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Hernandez, Alejandro Ivan
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Spring 2023
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2023-03-03
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Autism spectrum disorder (ASD) is a group of disorders characterized by social communication deficits, increased repetitive behaviors, and cognitive deficits. [1, 2]. Post-mortem brain studies of ASD patients show smaller hippocampus size, and the
volume and the size of both the nucleus and the cytoplasm are smaller [3, 4, 5, 6]. Ribosome biogenesis is one of the cellular functions that influence a cell's growth and volume [7] and is essential for learning and memory. The above observation suggests ribosome biogenesis might be dysregulated, leading to social and cognitive impairment. Using male BTBR T+ Itpr3tf/J (BTBR) mice, a model that reproduces most of the core behavioral phenotypes of ASD, we determined the role of ribosomal RNA
synthesis, required for ribosome biogenesis and its impact on cognition, social and repetitive behavior. Presented here, data show that ribosomal RNA expression is decreased in the dorsal hippocampus of BTBR mice compared with B6 mice. Further
3BDO treatment leads to pharmacological up-regulation of ribosomal RNA synthesis, improved learning, and reduced repetitive behavior in BTBR mice. Suggesting that newly synthesized ribosomal RNA plays an essential role in learning and memory in
ASD mice model (BTBR). We also found that there is a reduction of learning-induced ribosomal RNA variant expression in BTBR mice, and 3BDO treatment led to differential expression of the ribosomal variant in BTBR. This might imply that newly
synthesized ribosomal RNA variants are essential for producing qualitatively different ribosomes, which might be required to improve behavioral deficits in the ASD mouse model. Overall, this thesis provides a new perspective on how ribosome biogenesis plays an essential role in ASD, and this data might help pave a road toward therapeutic intervention.
Citation
Phatarpekar, Shwetha S. (2023), The Role of ribosomal RNA in Autism spectrum disorder (ASD), [Doctoral Dissertation, SUNY Downstate Health Sciences University], SUNY Open Access Repository. https://soar.suny.edu/handle/20.500.12648/14849