Increased expression of BDNF transcript with exon VI in hippocampi of patients with pharmaco-resistant temporal lobe epilepsy

Martínez-Levy, Gabriela Ariadna; Rocha, Luísa; Lubin, Farah D.; Alonso-Vanegas, Mario; Nani, Andrés; Buentello-García, Ricardo Masao; Pérez‐Molina, Rosario; Briones-Velasco, Magdalena; Recillas‐Targa, Félix; Pérez‐Molina, Amado; San-Juan, Daniel; Cienfuegos-Meza, Jesús; Cruz-Fuentes, Carlos S.

doi:10.1016/j.neuroscience.2015.11.046

Cited by 29 publications

(19 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such precocious maturation of inhibitory innervation might have detrimental consequences. BDNF expression is enhanced in the hippocampi of patients with TLE (Martinez-Levy et al, 2016) and excessive activation of TrkB by status epilepticus was shown to promote the development of TLE (Liu et al, 2013). BDNF-TrkB signaling has therefore been identified as an important therapeutic target in the prevention of epileptogenesis.…”

Section: Synaptic Connectivity Synaptogenesis: Gabaergic Synapse Formmentioning

confidence: 99%

Involvement of cortical fast-spiking parvalbumin-positive basket cells in epilepsy

Jiang

Lachance

Rossignol

2016

Progress in Brain Research

View full text Add to dashboard Cite

GABAergic interneurons of the parvalbumin-positive fast-spiking basket cells subtype (PV INs) are important regulators of cortical network excitability and of gamma oscillations, involved in signal processing and cognition. Impaired development or function of PV INs has been associated with epilepsy in various animal models of epilepsy, as well as in some genetic forms of epilepsy in humans. In this review, we provide an overview of some of the experimental data linking PV INs dysfunction with epilepsy, focusing on disorders of the specification, migration, maturation, synaptic function, or connectivity of PV INs. Furthermore, we reflect on the potential therapeutic use of cell-type specific stimulation of PV INs within active networks and on the transplantation of PV INs precursors in the treatment of epilepsy and its comorbidities.

show abstract

Section: Synaptic Connectivity Synaptogenesis: Gabaergic Synapse Formmentioning

confidence: 99%

Involvement of cortical fast-spiking parvalbumin-positive basket cells in epilepsy

Jiang

Lachance

Rossignol

2016

Progress in Brain Research

View full text Add to dashboard Cite

show abstract

“…CREB does not only influence transcription in the nucleus, but also leads to cell wide supply of protein and mRNA that can localize to the synapse when the synapse has been tagged, thereby permitting LTP [88, 89]. One transcript targeted by CREB is the brain derived neurotrophic factor (BDNF) [92], which has been associated to temporal lobe epilepsy in many cases [93] and may serve as a serum marker for epilepsy [94]. …”

Section: Crebmentioning

confidence: 99%

mTOR and MAPK: from localized translation control to epilepsy

Pernice¹,

Schieweck²,

Kiebler³

et al. 2016

BMC Neurosci

View full text Add to dashboard Cite

BackgroundEpilepsy is one of the most common neurological diseases characterized by excessive hyperexcitability of neurons. Molecular mechanisms of epilepsy are diverse and not really understood. All in common is the misregulation of proteins that determine excitability such as potassium and sodium channels as well as GABA receptors; which are all known as biomarkers for epilepsy. Two recently identified key pathways involve the kinases mechanistic target of rapamycin (mTOR) and mitogen-activated protein kinases (MAPK). Interestingly, mRNAs coding for those biomarkers are found to be localized at or near synapses indicating a local misregulation of synthesis and activity.ResultsResearch in the last decade indicates that RNA-binding proteins (RBPs) responsible for mRNA localization, stability and translation mediate local expression control. Among others, they are affected by mTOR and MAPK to guide expression of epileptic factors. These results suggest that mTOR/MAPK act on RBPs to regulate the fate of mRNAs, indicating a misregulation of protein expression at synapses in epilepsy.ConclusionWe propose that mTOR and MAPK regulate RBPs, thereby guiding the local expression of their target-mRNAs encoding for markers of epilepsy. Thus, misregulated mTOR/MAPK-RBP interplay may result in excessive local synthesis of ion channels and receptors thereby leading to hyperexcitability. Continuous stimulation of synapses further activates mTOR/MAPK pathway reinforcing their effect on RBP-mediated expression control establishing the basis for epilepsy. Here, we highlight findings showing the tight interplay between mTOR as well as MAPK with RBPs to control expression for epileptic biomarkers.

