Brain-derived neurotrophic factor (BDNF) overexpression in the forebrain results in learning and memory impairments

Cunha, Carla; Angelucci, Andrea; D'Antoni, Angela; Döbrössy, Máté; Dunnett, Stephen B.; Berardi, Nicoletta; Brambilla, Riccardo

doi:10.1016/j.nbd.2008.11.004

Cited by 106 publications

(69 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with our results, diminished working memory performance in aged female rats positively correlated with high BDNF levels in the PFC (Bimonte et al 2003). Similarly, in male BDNF-tg mice, mild cognitive deficits were reported in an eight-arm radial maze protocol, in which each arm was baited and mice were allowed to move freely through them (Cunha et al 2009). The paradigm adopted by Cunha and colleagues, however, might suffer from possible response patterns, because guillotine doors were not used and mice might choose the correct arms by response habits or memory for previous choices (Olton 1987).…”

Section: Discussionsupporting

confidence: 87%

“…Similarly, genetic BDNF disruption in mice showed sex differences, at least for parameters such as locomotor activity, stress reactivity, and anxiety-and depression-like behaviors (Monteggia et al 2007;Autry et al 2009). To date, all previous studies investigating the effects of increased BDNF genetic modifications have used only males or have overlooked the distinct behavioral consequences in females (Chen et al 2006;Govindarajan et al 2006;Cunha et al 2009;Yu et al 2009;Soliman et al 2010). It is important to consistently and separately study both sexes.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, genetic manipulations that increase BDNF expression in mice similarly increased anxiety-like behaviors, but decreased immobility in the forced swim test (Govindarajan et al 2006). Moreover, BDNF overexpression in mice resulted in memory impairments on passive avoidance, eight-arm radial maze, and Morris watermaze tests (Croll et al 1999;Cunha et al 2009). Thus, current evidence indicates that genetic mutations that both decrease and increase BDNF levels might have detrimental effects.…”

mentioning

confidence: 99%

“…Moreover, different levels of specific BDNF isoforms have been correlated with schizophrenia and its cognitive impairments (Carlino et al 2010). BDNF-tg male mice show a significant increase in total BDNF levels without apparent changes in the pro-BDNF protein (Cunha et al 2009). To investigate which specific BDNF isoforms are altered in the BDNF-tg mice, we assayed the different BDNF isoforms in the PFC of our mice.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Working memory deficits, increased anxiety-like traits, and seizure susceptibility in BDNF overexpressing mice

et al. 2011

View full text Add to dashboard Cite

BDNF regulates components of cognitive processes and has been implicated in psychiatric disorders. Here we report that genetic overexpression of the BDNF mature isoform (BDNF-tg) in female mice impaired working memory functions while sparing components of fear conditioning. BDNF-tg mice also displayed reduced breeding efficiency, higher anxiety-like scores, high self-grooming, impaired prepulse inhibition, and higher susceptibility to seizures when placed in a new empty cage, as compared with wild-type (WT) littermate controls. Control measures of general health, locomotor activity, motor coordination, depression-related behaviors, and sociability did not differ between genotypes. The present findings, indicating detrimental effects of life-long increased BDNF in mice, may inform human studies evaluating the role of BDNF functional genetic variations on cognitive abilities and vulnerability to psychiatric disorders.Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors and is most highly concentrated in the hippocampus and frontal cortex (Baquet et al. 2004). BDNF has been implicated in a number of processes includ-

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Working memory deficits, increased anxiety-like traits, and seizure susceptibility in BDNF overexpressing mice

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Cunha et al showed that moderate BDNF overexpression in rats may lead to impaired learning in spatial and instrumental memory tasks. Authors suggest that the excess of mature BDNF may lead to inhibition of synaptic circuitry involved in learning [38].…”

Section: Brain-derived Neurotrophic Factor Val66met Polymorphism In Cmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor Val66Met Polymorphism in Contex of Executive Functions and Working Memory in Obese Patients

