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

Jaehne, Emily J., Kent, Jessica N., Antolasic, Emily J., Wright, Bradley J., Spiers, Jereme G., Creutzberg, Kerstin C., De Rosa, Federico, Riva, Marco A., Sortwell, Caryl E., Collier, Timothy J., and van den Buuse, Maarten (2022) Behavioral phenotyping of a rat model of the BDNF Val66Met polymorphism reveals selective impairment of fear memory. Translational Psychiatry, 12. 93.

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Abstract

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.

Item ID: 73293
Item Type: Article (Research - C1)
ISSN: 2158-3188
Copyright Information: © The Author(s) 2022.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC APP1187652
Date Deposited: 30 Mar 2022 08:42
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320221 Psychiatry (incl. psychotherapy) @ 50%
52 PSYCHOLOGY > 5202 Biological psychology > 520201 Behavioural genetics @ 50%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280121 Expanding knowledge in psychology @ 100%
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