Brain-derived neurotrophic factor heterozygous mutant rats show selective cognitive changes and vulnerability to chronic corticosterone treatment

Gururajan, Anand; Hill, Rachel Anne; Buuse, Maarten van den

doi:10.1016/j.neuroscience.2014.10.009

Cited by 30 publications

(26 citation statements)

References 54 publications

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“…According to our results, male KO rats were able to discriminate the novel object from the familiar object, which matches previous literature [48]. However, female KO rats were not able to discriminate successfully, indicating a sex difference in NOR behavior.…”

Section: Discussionsupporting

confidence: 91%

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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

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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.

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Section: Discussionsupporting

confidence: 91%

“…It is important to mention that the present study found behavioral alterations in BDNF KO rats in the NOR paradigm, which has never before been reported [48, 50, 51]. Specifically, the WT animals increased total object exploration during the test phase, but the KO animals did not.…”

Section: Discussionsupporting

confidence: 56%

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

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“…Cognitive impairments are often seen in MDD patients 59 and reduced BDNF levels have been implicated with impaired spatial short-term memory in rats. 60 Similarly, spatial working memory was also impaired in response to stress exposure in a preclinical MDD model. 43 We found that spatial working memory was intact in the BDNF +/− group compared to WT rats as examined in the SAB test.…”

Section: Discussionmentioning

confidence: 96%

BDNF^+/− rats exhibit depressive phenotype and altered expression of genes relevant in mood disorders

Martis

Wiborg

Holmes

et al. 2019

Genes Brain and Behavior

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Major depressive disorder (MDD) is a leading contributor to the global burden of disease. However, the causal relationship of risk factors, such as genetic predisposition or experience of augmented stress, remain unknown. Numerous studies in humans and rodents have implicated brain‐derived neurotrophic factor (BDNF) in MDD pathology, as a genetic risk factor and a factor regulated by stress. Until now, the majority of preclinical studies have employed genetically modified mice as their model of choice. However, mice display a limited behavioural repertoire and lack expression of circulating BDNF, which is present in rats and humans. Therefore, heterozygous BDNF (BDNF+/−) rats were tested for affective behaviours and accompanying expression of key genes associated with affective disorders in the brain. We found that BDNF+/− rats, which have reduced BDNF levels in brain and plasma, displayed symptoms of anhedonia, a core symptom of MDD, and anxiety‐like behaviour, but no behavioural despair or cognitive impairments. This was accompanied by changes in the expression of genes that are implicated in modulation of the stress response and affective disorders. Hence, glucocorticoid receptor, neuregulin 1 and disrupted‐in‐schizophrenia 1 gene expression were upregulated in the prefrontal cortex of BDFN+/− rats, whereas FK506 binding protein 5 levels were decreased in the hippocampus. We conclude that a reduction in BDNF levels alters expression of genes associated with affective disorders, which may contribute to the development of depressive‐like symptoms.

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“…BDNF is a member of the neurotrophic family, which promotes neuronal survival, axonal growth, and neuroprotection, and has been recognized as a potential therapeutic agent for different neurodegenerative diseases [30,31,32]. BDNF exerts neuroprotective effects mainly via binding to its high-affinity tropomyosin-receptor kinase B (TrkB) [33,34].…”

Section: Discussionmentioning

confidence: 99%

Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice

Huang

et al. 2018

IJMS

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Strokes are one of the leading causes of mortality and chronic morbidity in the world, yet with only limited successful interventions available at present. Our previous studies revealed the potential role of the glucocorticoid receptor (GR) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). In the present study, we investigate the effect of GR knockdown on acute ischemic brain injuries in a model of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in adult male CD1 mice. GR siRNAs and the negative control were administered via intracerebroventricular (i.c.v.) injection 48 h prior to MCAO. The cerebral infarction volume and neurobehavioral deficits were determined 48 h after MCAO. RT-qPCR was employed to assess the inflammation-related gene expression profiles in the brain before and after MCAO. Western Blotting was used to evaluate the expression levels of GR, the mineralocorticoid receptor (MR) and the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling. The siRNAs treatment decreased GR, but not MR, protein expression, and significantly enhanced expression levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in the brain. Of interest, GR knockdown suppressed BDNF/TrkB signaling in adult mice brains. Importantly, GR siRNA pretreatment significantly increased the infarction size and exacerbated the neurobehavioral deficits induced by MCAO in comparison to the control group. Thus, the present study demonstrates the important role of GR in the regulation of the inflammatory responses and neurotrophic BDNF/TrkB signaling pathway in acute ischemic brain injuries in adult mice, revealing a new insight into the pathogenesis and therapeutic potential in acute ischemic strokes.

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Brain-derived neurotrophic factor heterozygous mutant rats show selective cognitive changes and vulnerability to chronic corticosterone treatment

Cited by 30 publications

References 54 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

BDNF^+/− rats exhibit depressive phenotype and altered expression of genes relevant in mood disorders

Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice

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Brain-derived neurotrophic factor heterozygous mutant rats show selective cognitive changes and vulnerability to chronic corticosterone treatment

Cited by 30 publications

References 54 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

BDNF+/− rats exhibit depressive phenotype and altered expression of genes relevant in mood disorders

Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice

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BDNF^+/− rats exhibit depressive phenotype and altered expression of genes relevant in mood disorders