Konstantinos Ampatzis

Bakgrund: Cardiovascular homeostasis is vital for vertebrates, requiring dynamic regulation of heart function. The autonomic nervous system (ANS), traditionally seen as a balance between sympathetic and parasympathetic branches, modulates heart rate. However, this view overlooks the complexity of cardiac control. Recent work from the Ampatzis lab has identified the intracardiac nervous system (IcNS) a network of neurons on the heart's surface as a critical yet underexplored regulator of cardiac activity. These neurons, some pacemaker-like, modulate heart rhythm and may adapt following injury. We hypothesize that IcNS dysfunction contributes to age-related cardiovascular decline and neurodegeneration, yet the mechanisms behind its plasticity and role in ageing remain unknown. Målsättning: We aim to investigate the role of IcNS in heart repair and age-associated cardiac dysfunction. 1. Define IcNS plasticity following heart injury and its role in cardiac regeneration Hypothesis: Cardiac injury triggers IcNS remodeling, leading to the release of specific signaling molecules that promote cardiomyocyte proliferation and heart repair. Expected Outcome: Identification of neurogenic pathways essential for regeneration. 2. Examine how ageing affects IcNS neurons and their function. Hypothesis: Ageing impairs IcNS structure and function, disrupting autonomic control and exacerbating dysfunction. Expected Outcome: Identification of ageing-related genes and pathways affecting regeneration. Arbetsplan: We will use a multidisciplinary strategy combining anatomy, physiology, genetics, and advanced imaging. Induce heart injury to study IcNS remodeling. Use neurochemical profiling and electrophysiology to characterize repair-related neurons. Apply optogenetics, ablation, and pharmacological tools to modulate IcNS activity and evaluate effects on regeneration. Perform longitudinal analyses to track IcNS changes with age. Use single-cell transcriptomics and functional assays to identify age-related dysfunction. Correlate IcNS decline with cardiovascular pathology to explore links to neurodegeneration. Betydelse: This study will define the IcNS as a key player in cardiac health and ageing. It will identify new therapeutic targets, connect neurodegeneration with heart disease, and establish zebrafish as a model for neural plasticity and repair laying a foundation for future cardiac therapies.

Spaceflight represents an extreme environment, characterized by microgravity and space radiation, offering the possibility to study brain plasticity under abnormal conditions. Previous studies have indicated that spaceflight alters the human gene expression. In addition, a recent study from our laboratory has identified that space travel affect cellular mechanisms in mouse brain that are known to be involved in pathophysiological conditions like neurodegenerative disorders.This project aims to discover new insights relatively to brain adaptability leveraging spaceflight as an extreme environment. We will reveal the detailed molecular alterations induced by space travel on brain by studying unique samples deriving from mice that were flown on the International Space Station. To this end, we will employ state-of-the-art technologies, i.e., single-cell multiomics, Spatial Transcriptomics and spatial mass spectrometry, to decode the alterations of the brain molecular programs caused by permanence in space. Moreover, we will compare the detected molecular signatures to the ones observed in brains of Parkinson´s disease mouse models.Overall, this study holds the potential to provide novel insights to formulate new and fundamental hypotheses on brain plasticity opening up new strategies to improve human wellbeing and life quality.

An essential determinant of a neuron’s functionality is its neurotransmitter phenotype. While the prevailing view is that neurotransmitters are fixed and determined during development, our previous work in zebrafish supports a growing body of evidence suggests that neurons retain the ability to switch between different neurotransmitters. In the context of this research proposal, we will address the critical question: Do changes in neurotransmission can contribute to spinal cord regeneration after the injury? The architecture, connectivity, and plasticity of spinal circuits may hold the answer to this fundamental question. For this, we will take a multidisciplinary approach that combines an innovative and comprehensive set of state-of-the-art techniques from systems neuroscience and the stem cell research fields, in adult zebrafish. An animal model with extensive regeneration capacity providing an experimentally tractable system for electrophysiology, pharmacology, anatomy, molecular profiling, and genetics. By a combination of these methods, we will explore the neuronal and non-neuronal functions of spinal neurotransmission and its dynamics during spinal cord restoration. We expect our results to reveal new principles of neuroplasticity with a significant impact on our understanding of the normal and pathological state of the central nervous system. Hence, our overall objective is to promote spinal cord regeneration and reinstate normal locomotor behavior.