ORCID Profile
0000-0002-2024-4083
Current Organisations
Deakin University
,
Barwon Health
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Publisher: Elsevier BV
Date: 12-2022
Publisher: Cold Spring Harbor Laboratory
Date: 20-03-2022
DOI: 10.1101/2022.03.20.485017
Abstract: Transposable elements (TEs) are a reservoir of new transcription factor binding sites for protein-coding genes 1–3 . Developmental programs that activate TE-derived regulatory elements could, in principle, manifest in lineage-specific TE mobility. While somatic LINE-1 (L1) retrotransposon insertions have been detected in human neurons 4–6 , the impact of L1 insertions on neurodevelopmental gene regulation, and whether L1 mobility is restricted to certain neuronal lineages, is unknown. Here, we reveal programmed L1 activation by SOX6, a transcription factor critical for parvalbumin (PV + ) interneuron development 7–9 . PV + neurons harbor unmethylated and euchromatic L1 promoters, express L1 mRNA, and permit L1 transgene mobilization in vivo . Elevated L1 expression in adult dentate gyrus PV + neurons is however attenuated by environmental enrichment. Nanopore sequencing of PV + neurons identifies unmethylated L1 loci providing alternative promoters to core PV + neuron genes, such as CAPS2. These data depict SOX6-mediated L1 activation as an ingrained component of the mammalian PV + neuron developmental program.
Publisher: Elsevier BV
Date: 2022
Publisher: Oxford University Press (OUP)
Date: 04-07-2022
DOI: 10.1093/BRAINCOMMS/FCAC205
Abstract: Huntington’s disease is a neurodegenerative disorder involving psychiatric, cognitive and motor symptoms. Huntington’s disease is caused by a tandem-repeat expansion in the huntingtin gene, which is widely expressed throughout the brain and body, including the gastrointestinal system. There are currently no effective disease-modifying treatments available for this fatal disorder. Despite recent evidence of gut microbiome disruption in preclinical and clinical Huntington’s disease, its potential as a target for therapeutic interventions has not been explored. The microbiota–gut–brain axis provides a potential pathway through which changes in the gut could modulate brain function, including cognition. We now show that faecal microbiota transplant (FMT) from wild-type into Huntington’s disease mice positively modulates cognitive outcomes, particularly in females. In Huntington’s disease male mice, we revealed an inefficiency of FMT engraftment, which is potentially due to the more pronounced changes in the structure, composition and instability of the gut microbial community, and the imbalance in acetate and gut immune profiles found in these mice. This study demonstrates a role for gut microbiome modulation in ameliorating cognitive deficits modelling dementia in Huntington’s disease. Our findings pave the way for the development of future therapeutic approaches, including FMT and other forms of gut microbiome modulation, as potential clinical interventions for Huntington’s disease.
Publisher: Elsevier BV
Date: 12-2022
Publisher: Elsevier
Date: 2022
Publisher: Springer International Publishing
Date: 2023
Location: Australia
No related grants have been discovered for Chloe Love.