UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

PAX6 , brain structure and function in human adults: advanced MRI in aniridia

Yogarajah, M; Matarin, M; Vollmar, C; Thompson, PJ; Duncan, JS; Symms, M; Moore, AT; ... Sisodiya, SM; + view all (2016) PAX6 , brain structure and function in human adults: advanced MRI in aniridia. Annals of Clinical and Translational Neurology , 3 (5) pp. 314-330. 10.1002/acn3.297. Green open access

[thumbnail of Yogarajah_et_al-2016-Annals_of_Clinical_and_Translational_Neurology.pdf]
Preview
Text
Yogarajah_et_al-2016-Annals_of_Clinical_and_Translational_Neurology.pdf - Published Version

Download (1MB) | Preview

Abstract

OBJECTIVE: PAX6 is a pleiotropic transcription factor essential for the development of several tissues including the eyes, central nervous system, and some endocrine glands. Recently it has also been shown to be important for the maintenance and functioning of corneal and pancreatic tissues in adults. We hypothesized that PAX6 is important for the maintenance of brain integrity in humans, and that adult heterozygotes may have abnormalities of cortical patterning analogous to those found in mouse models. METHODS: We used advanced magnetic resonance imaging techniques, including surface-based morphometry and region-of-interest analysis in adult humans heterozygously mutated for PAX6 mutations (n = 19 subjects and n = 21 controls). Using immunohistochemistry, we also studied PAX6 expression in the adult brain tissue of healthy subjects (n = 4) and patients with epilepsy (n = 42), some of whom had focal injuries due to intracranial electrode track placement (n = 17). RESULTS: There were significant reductions in frontoparietal cortical area after correcting for age and intracranial volume. A greater decline in thickness of the frontoparietal cortex with age, in subjects with PAX6 mutations compared to controls, correlated with age-corrected, accelerated decline in working memory. These results also demonstrate genotypic effects: those subjects with the most severe genotypes have the most widespread differences compared with controls. We also demonstrated significant increases in PAX6-expressing cells in response to acute injury in the adult human brain. INTERPRETATION: These findings suggest a role for PAX6 in the maintenance and consequent functioning of the adult brain, homologous to that found in other tissues. This has significant implications for the understanding and treatment of neurodegenerative diseases.

Type: Article
Title: PAX6 , brain structure and function in human adults: advanced MRI in aniridia
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/acn3.297
Publisher version: http://doi.org/10.1002/acn3.297
Language: English
Additional information: © 2016 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
URI: https://discovery.ucl.ac.uk/id/eprint/1485785
Downloads since deposit
83Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item