles in Autism Spectrum Disorders: A Crosstalk between Toxic and Essential Metals. Int. J. Mol. Sci. 24, 308, 2022.
2. Dorrego-Rivas A, et al. The core PCP protein Prickle2 regulates axon number and AIS maturation by binding to AnkG and modulating microtubule bundling. Sci. Adv. 8, eabo6333, 2022.


Andreas M. Grabrucker, Professor, University of Limerick, Bernal Institute, Limerick, Ireland

Zinc as a regulator of neuroinflammatory signalling in Autism Spectrum Disorders

An impaired development of neural circuitry has been proposed as key pathology of Autism Spectrum Disorders (ASD). Astrocytes are important regulators of neuronal development and activity. Increased reactive astrocytes were reported in ASD and may significantly impact the balance between synapsę maturation and elimination, thereby modulating neural circuitry. Therefore, attenuating astrocyte activation may be an important approach for preventing and treating ASD. Intriguingly, zinc deficiency has been consistently linked to increased pro-inflammatory signalling and ASD1. We identified a cellular zinc-dependent signalling pathway that leads to astrocyte activation2. In this talk, the mechanism of how low zinc levels activate inflammatory-driven crosstalk between astrocytes and neurons is presented.

References:
1. Sauer AK, et al. Prenatal Zinc Deficient Mice as a Model for Autism Spectrum Disorders. Int J Mol Sci., 2022. doi: 10.3390/ijms23116082
2. Stanton J, et al. Zinc signaling controls astrocyte-dependent synapse modulation via the PAF receptor pathway, J Neurochem., 2024. doi: 10.1111/jnc.16252


Bernadeta Szewczyk, PhD, Maj Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland

Zinc Deficiency and Chronic Stress: Exploring Their Impact on Depression and Antidepressant Effectiveness

Clinical and preclinical studies provide evidence that chronic stress and nutritional deficits, particularly in dietary zinc (Zn) intake, may act as risk factors for the development of major depressive disorder (MDD). Additionally, there may be potential links between low serum Zn levels and the emergence of treatment-resistant depression. This talk will explore the effects of chronic restraint stress (CRS) and a low-zinc diet (ZnD) on the efficacy of antidepressants in mice. Furthermore, the underlying mechanisms responsible for these effects will be discussed.

References:
1. Pochwat B, et al. Combined hyperforin and lanicemine treatment instead of ketamine or imipramine restores behavioral deficits induced by chronic restraint stress and dietary zinc restriction in mice. Front Pharmacol., 2022, doi: 10.3389/fphar.2022.933364

Scroll to Top