Behavioral phenotyping of a rat model of the BDNF Val66Met polymorphism reveals selective impairment of fear memory

Jaehne, Emily; Kent, JN; Antolasic, Emily; Wright, Bradley; Spiers, Jereme; Creutzberg, KC; De Rosa, F; Riva, MA; Sortwell, CE; Collier, TJ; van den Buuse, Maarten

doi:10.26181/19470068.v1

1197024_Jaehne,E.J_2022.pdf (1.47 MB)

Behavioral phenotyping of a rat model of the BDNF Val66Met polymorphism reveals selective impairment of fear memory

journal contribution

posted on 2022-03-31, 00:09 authored by Emily JaehneEmily Jaehne, JN Kent, Emily AntolasicEmily Antolasic, Bradley WrightBradley Wright, Jereme SpiersJereme Spiers, KC Creutzberg, F De Rosa, MA Riva, CE Sortwell, TJ Collier, Maarten van den BuuseMaarten van den Buuse

The common brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with reduced activity-dependent BDNF release and increased risk for anxiety disorders and PTSD. Here we behaviorally phenotyped a novel Val66Met rat model with an equivalent valine to methionine substitution in the rat Bdnf gene (Val68Met). In a three-day fear conditioning protocol of fear learning and extinction, adult rats with the Met/Met genotype demonstrated impaired fear memory compared to Val/Met rats and Val/Val controls, with no genotype differences in fear learning or extinction. This deficit in fear memory occurred irrespective of the sex of the animals and was not seen in adolescence (4 weeks of age). There were no changes in open-field locomotor activity or anxiety measured in the elevated plus maze (EPM) nor in other types of memory measured using the novel-object recognition test or Y-maze. BDNF exon VI expression in the dorsal hippocampus was higher and BDNF protein level in the ventral hippocampus was lower in female Val/Met rats than female Val/Val rats, with no other genotype differences, including in total BDNF, BDNF long, or BDNF IV mRNA. These data suggest a specific role for the BDNF Met/Met genotype in fear memory in rats. Further studies are required to investigate gene-environment interactions in this novel animal model.

Funding

The authors are grateful to Prof Cynthia Shannon Weickert (NeuRA, Sydney, Australia) for valuable suggestions regarding data interpretation. These studies were supported in part by an internal grant from La Trobe University (Research Focus Area, Understanding Disease 2016), a Manchester Metropolitan University and La Trobe University Collaborative Research Grant (2019), internal grant support from the School of Psychology and Public Health, La Trobe University (2019), internal student support from the School of Psychology and Public Health, La Trobe University (2016, 2017 and 2018), and an Ideas Grant from the National Health and Medical Research Council of Australia (APP1187652).

History

Publication Date

2022-03-07

Journal

Translational Psychiatry

Volume

12

Issue

1

Article Number

93

Pagination

11p.

Publisher

Springer Nature

ISSN

2158-3188

Rights Statement

© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article ’ s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.