Brain-derived neurotrophic factor and epilepsy: a systematic review

Iughetti, Lorenzo; Lucaccioni, Laura; Fugetto, Francesco; Predieri, Barbara; Berardi, Alberto; Ferrari, Fabrizio

doi:10.1016/j.npep.2018.09.005

Cited by 100 publications

(69 citation statements)

References 56 publications

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“…However, epilepsy did reprogram the 738 anxiety/BDNF relationship. BDNF is involved in numerous functions and phenotypic traits, in 739 particular, stress (Murinova et al, 2017) and epilepsy (Iughetti et al, 2018). Although there 740 31 exists a linear relationship between anxiety and serum BNDF, the relationship is shifted towards 741 larger anxiety value in Pilo mice, while the slope remains mostly unaffected.…”

Section: Discussion 666mentioning

confidence: 99%

Effects of single cage housing on stress, cognitive and seizure parameters in the rat and mouse pilocarpine models of epilepsy

Manouze

Ghestem

Poillerat

et al. 2017

Preprint

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Many experimental approaches require housing rodents in individual cages, including in epilepsy research. However, rats and mice are social animals; and individual housing constitutes a stressful situation. The goal of the present study was to determine the effects of individual housing as compared to conditions maintaining social contact on stress markers and epilepsy. Control male mice socially housed during pretest and then transferred to individual cages for six weeks displayed anhedonia, increased anxiety and biological markers of stress as compared to pretest values or mice kept socially housed during six weeks. Pilocarpine-treated mice housed together showed increased levels of anhedonia, anxiety and stress markers as well as decreased cognitive performance as compared to the control group. The differences were more significant in pilocarpine-treated mice housed individually. Anxiety correlated linearly with cognitive performance and stress markers independently of the experimental conditions. In the male rat pilocarpine model, seizures were sixteen times more frequent in singly housed animals as compared to animals kept in pairs. Daily interactions with an experimenter in otherwise singly housed animals was sufficient to produce results identical to those found in animals kept in pairs. We propose that social isolation produces a severe phenotype in terms of stress and seizure frequency as compared to animals maintaining social contact (at least in these two models), a factor that needs to be taken into account for data interpretation, in particular for preclinical studies.Significance StatementMany experimental approaches require housing rodents in individual cages, a stressful condition for social animals, even in an enriched environment context. Using the pilocarpine model of epilepsy in rats and mice, we report that singly housing animals develop a more severe phenotype in terms of stress and epilepsy as compared to animals maintaining social contact. We propose that social isolation adds a degree of complexity for the interpretation of data, which may be particularly relevant for preclinical studies.

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Section: Discussion 666mentioning

confidence: 99%

Effects of single cage housing on stress, cognitive and seizure parameters in the rat and mouse pilocarpine models of epilepsy

Manouze

Ghestem

Poillerat

et al. 2017

Preprint

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“…For neurons, genes only differentially expressed in the ILH comprise pathways within various inflammatory responses and epilepsy-relevant genes like Mir132 (53) and Drd1 (54) ( Table 5 and Supplementary Table, sheet 21). In glia, genes upregulated in the ILH but not in the CLH include several interferon-and interleukin-associated genes like Ifit3, Iigp1, Ifi204, and Il4ra, other inflammatory genes previously associated with epilepsy like Ptgs2 (Cox2) (55), and epilepsy-related genes like Bdnf (56) and Mir132 (53) ( Table 6 and Supplementary Table, sheet 24). Downregulated genes in glia involve, among others, Grm3, a gene encoding for the metabotropic glutamate receptor 3, previously shown to be downregulated in experimental and human mTLE (57).…”

