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The role of brain-derived neurotrophic factor in learned fear processing: an awake rat fMRI study.

ABSTRACT: Brain-derived neurotrophic factor (BDNF) signaling is implicated in the etiology 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 functional magnetic resonance imaging (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 24 h later in awake rats using fMRI. Central and peripheral BDNF levels were decreased in BDNF(+/-) rats compared with 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% confidence interval (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.

SUBMITTER: Harris AP

PROVIDER: S-EPMC4819698 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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The role of brain-derived neurotrophic factor in learned fear processing: an awake rat fMRI study.

Harris A P AP Lennen R J RJ Brydges N M NM Jansen M A MA Pernet C R CR Whalley H C HC Marshall I I Baker S S Basso A M AM Day M M Holmes M C MC Hall J J

Genes, brain, and behavior 20160105 2

Brain-derived neurotrophic factor (BDNF) signaling is implicated in the etiology 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 gen ...[more]

PMID: 26586578

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Project description:Several studies have implied a role of brain-derived neurotrophic factor (BDNF) in abdominal pain modulation in irritable bowel syndrome (IBS). The aim of this study was to establish BDNF protein expression in human colonic biopsies and to show variation in IBS compared to controls. BDNF protein and mRNA levels were correlated with IBS symptom severity based on the IBS-symptom severity score (IBS-SSS). Biopsies from the descending colon and IBS-SSS were obtained from 10 controls and 20 IBS patients. Total protein of biopsies was extracted and assessed by ELISA and Western Blot. Total mRNA was extracted and gene expression measured by nCounter analysis. In IBS patients, symptom severity scores ranged from 124 to 486 (mean ± sem: 314.2 ± 21.2, >300 represents severe IBS) while controls ranged from 0 to 72 (mean ± sem: 27.7 ± 9.0, <75 represents healthy subjects, p < 0.001). IBS patients reported significantly more food malabsorption, former abdominal surgery and psychiatric comorbidities. BDNF protein was present in all samples and did not differ between IBS and controls or sex. Subgroup analysis showed that female IBS patients expressed significantly more BDNF mRNA compared to male patients (p < 0.05) and male IBS-D patients had higher IBS symptom severity scores and lower BDNF mRNA and protein levels compared to male controls (p < 0.05). Scatter plot showed a significant negative correlation between IBS-SSS and BDNF mRNA levels in the cohort of male IBS-D patients and their male controls (p < 0.05). We detected a high proportion of gastrointestinal surgery in IBS patients and confirmed food intolerances and psychiatric diseases as common comorbidities. Although in a small sample, we demonstrated that BDNF is detectable in human descending colon, with higher BDNF mRNA levels in female IBS patients compared to males and lower mRNA and protein levels in male IBS-D patients compared to male controls. Further research should be directed toward subgroups of IBS since their etiologies might be different.

Dataset Information

The role of brain-derived neurotrophic factor in learned fear processing: an awake rat fMRI study.

Publications

The role of brain-derived neurotrophic factor in learned fear processing: an awake rat fMRI study.

Similar Datasets

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