This Research Topic is in collaboration with the
20th National Congress of the Italian Society for Neuroscience.
During the last two decades, advances in different areas of Neurosciences have clearly highlighted the complex nature of neuropsychiatric and neurodegenerative disorders. The proper assembly, maturation and maintenance of neuronal circuits underlying normal functioning of the nervous system require the execution of specific genetic programs, finely tuned in space and time.
The widespread detection of genes, mRNA, proteins, and metabolites has shed much light on relevant missteps in these delicate processes that may cause detrimental consequences for brain wiring and function. A clear role of cell-autonomous alterations, involving cell adhesion molecules, ion channels and intracellular pathways impinging on synaptic function is well established in neuropsychiatric diseases. Similarly, modifications in protein sequence and structure resulting in the accumulation of insoluble aggregates are widely acknowledged as culprits of most neurodegenerative disorders. On the other hand, the careful study of pathophysiological mechanisms that may translate genetic predisposition into full manifested disease phenotypes has revealed the involvement of non-genetic and non-neuronal factors in establishment and propagation of the damage from cell to network level. Indeed, current research is emphasizing the crucial role of epigenetic modifications, metabolic rewiring, brain-immune system cross-talk, glial cell functions, gut-to-brain axis, and blood-brain barrier, both in neuropsychiatric and neurodegenerative disorders. Importantly, these additional layers of complexity represent a rich interface between genetic variants and environmental stressors, whose nature and relevance are also being elucidated.
A critical factor in advancing the translation of this knowledge into enhanced diagnostic and therapeutic strategies lies in the accurate modeling of human disease pathogenesis. This necessitates comprehensively considering the complexity of underlying cellular and molecular interactions, as well as species-specific characteristics underlying the disease processes. Traditional cellular and animal models have so far been of utmost importance for understanding the molecular mechanisms underlying brain disorders. However, their actual translational value has also been questioned, due to the failure of several clinical trials resulting from pharmacological findings in animal models. Different cutting-edge strategies, including bioprinting, microfluidics 3D cell co-culture, human organoids, single cell multi-omics, in vivo functional imaging and multidimensional data integration have great potential to help filling the gap between in vitro and in vivo molecular-cellular-network responses, as well as to reduce the attrition rate between preclinical research and clinical applications. The complexity of these research tools also poses major challenges in terms of reliability and reproducibility.
The goal of this Research Topic is to provide an exclusive collection of research and discussions aimed at advancing the current understanding of state-of-the-art techniques and methodologies utilized for modeling neuropsychiatric and neurodegenerative disorders. In particular, our goal is to assemble a collection of cutting-edge communications, where the topics of interest include but are not limited to the following:
- Reproducing in vitro and in vivo critical aspects of the complex genetic, molecular and cellular interactions underlying neuropsychiatric and neurodegenerative disorders.
- Deeply characterizing the response of advanced in vitro models to genetic variation, environmental stressors and therapeutic agents.
- Identifying novel biomarkers, correlating with disease progression and response to therapeutic correction.
- Developing or implementing innovative procedures for computer simulation of different aspects of pathogenic cascades.
-Testing novel drug, gene and cellular therapy, using in vitro and in vivo models.
This Research Topic aims to attract Original Research, Methods, and Review papers from researchers in the field of neuropsychiatric, neurodevelopmental and neurodegenerative disorders. We encourage the exchange of important research, instruction, ideas and information on all aspects of the rapidly expanding area of brain disease modeling.