Ageing increases UT-B urea transporter protein abundance throughout the mouse brain

Neuroplasticity in Brain Health and Disease (Newcastle University, UK) (2024) Proc Physiol Soc 57, C26

Poster Communications: Ageing increases UT-B urea transporter protein abundance throughout the mouse brain

Farhana Pinki1, Lauren McKeever1, Derek Costello1, Gavin Stewart1,

1School of Biology and Environmental Science, University College Dublin Dublin Ireland, 2School of Biomedical and Biomolecular Sciences, University College Dublin Dublin Ireland,

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Facilitative UT-B urea transporters in the brain play an important role in regulating levels of urea in various cell types, including astrocytes. Numerous studies have reported increased UT-B RNA expression with ageing and in a variety of neurological disorders, such as Alzheimer’s Disease, particularly in the hippocampal regions. However, much less in known about the effects of these conditions on UT-B transporter protein abundance and function. This current study therefore compared the levels of both UT-B RNA and UT-B protein in young (3-5 months old) and aged (18-24 months old) male C57BL/6 mice. Animals were euthanized to provide tissue for undergraduate teaching activities. Postmortem brain tissue was subsequently isolated for research purposes in accordance with a tissue-sharing initiative, following approval of the UCD Animals Ethics Committee. All data shown as mean ± S.E.M. As expected, endpoint RT-PCR experiments initially showed that the UT-B/GAPDH RNA expression ratio increased in aged mouse hippocampus (0.27 ± 0.12 vs 0.95 ± 0.09, P=0.0131, N=3, unpaired T-Test). Importantly, this change was confirmed at the protein abundance level, as western blotting experiments revealed that the 30-35 kDa UT-B1 signal/protein ratio was also significantly increased in aged mouse hippocampus (0.76 ± 0.21 vs 1.83 ± 0.43, P=0.0426, N=5-6, unpaired T-Test). Further investigations showed similar increases in UT-B1 protein abundance in the cerebellum, frontal cortex and occipital cortex regions (all P<0.05, N=3, unpaired T-Test). In contrast, no such changes occurred in the abundance of MCT1 short chain fatty acid transporters (all NS, N=3, unpaired T-Test). These data therefore confirmed that specific increases in UT-B1 protein abundance occur throughout the regions of the aged mouse brain. Further studies are now needed to investigate both the precise cellular location and functional consequence of these increased UT-B1 protein levels.



Where applicable, experiments conform with Society ethical requirements.

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