Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Targeting firing rate neuronal homeostasis can prevent seizures
  • Publication Type:
    Journal article
  • Authors:
    Mulroe F, Lin W-H, Mackenzie-Gray Scott C, Aourz N, Fan YN, Coutts G, Parrish RR, Smolders I, Trevelyan A, Wykes R, Allan S, Freeman S, Baines RA
  • Publisher:
    The Company of Biologists
  • Publication date:
  • Journal:
    Disease Models and Mechanisms
  • Status:
  • Print ISSN:
  • Language:
  • Keywords:
    Drosophila, Seizure, Neuronal homeostasis, Mouse, PUMILIO, Translational regulation
  • Notes:
    © 2022. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Manipulating firing-rate neuronal homeostasis, which enables neurons to regulate their intrinsic excitability, offers an attractive opportunity to prevent seizures. However, to date, no drug-based interventions have been reported that manipulate this type of neuronal homeostatic mechanism. Here, we use a combination of Drosophila and mouse and, in the latter, both a pentylenetetrazole (PTZ) induced seizure model, and an electrically induced seizure model for refractory seizures to evaluate anticonvulsant efficacy of a novel class of anticonvulsant compounds, based on 4-tert-butyl-benzaldehyde (4-TBB). The mode-of-action includes increased expression of the firing rate homeostatic regulator PUMILIO (PUM). Knock-down of PUM expression, in Drosophila, blocks anticonvulsive effects of 4-TBB, whilst analysis of validated PUM targets in mouse brain show significant reductions following exposure to this compound. A structure-activity study identifies the active parts of the molecule and, further, shows the pyrazole analogue demonstrates highest efficacy, being active against both PTZ-, and electrically-induced, seizures. This study provides a proof-of-principle that anticonvulsant effects can be achieved through regulation of firing rate neuronal homeostasis and identifies a possible chemical compound for future development.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Clinical & Experimental Epilepsy
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by