Harris, A. P., Lennen, R. J., Brydges, Nichola, Jansen, M. A., Pernet, C. R., Whalley, H. C., Marshall, I., Baker, S., Basso, A. M., Day, M., Holmes, M. C. and Hall, Judith Elizabeth ORCID: https://orcid.org/0000-0002-6770-7372 2016. The role of brain derived neurotrophic factor in learned fear processing: an awake rat fMRI study. Genes, Brain and Behavior 15 (2) , pp. 221-230. 10.1111/gbb.12277 |
Abstract
Brain-derived neurotrophic factor (BDNF) signaling is implicated in the aetiology of many psychiatric disorders associated with altered emotional processing. Altered peripheral (plasma) BDNF levels have been proposed as a biomarker for neuropsychiatric disease risk in humans. However the relationship between peripheral and central BDNF levels and emotional brain activation is unknown. We used heterozygous BDNF knockdown rats (BDNF+/- ) to examine the effects of genetic variation in the BDNF gene on peripheral and central BDNF levels and emotional brain activation as assessed by awake fMRI. BDNF+/- and control rats were trained to associate a flashing light (conditioned stimulus; CS) with foot-shock, and brain activation in response to the CS was measured 24h later in awake rats using fMRI. Central and peripheral BDNF levels were decreased in BDNF+/- rats compared to control rats. Activation of fear circuitry (amygdala, periaqueductal gray, granular insular) was seen in control animals, however activation of this circuitry was absent in BDNF+/- animals. Behavioral experiments confirmed impaired conditioned fear responses in BDNF+/- rats, despite intact innate fear responses. These data confirm a positive correlation (r = 0.86, 95% CI [0.55, 0.96]; P = 0.0004) between peripheral and central BDNF levels and indicate a functional relationship between BDNF levels and emotional brain activation as assessed by fMRI. The results demonstrate the use of rodent fMRI as a sensitive tool for measuring brain function in preclinical translational studies using genetically modified rats and support the use of peripheral BDNF as a biomarker of central affective processing.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Biosciences |
Subjects: | Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
Uncontrolled Keywords: | Amygdala; awake rat fMRI; BDNF; Pavlovian conditioning; transgenic rat |
Publisher: | Wiley-Blackwell |
ISSN: | 1601-1848 |
Funders: | AbbVie, CCACE, BHF CoRE, Wellcome Trust Strategic Award. Grant Number: 503147, MRC Centre Grant. Grant Number: G0800509, BBSRC, MRC, NMHRI |
Date of Acceptance: | 17 November 2015 |
Last Modified: | 31 Oct 2022 10:45 |
URI: | https://orca.cardiff.ac.uk/id/eprint/86046 |
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