Toward the aim of reducing animal testing, innovative in vitro models are required. Here, this study proposes a novel smart polymeric microscaffold to establish an advanced 3D model of dopaminergic neurons. These scaffolds are fabricated with Ormocomp via Two-Photon Polymerization. The scaffolds are further enhanced by functionalization with fluorescent nanodiamonds (FNDs), which can serve as quantum nanosensors for both magnetic and temperature sensing. The material biocompatibility is tested using two different cell lines, SH-SY5Y and A431, with cell viability over 98%. A total of 69% of the FNDs are grafted on the structure compared to those that remained on the glass surface. Cells are tested with the scaffolds in several microenvironments, and the final assembly required for 3D quantum metrology experiments achieved 91% biocompatibility. Subsequently, embryoid bodies containing dopaminergic neurons, the cell type affected by Parkinson's disease (PD), are integrated with FND-functionalized scaffolds. This 3D model is successfully established, demonstrated by strong interactions between dopaminergic neurons and the scaffold, with the directional growth of neurites along the 3D scaffold. Ultimately, this study have developed a 3D platform that enables the readout of signaling in a model that holds great potential for future PD research.
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http://dx.doi.org/10.1002/adhm.202403875 | DOI Listing |
J Neurochem
January 2025
Institute for Physiology, University of Tübingen, Tübingen, Germany.
Parkinson's disease (PD) is a prevalent neurodegenerative disease caused by the death of dopaminergic neurons within the substantia nigra pars compacta (SNpc) region of the midbrain. Recent genomic and single cell sequencing data identified oligodendrocytes and oligodendrocyte precursor cells (OPCs) to confer genetic risk in PD, but their biological role is unknown. Although SNpc dopaminergic neurons are scarcely or thinly myelinated, there is a gap in the knowledge concerning the physiological interactions between dopaminergic neurons and oligodendroglia.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
January 2025
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro.
O-GlcNAcylation is a post-translational modification characterized by the covalent attachment of a single moiety of GlcNAc on serine/threonine residues in proteins. Tyrosine hydroxylase (TH), the rate-limiting step enzyme in the catecholamine synthesis pathway and responsible for production of the dopamine precursor, L-DOPA, has its activity regulated by phosphorylation. Here, we show an inverse feedback mechanism between O-GlcNAcylation and phosphorylation of TH at serine 40 (TH pSer40).
View Article and Find Full Text PDFBackground: Deficiency in the lysosomal enzyme, glucocerebrosidase (GCase), caused by mutations in the GBA1 gene, is the most common genetic risk factor for Parkinson's disease (PD). However, the consequence of reduced enzyme activity within neural cell sub-types remains ambiguous. Thus, the purpose of this study was to define the effect of GCase deficiency specifically in human astrocytes and test their non-cell autonomous influence upon dopaminergic neurons in a midbrain organoid model of PD.
View Article and Find Full Text PDFbioRxiv
January 2025
Nicholas School of the Environment, Duke University, Durham, North Carolina, USA.
Few of the many chemicals that regulatory agencies are charged with assessing for risk have been carefully tested for developmental neurotoxicity (DNT). To speed up testing efforts, as well as to reduce the use of vertebrate animals, great effort is being devoted to alternate laboratory models for testing DNT. A major mechanism of DNT is altered neuronal architecture resulting from chemical exposure during neurodevelopment.
View Article and Find Full Text PDFPeerJ
January 2025
Medical section, Jiang Ling County People's Hospital, Hubei, Jiangling County, Jingzhou City, China.
Background: This study investigates the protective properties of melatonin in an Parkinson's disease (PD) model, focusing on the underlying mechanisms involving heat shock proteins (HSPs).
Methods: Twelve adult male C57BL/6 mice were randomly divided into four groups (normal control, melatonin control, Parkinson's model, and melatonin treatment; = 3 per group) and housed in a single cage. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected intraperitoneally in the Parkinson's model and treatment groups to establish a subacute PD model, while controls received saline.
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