Proteolytic cleavage of proBDNF into mature BDNF in the basolateral amygdala is necessary for defeat-induced social avoidance

Dulka, Brooke N.; Ford, Ellen C.; Lee, Melissa A.; Donnell, Nathaniel J.; Goode, Travis D.; Prosser, Rebecca A.; Cooper, Matthew A.

doi:10.1101/lm.040253.115

Cited by 16 publications

(11 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When BDNF activity is obstructed, major deficits in learning and memory are readily apparent [3–6], and these deficits can be prevented or even rescued by introducing BDNF [3–8]. Furthermore, BDNF has also been associated with hippocampal plasticity, a major neural correlate of learning and memory [9, 10].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: BNDF heterozygosity is associated with memory deficits and alterations in cortical and hippocampal EEG power

Geist

Dulka

Barnes

et al. 2017

Behavioural Brain Research

Self Cite

View full text Add to dashboard Cite

Brain derived neurotrophic factor (BDNF) plays a pivotal role in structural plasticity, learning, and memory. Electroencephalogram (EEG) spectral power in the cortex and hippocampus has also been correlated with learning and memory. In this study, we investigated the effect of globally reduced BDNF levels on learning behavior and EEG power via BDNF heterozygous (KO) rats. We employed several behavioral tests that are thought to depend on cortical and hippocampal plasticity to varying degrees: novel object recognition, a test that is reliant on a variety of cognitive systems; contextual fear, which is highly hippocampal-dependent; and cued fear, which has been shown to be amygdala-dependent. We also examined the effects of BDNF reduction on cortical and hippocampal EEG spectral power via chronically implanted electrodes in the motor cortex and dorsal hippocampus. We found that BDNF KO rats were impaired in novelty recognition and fear memory retention, while hippocampal EEG power was decreased in slow waves and increased in fast waves. Interestingly, our results, for the first time, show sexual dimorphism in each of our tests. These results support the hypothesis that BDNF drives both cognitive plasticity and coordinates EEG activity patterns, potentially serving as a link between the two.

show abstract

Section: Introductionmentioning

confidence: 99%

RETRACTED: BNDF heterozygosity is associated with memory deficits and alterations in cortical and hippocampal EEG power

Geist

Dulka

Barnes

et al. 2017

Behavioural Brain Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…One possibility is that increased NAS in susceptible mice is associated with a stronger memory of the defeat experience. This possibility is consistent with our previous finding that inhibition of the BDNF synthesis pathway in the BLA reduced defeat-induced social avoidance ( Dulka et al., 2016 ).…”

Section: Discussionsupporting

confidence: 93%

“…The ventromedial prefrontal cortex (vmPFC) also provides top-down inhibitory control of the NAc and amygdala, which promotes a resistant phenotype after social defeat stress ( Vialou et al., 2014 ). In a mouse model using a single day of acute social defeat, BDNF signaling in the basolateral amygdala (BLA) is necessary for acquisition of defeat-induced social avoidance ( Dulka et al., 2016 ). The development of the susceptible and resistant phenotypes is largely unknown, although the epigenetic changes that underlie stress vulnerability may be linked to environmental influences during pre-natal and post-natal development, including the establishment of early dominance hierarchies ( Peaston and Whitelaw, 2006 , Wong et al., 2005 ).…”

Section: Introductionmentioning

confidence: 99%

Metabolomics reveals distinct neurochemical profiles associated with stress resilience

Dulka

Bourdon

Clinard

et al. 2017

Neurobiology of Stress

Self Cite

View full text Add to dashboard Cite

Acute social defeat represents a naturalistic form of conditioned fear and is an excellent model in which to investigate the biological basis of stress resilience. While there is growing interest in identifying biomarkers of stress resilience, until recently, it has not been feasible to associate levels of large numbers of neurochemicals and metabolites to stress-related phenotypes. The objective of the present study was to use an untargeted metabolomics approach to identify known and unknown neurochemicals in select brain regions that distinguish susceptible and resistant individuals in two rodent models of acute social defeat. In the first experiment, male mice were first phenotyped as resistant or susceptible. Then, mice were subjected to acute social defeat, and tissues were immediately collected from the ventromedial prefrontal cortex (vmPFC), basolateral/central amygdala (BLA/CeA), nucleus accumbens (NAc), and dorsal hippocampus (dHPC). Ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS) was used for the detection of water-soluble neurochemicals. In the second experiment, male Syrian hamsters were paired in daily agonistic encounters for 2 weeks, during which they formed stable dominant-subordinate relationships. Then, 24 h after the last dominance encounter, animals were exposed to acute social defeat stress. Immediately after social defeat, tissue was collected from the vmPFC, BLA/CeA, NAc, and dHPC for analysis using UPLC-HRMS. Although no single biomarker characterized stress-related phenotypes in both species, commonalities were found. For instance, in both model systems, animals resistant to social defeat stress also show increased concentration of molecules to protect against oxidative stress in the NAc and vmPFC. Additionally, in both mice and hamsters, unidentified spectral features were preliminarily annotated as potential targets for future experiments. Overall, these findings suggest that a metabolomics approach can identify functional groups of neurochemicals that may serve as novel targets for the diagnosis, treatment, or prevention of stress-related mental illness.

show abstract

“…In contrast, decreased BDNF in the hippocampus is implied to participate in social-defeat-induced anxiety-like symptoms [21,96]. For the amygdala, BDNF levels have been reported to be elevated after the social defeat paradigm, which is associated with social avoidance and submission learning in mice [97,98]. For the mPFC, although some research works have stated that social defeat stress upregulates BDNF expression [99], there is still a subset of studies that did not observe significant alterations [21,100] or proposed the opposite, downregulation effect on BDNF expression [101,102].…”

Section: Repeated Social Defeat Stressmentioning

confidence: 99%

The Relationships Between Stress, Mental Disorders, and Epigenetic Regulation of BDNF

Zhang

Wang

Sun

2020

IJMS

View full text Add to dashboard Cite

Brain-derived neurotrophic factor (BDNF), a critical member of the neurotrophic family, plays an important role in multiple stress-related mental disorders. Although alterations in BDNF in multiple brain regions of individuals experiencing stress have been demonstrated in previous studies, it appears that a set of elements are involved in the complex regulation. In this review, we summarize the specific brain regions with altered BDNF expression during stress exposure. How various environmental factors, including both physical and psychological stress, affect the expression of BDNF in specific brain regions are further summarized. Moreover, epigenetic regulation of BDNF, including DNA methylation, histone modification, and noncoding RNA, in response to diverse types of stress, as well as sex differences in the sensitivity of BDNF to the stress response, is also summarized. Clarification of the underlying role of BDNF in the stress process will promote our understanding of the pathology of stress-linked mental disorders and provide a potent target for the future treatment of stress-related illness.

show abstract

Proteolytic cleavage of proBDNF into mature BDNF in the basolateral amygdala is necessary for defeat-induced social avoidance

Cited by 16 publications

References 50 publications

RETRACTED: BNDF heterozygosity is associated with memory deficits and alterations in cortical and hippocampal EEG power

RETRACTED: BNDF heterozygosity is associated with memory deficits and alterations in cortical and hippocampal EEG power

Metabolomics reveals distinct neurochemical profiles associated with stress resilience

The Relationships Between Stress, Mental Disorders, and Epigenetic Regulation of BDNF

Contact Info

Product

Resources

About