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Insulin resistance compromises midbrain organoid neuronal activity and metabolic efficiency predisposing to Parkinson's disease pathology.
J Tissue Eng
January 2025
Developmental and Cellular Biology, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Growing evidence indicates that type 2 diabetes (T2D) is associated with an increased risk of developing Parkinson's disease (PD) through shared disease mechanisms. Studies show that insulin resistance, which is the driving pathophysiological mechanism of T2D plays a major role in neurodegeneration by impairing neuronal functionality, metabolism and survival. To investigate insulin resistance caused pathological changes in the human midbrain, which could predispose a healthy midbrain to PD development, we exposed iPSC-derived human midbrain organoids from healthy individuals to either high insulin concentration, promoting insulin resistance, or to more physiological insulin concentration restoring insulin signalling function.
View Article and Find Full Text PDFThe multifaceted role of the inferior colliculus in sensory prediction, reward processing, and decision-making.
Elife
January 2025
Department of Anesthesia, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
The inferior colliculus (IC) has traditionally been regarded as an important relay in the auditory pathway, primarily involved in relaying auditory information from the brainstem to the thalamus. However, this study uncovers the multifaceted role of the IC in bridging auditory processing, sensory prediction, and reward prediction. Through extracellular recordings in monkeys engaged in a sound duration-based deviation detection task, we observed a 'climbing effect' in neuronal firing rates, indicative of an enhanced response over sound sequences linked to sensory prediction rather than reward anticipation.
View Article and Find Full Text PDFMeasurement of inferior colliculus volume based on MRI image stacks and its relationship with age and hearing status.
PLoS One
January 2025
Department of Otolaryngology, University Hospital Regensburg, Regensburg, Germany.
The inferior colliculus is a key nucleus in the central auditory pathway, integrating acoustic stimuli from both cochleae and playing a crucial role in sound localization. It undergoes functional and structural development in childhood and experiences age-related degeneration later in life, contributing to the progression of age-related hearing loss. This study aims at finding out, whether the volume of the human inferior colliculus can be determined by analysis of routinely performed MRIs and whether there is any age-related variation.
View Article and Find Full Text PDFInteractions of Oligodendrocyte Precursor Cells and Dopaminergic Neurons in the Mouse Substantia Nigra.
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 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.
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