show abstract

“…Similarly, four isoforms of BDNF were found to be highly expressed in brain hippocampal tissue from adult epileptic patients compared to healthy controls, although the effect was not explained by changes in DNA methylation measured in the promoters of isoforms IV and VI [41] . It is to be noted that the association reported in the current study was located further upstream within the first intron of isoforms I, II, and III, based on the latest gene characterization [41,51]. Moreover, a recent family study investigating genome-wide DNA methylation in peripheral blood, based on 15 trios of parents and their offspring, where the child and one parent, but not the other, were affected by generalized genetic epilepsy, found evidence of neurotrophins involvement, particularly BDNF, which was both hyperand hypomethylated [52].…”

Section: Discussionmentioning

confidence: 94%

“…A study conducted on hippocampal tissue from 40 adult patients affected by mesial-temporal lobe epilepsy showed increased or decreased BDNF expression, compared to healthy individuals, depending on the region investigated and on the presence of psychiatric comorbidities [50]. Similarly, four isoforms of BDNF were found to be highly expressed in brain hippocampal tissue from adult epileptic patients compared to healthy controls, although the effect was not explained by changes in DNA methylation measured in the promoters of isoforms IV and VI [41] . It is to be noted that the association reported in the current study was located further upstream within the first intron of isoforms I, II, and III, based on the latest gene characterization [41,51].…”

Section: Discussionmentioning

confidence: 99%

“…For replication, we focused on five CpG sites: two that passed FDR correction in childhood and three that passed FDR correction in adolescence. As one of the CpG sites in adolescence was located in the gene BDNF, which is a key driver in neuronal growth and has been repeatedly linked to epilepsy [40,41], we expanded our search space to include all CpG sites annotated to BDNF (n = 73).…”

Section: Replication In the Generation R Studymentioning

confidence: 99%

See 1 more Smart Citation

Epigenome-wide association study of seizures in childhood and adolescence

et al. 2020

View full text Add to dashboard Cite

The occurrence of seizures in childhood is often associated with neurodevelopmental impairments and school underachievement. Common genetic variants associated with epilepsy have been identified and epigenetic mechanisms have also been suggested to play a role. In this study, we analyzed the association of genome-wide blood DNA methylation with the occurrence of seizures in~800 children from the Avon Longitudinal Study of Parents and Children, UK, at birth (cord blood), during childhood, and adolescence (peripheral blood). We also analyzed the association between the lifetime occurrence of any seizures before age 13 with blood DNA methylation levels. We sought replication of the findings in the Generation R Study and explored causality using Mendelian randomization, i.e., using genetic variants as proxies. The results showed five CpG sites which were associated cross-sectionally with seizures either in childhood or adolescence (1-5% absolute methylation difference at p FDR < 0.05), although the evidence of replication in an independent study was weak. One of these sites was located in the BDNF gene, which is highly expressed in the brain, and showed high correspondence with brain methylation levels. The Mendelian randomization analyses suggested that seizures might be causal for changes in methylation rather than vice-versa. In conclusion, we show a suggestive link between seizures and blood DNA methylation while at the same time exploring the limitations of conducting such study.

show abstract

Increased expression of BDNF transcript with exon VI in hippocampi of patients with pharmaco-resistant temporal lobe epilepsy

Cited by 29 publications

References 47 publications

Involvement of cortical fast-spiking parvalbumin-positive basket cells in epilepsy

Involvement of cortical fast-spiking parvalbumin-positive basket cells in epilepsy

mTOR and MAPK: from localized translation control to epilepsy

Epigenome-wide association study of seizures in childhood and adolescence

Contact Info

Product

Resources

About