BDNF Val66Met genotype determines hippocampus-dependent behavior via sensitivity to glucocorticoid signaling

Notaras, Michael; Hill, Rachel Anne; Gogos, Joseph A.; Buuse, Maarten van den

doi:10.1038/mp.2015.152

Cited by 52 publications

(50 citation statements)

References 14 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This analysis strategy is consistent with clinical research given the potentially small effect sizes generated by the Val66Met polymorphism, 34 as well as our previous report utilizing this mouse line. 30 …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

BDNF Val66Met Genotype Interacts With a History of Simulated Stress Exposure to Regulate Sensorimotor Gating and Startle Reactivity

Notaras

Hill

Gogos

et al. 2016

SCHBUL

View full text Add to dashboard Cite

Reduced expression of Brain-Derived Neurotrophic Factor (BDNF) has been implicated in the pathophysiology of schizophrenia. The BDNF Val66Met polymorphism, which results in deficient activity-dependent secretion of BDNF, is associated with clinical features of schizophrenia. We investigated the effect of this polymorphism on Prepulse Inhibition (PPI), a translational model of sensorimotor gating which is disrupted in schizophrenia. We utilized humanized BDNF Val66Met (hBDNF Val66Met) mice which have been modified to carry the Val66Met polymorphism, as well as express humanized BDNF in vivo. We also studied the longterm effect of chronic corticosterone (CORT) exposure in these animals as a model of history of stress. PPI was assessed at 30 ms and 100 ms interstimulus intervals (ISI). Analysis of PPI at the commonly used 100 ms ISI identified that, irrespective of CORT treatment, the hBDNF

show abstract

Section: Discussionmentioning

confidence: 99%

“…30 Treatment occurred between weeks 6 to 9, a period we have previously established to mimic late adolescence/early adulthood 31 that is also commonly associated with the emergence of the psychosis prodome. The CORT solution was changed every 3 days over the treatment period.…”

Section: Chronic Cort Protocolmentioning

confidence: 99%

BDNF Val66Met Genotype Interacts With a History of Simulated Stress Exposure to Regulate Sensorimotor Gating and Startle Reactivity

Notaras

Hill

Gogos

et al. 2016

SCHBUL

View full text Add to dashboard Cite

show abstract

“…Environmental stress is considered as a pathogenetic element of a high importance in psychiatry (De Kloet et al., 2005, McEwen and Stellar, 1993, McEwen, 2008, Millan et al., 2012, Peyrot et al., 2015). (3) The interaction between the genome and the environment has a strong context limiting/permitting component (Notaras et al., 2016). Mechanisms that evolved over millions of years to protect individuals from a life-threatening environment have become maladaptive in respect to contemporary socio-cultural demands (Del Giudice, 2016, Ellis and Del Giudice, 2014, First and Wakefield, 2013).…”

Section: Nosological Entity Problem In Psychiatrymentioning

confidence: 99%

Animal models in psychiatric research: The RDoC system as a new framework for endophenotype-oriented translational neuroscience

Anderzhanova

Kirmeier

Wotjak

2017

Neurobiology of Stress

View full text Add to dashboard Cite

The recently proposed Research Domain Criteria (RDoC) system defines psychopathologies as phenomena of multilevel neurobiological existence and assigns them to 5 behavioural domains characterizing a brain in action. We performed an analysis on this contemporary concept of psychopathologies in respect to a brain phylogeny and biological substrates of psychiatric diseases. We found that the RDoC system uses biological determinism to explain the pathogenesis of distinct psychiatric symptoms and emphasises exploration of endophenotypes but not of complex diseases. Therefore, as a possible framework for experimental studies it allows one to evade a major challenge of translational studies of strict disease-to-model correspondence. The system conforms with the concept of a normality and pathology continuum, therefore, supports basic studies. The units of analysis of the RDoC system appear as a novel matrix for model validation. The general regulation and arousal, positive valence, negative valence, and social interactions behavioural domains of the RDoC system show basic construct, network, and phenomenological homologies between human and experimental animals. The nature and complexity of the cognitive behavioural domain of the RDoC system deserve further clarification. These homologies in the 4 domains justifies the validity, reliably and translatability of animal models appearing as endophenotypes of the negative and positive affect, social interaction and general regulation and arousal systems’ dysfunction.

show abstract

“…These findings suggest that BDNF met/met mice perform better on the trace fearconditioning test because they are sensitized to the stressful effects (ie, generalized anxiety and fear) of this paradigm. Interestingly, Notaras et al52 recently reported that adult knock-in mice expressing the human BDNF met/met polymorphism freeze less than BDNF val/val mice in a contextual fear-conditioning paradigm. However, when these mice were chronically exposed to corticosterone during adolescence, BDNF met/met mice performed better than BDNF val/val mice.Future studies should investigate if our BDNF met/met mice have abnormalities in the hypothalamic-pituitary-adrenal axis that could explain their enhanced ability to form memories of fear-related events.…”

mentioning

confidence: 99%

The brain‐derived neurotrophic factor VAL68MET polymorphism modulates how developmental ethanol exposure impacts the hippocampus

Bird

Baculis

Mayfield

et al. 2018

Genes Brain and Behavior

View full text Add to dashboard Cite

Prenatal exposure to alcohol causes a wide range of deficits known as fetal alcohol spectrum disorders (FASDs). Many factors determine vulnerability to developmental alcohol exposure including timing and pattern of exposure, nutrition and genetics. Here, we characterized how a prevalent single nucleotide polymorphism in the human brain-derived neurotrophic factor (BDNF) gene (val66met) modulates FASDs severity. This polymorphism disrupts BDNF's intracellular trafficking and activity-dependent secretion, and has been linked to increased incidence of neuropsychiatric disorders such as depression and anxiety. We hypothesized that developmental ethanol (EtOH) exposure more severely affects mice carrying this polymorphism. We used transgenic mice homozygous for either valine (BDNF ) or methionine (BDNF ) in residue 68, equivalent to residue 66 in humans. To model EtOH exposure during the second and third trimesters of human pregnancy, we exposed mice to EtOH in vapor chambers during gestational days 12 to 19 and postnatal days 2 to 9. We found that EtOH exposure reduces cell layer volume in the dentate gyrus and the CA1 hippocampal regions of BDNF but not BDNF mice during the juvenile period (postnatal day 15). During adulthood, EtOH exposure reduced anxiety-like behavior and disrupted trace fear conditioning in BDNF mice, with most effects observed in males. EtOH exposure reduced adult neurogenesis only in the ventral hippocampus of BDNF male mice. These studies show that the BDNF val66met polymorphism modulates, in a complex manner, the effects of developmental EtOH exposure, and identify a novel genetic risk factor that may regulate FASDs severity in humans.

show abstract

BDNF Val66Met genotype determines hippocampus-dependent behavior via sensitivity to glucocorticoid signaling

Cited by 52 publications

References 14 publications

BDNF Val66Met Genotype Interacts With a History of Simulated Stress Exposure to Regulate Sensorimotor Gating and Startle Reactivity

BDNF Val66Met Genotype Interacts With a History of Simulated Stress Exposure to Regulate Sensorimotor Gating and Startle Reactivity

Animal models in psychiatric research: The RDoC system as a new framework for endophenotype-oriented translational neuroscience

The brain‐derived neurotrophic factor VAL68MET polymorphism modulates how developmental ethanol exposure impacts the hippocampus

Contact Info

Product

Resources

About