Bieliaski¹,

Lesiewska²,

Jaracz³

et al. 2018

Neuropsychiatry

View full text Add to dashboard Cite

Neurothrophins are crucial in the regulation of many processes, such as nerve cells development and neuroplasticity and brain-derived neurothrophic factor (BDNF) is the major one. Researchers still scrutinize the role of BDNF Val66Met polymorphism in eating disorders and cognition, however, literature present inconsistent findings regarding this topic. Most of all, the exact mechanism of how exactly BDNF influences cognitive functioning in obesity is unknown. In our study, we try to elucidate the association of BDNF Val66Met polymorphism with executive functions and working memory on large obese population. 375 obese patients underwent biometric analyses and neuropsychological assessment. The Wisconsin Card Sorting Test (WCST) was used to assess cognitive functions. Genetic polymorphism in BDNF was evaluated in peripheral blood samples.Results indicated that both BDNF Val66Met polymorphism and gender showed significant correlations with BMI, WCST_P and WCST_CLR. Females showed higher BMI values than men,, however males scored higher in WSCT_P and WSCT_CLR. Val/Val carriers presented worse results of WCST and BMI. Kendall's partial rank correlation tests determined that both genotype and BMI showed significant correlations with WCST_CLR, WCST_CC and WCST_1st, in which BMI correlation was stronger. Analysis of mild and morbid obesity showed, that severe obese younger subjects presented worse WCST_P, WCST_NP, and WCST_CLR. Significant interaction effects for WCST parameters were found for gender, age, BMI and BDNF Val66Met. Importantly, in this study none Met/Met carriers were observed.The Val66Met BDNF polymorphism indirectly influenced the poorer cognitive functioning observed in the obese subpopulation with Val/Val genotype, rather than Val/Met genotype. A higher BMI was associated with the Val allele, suggesting that obesity may have deteriorated the activity of the prefrontal cortex. According to results, BDNF Val66Met polymorphism seems to contribute to greater obesity in our study. It is greater BMI, rather than genotype, which caused worse executive functioning and working memory. KeywordsVal66Met BDNF, Neurothrophins, Obesity Neuropsychiatry (London) (2018) 8(1) 112Research Maciej Bieliński the worse scores in WCST, and how BDNF Val66Met influences the severity of obesity. Materials and Methods ParticipantsA total of 375 adult Caucasian patients of Polish nationality were enrolled in this study, including 233 women and 142 men, after excluding secondary reasons of obesity. The mean age of all participants was 54 (range, 20-76) years old; the mean age for women was 52 (20-75) years old, and for men 56 (42-67) years old. The exclusion criteria were individuals with a severe somatic or psychiatric disorder included in the Diagnostic

show abstract

Methionine increases BDNF DNA methylation and improves memory in epilepsy

Parrish

Buckingham

Mascia

et al. 2015

Ann Clin Transl Neurol

View full text Add to dashboard Cite

ObjectiveTemporal lobe epilepsy (TLE) patients exhibit signs of memory impairments even when seizures are pharmacologically controlled. Surprisingly, the underlying molecular mechanisms involved in TLE-associated memory impairments remain elusive. Memory consolidation requires epigenetic transcriptional regulation of genes in the hippocampus; therefore, we aimed to determine how epigenetic DNA methylation mechanisms affect learning-induced transcription of memory-permissive genes in the epileptic hippocampus.MethodsUsing the kainate rodent model of TLE and focusing on the brain-derived neurotrophic factor (Bdnf) gene as a candidate of DNA methylation-mediated transcription, we analyzed DNA methylation levels in epileptic rats following learning. After detection of aberrant DNA methylation at the Bdnf gene, we investigated functional effects of altered DNA methylation on hippocampus-dependent memory formation in our TLE rodent model.ResultsWe found that behaviorally driven BdnfDNA methylation was associated with hippocampus-dependent memory deficits. Bisulfite sequencing revealed that decreased BdnfDNA methylation levels strongly correlated with abnormally high levels of BdnfmRNA in the epileptic hippocampus during memory consolidation. Methyl supplementation via methionine (Met) increased BdnfDNA methylation and reduced BdnfmRNA levels in the epileptic hippocampus during memory consolidation. Met administration reduced interictal spike activity, increased theta rhythm power, and reversed memory deficits in epileptic animals. The rescue effect of Met treatment on learning-induced BdnfDNA methylation, Bdnf gene expression, and hippocampus-dependent memory, were attenuated by DNA methyltransferase blockade.InterpretationOur findings suggest that manipulation of DNA methylation in the epileptic hippocampus should be considered as a viable treatment option to ameliorate memory impairments associated with TLE.

show abstract

Brain-derived neurotrophic factor (BDNF) overexpression in the forebrain results in learning and memory impairments

Cited by 106 publications

References 79 publications

Working memory deficits, increased anxiety-like traits, and seizure susceptibility in BDNF overexpressing mice

Working memory deficits, increased anxiety-like traits, and seizure susceptibility in BDNF overexpressing mice

Brain-Derived Neurotrophic Factor Val66Met Polymorphism in Contex of Executive Functions and Working Memory in Obese Patients

Methionine increases BDNF DNA methylation and improves memory in epilepsy

Contact Info

Product

Resources

About