Endocrine Abstracts

Adequate thyroid hormone levels are crucial for cell homeostasis in the adult human brain. To supply neuronal and glial cells, thyroid hormone (TH) transporters such as the monocarboxylate transporter 8 (MCT8) are required. While implications in TH levels in the human brain seem to play a role in neurodegenerative diseases such as Alzheimer’s disease (AD), altered expression of TH transporters has not been described yet. Our study therefore aimed to evaluate MCT8 expression levels in different brain regions and cell types in adult human post mortem brain samples without pathological alterations and such affected by AD. Following our evaluations, we demonstrated proteomic and transcriptomic MCT8 expression in astrocytes, various neuronal subgroups and endothelial cells in 8 different brain regions (inter alia hippocampus, occipital, motor, prefrontal and temporal cortex). Performing colocalization studies using both in situ hybridization and immunohistochemistry, we showed that cells containing RNA of the SLC16A2 gene (MCT8 coding) also express the proteomic correlate. By using different MCT8 antibodies, we detected distinct staining patterns in MCT8-positive neurons which we investigated using stimulated emission depletion (STED) super-resolved microscopy. Most cells showed signals located at the cellular membrane while others showed perinuclear signals. To examine whether the progression of AD is associated with up- or down-regulation of MCT8 expression levels, we performed Braak staging of neurofibrillary degeneration on all our brain samples and divided them in a Braak-high and a Braak-low group. We found no evident qualitative differences in MCT8 staining patterns and strength between these groups. To further investigate MCT8 expression dependency, we are currently developing a data analysis pipeline for publicly available single cell/single nucleus RNA sequencing (sc/snRNAseq) data of previous studies on human brain tissue. Our findings suggest that MCT8 is of relevance even in the adult and elderly human brain as the TH transporter is expressed in most endothelial cells and a high number of glial and neuronal cells in different brain regions. While we found no qualitative differences in MCT8 staining patterns between the samples affected and not affected by AD, local changes in TH availability cannot be omitted. We expect that by analysing various sc/snRNAseq datasets we aim to clarify whether TH-related genes are dysregulated in neuronal and glial cells of AD patients.