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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

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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.


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).


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Translational Psychiatry





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Springer Nature



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