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  • Wetten, AaronTranslational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom (author)

Neurosteroid activation of gaba-a receptors : a potential treatment target for symptoms in primary biliary cholangitis?

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • Hindawi Publishing Corporation,2022
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-202002
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-202002URI
  • https://doi.org/10.1155/2022/3618090DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Background and Aims: A third of patients with primary biliary cholangitis (PBC) experience poorly understood cognitive symptoms, with a significant impact on quality of life (QOL), and no effective medical treatment. Allopregnanolone, a neurosteroid, is a positive allosteric modulator of gamma-aminobutyricacid-A (GABA-A) receptors, associated with disordered mood, cognition, and memory. This study explored associations between allopregnanolone and a disease-specific QOL scoring system (PBC-40) in PBC patients.Method: Serum allopregnanolone levels were measured in 120 phenotyped PBC patients and 40 age and gender-matched healthy controls. PBC subjects completed the PBC-40 at recruitment. Serum allopregnanolone levels were compared across PBC-40 domains for those with none/mild symptoms versus severe symptoms.Results: There were no overall differences in allopregnanolone levels between healthy controls (median = 0.03 ng/ml (IQR = 0.025)) and PBC patients (0.031 (0.42), p = 0.42). Within the PBC cohort, higher allopregnanolone levels were observed in younger patients (r (120) = -0.53, p < 0.001) but not healthy controls (r (39) = -0.21, p = 0.21). Allopregnanolone levels were elevated in the PBC-40 domains, cognition (u = 1034, p = 0.02), emotional (u = 1374, p = 0.004), and itch (u = 795, p = 0.03). Severe cognitive symptoms associated with a younger age: severe (50 (12)) vs. none (60 (13); u = 423 p = 0.001).Conclusion: Elevated serum allopregnanolone is associated with severe cognitive, emotional, and itch symptoms in PBC, in keeping with its known action on GABA-A receptors. Existing novel compounds targeting allopregnanolone could offer new therapies in severely symptomatic PBC, satisfying a significant unmet need.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Ogle, LauraTranslational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom (author)
  • Mells, GeorgeDepartment of Human Genetics, University of Cambridge, Cambridge, United Kingdom (author)
  • Hegade, Vinod S.Leeds Liver Unit, St James' University Hospital, Leeds, United Kingdom (author)
  • Jopson, LauraTranslational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom (author)
  • Corrigan, MargaretLiverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom (author)
  • Palmer, JeremyTranslational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom (author)
  • Johansson, MajaUmecrine Cognition AB, Solna, Sweden (author)
  • Bäckström, TorbjörnUmeå universitet,Obstetrik och gynekologi,Umecrine Cognition AB, Solna, Sweden(Swepub:umu)toba0001 (author)
  • Doverskog, MagnusUmecrine Cognition AB, Solna, Sweden (author)
  • Jones, David E. J.Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom (author)
  • Dyson, Jessica K.Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom (author)
  • Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United KingdomDepartment of Human Genetics, University of Cambridge, Cambridge, United Kingdom (creator_code:org_t)

Related titles

  • In:Canadian journal of gastroenterology & hepatology: Hindawi Publishing Corporation20222291-27892291-2797

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