Section: Potential Upstream Targets Of Hippocampal Sclerosis and Epilmentioning

confidence: 99%

Differential Glial Activation in Early Epileptogenesis—Insights From Cell-Specific Analysis of DNA Methylation and Gene Expression in the Contralateral Hippocampus

et al. 2020

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Background and Aims: Morphological changes in mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) are well-characterized. Yet, it remains elusive whether these are a consequence of seizures or originate from a hitherto unknown underlying pathology. We recently published data on changes in gene expression and DNA methylation in the ipsilateral hippocampus (ILH) using the intracortical kainate mouse model of mTLE-HS. In order to explore the effects of epileptic activity alone and also to further disentangle what triggers morphological alterations, we investigated glial and neuronal changes in gene expression and DNA methylation in the contralateral hippocampus (CLH). Methods: The intracortical kainic acid mouse model of mTLE-HS was used to elicit status epilepticus. Hippocampi contralateral to the injection site from eight kainate-injected and eight sham mice were extracted and shock frozen at 24 h post-injection. Glial and neuronal nuclei were sorted by flow cytometry. Alterations in gene expression and DNA methylation were assessed using reduced representation bisulfite sequencing and RNA sequencing. The R package edgeR was used for statistical analysis. Results: The CLH featured substantial, mostly cell-specific changes in both gene expression and DNA methylation in glia and neurons. While changes in gene expression overlapped to a great degree between CLH and ILH, alterations in DNA methylation did not. In the CLH, we found a significantly lower number of glial genes up- and downregulated compared to previous results from the ILH. Furthermore, several genes and pathways potentially involved in anti-epileptogenic effects were upregulated in the CLH. By comparing gene expression data from the CLH to previous results from the ILH (featuring hippocampal sclerosis), we derive potential upstream targets for epileptogenesis, including glial Cox2 and Cxcl10 . Conclusion: Despite the absence of morphological changes, the CLH displays substantial changes in gene expression and DNA methylation. We find that gene expression changes related to potential anti-epileptogenic effects seem to dominate compared to the pro-epileptogenic effects in the CLH and speculate whether this imbalance contributes to prevent morphological alterations like neuronal death and reactive gliosis.

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“…Serum levels of BDNF are altered in children with intellectual disability and ASD and also in children with other neurodevelopmental disorders, even in the absence of ASD 52 . Other disorders in which abnormalities of BDNF were described are epilepsy 53 , Parkinson disease 54 , and Alzheimer disease 55 . Nutritional quality and physical exercise 56 have also been linked to altered BDNF levels in patients with ASD.…”

Section: Discussionmentioning

confidence: 99%

Assessment of BDNF serum levels as a diagnostic marker in children with autism spectrum disorder

Barbosa

Pratesi

Paz

et al. 2020

Sci Rep

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There has been a significant increase in autism spectrum disorder (ASD) in the last decades that cannot be exclusively attributed to better diagnosis and an increase in the communication of new cases. Patients with ASD often show dysregulation of proteins associated with synaptic plasticity, notably brain-derived neurotrophic factor (BDNF). The objective of the present study was to analyze BDNF serum concentration levels in children with classic forms autism and a healthy control group to determine if there is a correlation between ASD and BDNF serum levels. Forty-nine children with severe classic form of autism, and 37 healthy children were enrolled in the study. Blood samples, from both patients and controls, were collected and BNDF levels from both groups were analyzed. The average BDNF serum concentration level was statistically higher for children with ASD (P < 0.000) compared to the control group. There is little doubt that BDNF plays a role in the pathophysiology of ASD development and evolution, but its brain levels may fluctuate depending on several known and unknown factors. The critical question is not if BDNF levels can be considered a prognostic or diagnostic marker of ASD, but to determine its role in the onset and progression of this disorder.

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Brain-derived neurotrophic factor and epilepsy: a systematic review

Cited by 100 publications

References 56 publications

Effects of single cage housing on stress, cognitive and seizure parameters in the rat and mouse pilocarpine models of epilepsy

Effects of single cage housing on stress, cognitive and seizure parameters in the rat and mouse pilocarpine models of epilepsy

Differential Glial Activation in Early Epileptogenesis—Insights From Cell-Specific Analysis of DNA Methylation and Gene Expression in the Contralateral Hippocampus

Assessment of BDNF serum levels as a diagnostic marker in children with autism spectrum disorder

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