Potential Role of Drebrin A, an F-Actin Binding Protein, in Reactive Synaptic Plasticity after Pilocarpine-Induced Seizures: Functional Implications in Epilepsy

Ferhat, Lotfi

doi:10.1155/2012/474351

Cited by 16 publications

(13 citation statements)

References 110 publications

(141 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results would therefore suggest that spectrin was truncated by calpain-1 activation in a relatively small subset of neurons, while PTEN would be degraded by calpain-2 activation in a much broader population of neurons. Our results also confirmed that drebrin, a neuron-specific F-actin binding protein, is also a calpain substrate, and is degraded following KA-induced seizure activity, a finding corroborating results indicating that drebrin levels were decreased in a pilocarpine model of epilepsy ( Ferhat, 2012 ). As the pattern of changes for drebrin was very similar to that for PTEN, we therefore suggest that drebrin was also cleaved by calpain-2 in the hours following seizure initiation.…”

Section: Discussionsupporting

confidence: 89%

Differential Activation of Calpain-1 and Calpain-2 following Kainate-Induced Seizure Activity in Rats and Mice

Seinfeld

Baudry

et al. 2016

eneuro

View full text Add to dashboard Cite

Visual AbstractSystemic injection of kainate produces repetitive seizure activity in both rats and mice.It also results in short-term synaptic modifications as well as delayed neurodegeneration. The signaling cascades involved in both short-term and delayed responses are not clearly defined. The calcium-dependent protease calpain is activated in various brain structures following systemic kainate injection, although the precise involvement of the two major brain calpain isoforms, calpain-1 and calpain-2, remains to be defined. It has recently been reported that calpain-1 and calpain-2 play opposite roles in NMDA receptor-mediated neuroprotection or neurode- Significance StatementSeizure activity results in both short-term and long-term alterations in the structure and organization of neurons in hippocampus. While the activation of calpain has been well documented following kainic acid (KA)-induced seizures, there is no information regarding the roles of the two major calpain isoforms in the brain, calpain-1 and calpain-2, in the consequences of seizures. Here we report the surprising findings that, while calpain-2 is rapidly activated in all pyramidal cells of CA1 and CA3, calpain-1 activation is restricted to a small population of interneurons following systemic KA injection. Furthermore, KA-induced neurodegeneration in CA1 is exacerbated in calpain-1 knock-out mice, further supporting the notion that calpain-1 is neuroprotective and calpain-2 is neurodegenerative. New ResearchJuly/August 2016, 3(4) e0088-15.2016 1-12 generation, with calpain-1 being neuroprotective and calpain-2 being neurodegenerative. In the present study, we determined the activation pattern of calpain-1 and calpain-2 by analyzing changes in levels of different calpain substrates, including spectrin, drebrin, and PTEN (phosphatase and tensin homolog; a specific calpain-2 substrate) in both rats, and wild-type and calpain-1 knock-out mice. The results indicate that, while calpain-2 is rapidly activated in pyramidal cells throughout CA1 and CA3, rapid calpain-1 activation is restricted to parvalbumin-positive and to a lesser extent CCKpositive, but not somatostatin-positive, interneurons. In addition, calpain-1 knock-out mice exhibit increased long-term neurodegeneration in CA1, reinforcing the notion that calpain-1 activation is neuroprotective.

show abstract

Section: Discussionsupporting

confidence: 89%

Differential Activation of Calpain-1 and Calpain-2 following Kainate-Induced Seizure Activity in Rats and Mice

Seinfeld

Baudry

et al. 2016

eneuro

View full text Add to dashboard Cite

show abstract

“…Accumulating evidence suggests a link between actin remodeling and complex neurological disorders [Kojima and Shirao, ; Ivanov et al, ]. Cofilin upregulation followed by the translocation of drebrin A from DS was proposed to be part of a pathological pathway relevant to Alzheimer's disease (AD), Down syndrome, and epilepsy [Kojima and Shirao, ; Ferhat, ]. This pathway, which was suggested to lead to spine shrinkage and the impairment of higher order brain function, can be a potential therapeutical target for complex brain disorders [Zhou et al, ; Cho et al, ].…”

Section: Introductionmentioning

confidence: 99%

Drebrin inhibits cofilin‐induced severing of F‐actin

Grintsevich

Reisler

2014

Cytoskeleton

View full text Add to dashboard Cite

Molecular cross-talk between neuronal drebrin A and cofilin is believed to be a part of the activity-dependent cytoskeleton-modulating pathway in dendritic spines. Impairments in this pathway are implicated also in synaptic dysfunction in Alzheimer’s disease, Down syndrome, epilepsy, and normal aging. However, up to now the molecular interplay between cofilin and drebrin has not been elucidated. TIRF microscopy and solution experiments revealed that full length drebrin A or its actin binding core (Drb1-300) inhibits, but do not abolish cofilin-induced severing of actin filaments. Cosedimentation experiments showed that F-actin can be fully occupied with combination of these two proteins. The dependence of cofilin binding on fractional saturation of actin filaments with drebrin suggests direct competition between these two proteins for F-actin binding. This implies that cofilin and drebrin can either overcome or reverse the allosteric changes in F-actin induced by the competitor’s binding. The ability of cofilin to displace drebrin from actin filaments is pH dependent and is facilitated at acidic pH (6.8). Pre-steady state kinetic experiments reveal that both binding and dissociation of drebrin to/from actin filaments is faster than that reported for cooperative binding of cofilin. We found, that drebrin displacement by cofilin is greatly inhibited when actin severing is abolished, which might be linked to the cooperativity of drebrin binding to actin filaments. Our results contribute to molecular understanding of the competitive interactions of drebrin and cofilin with actin filaments.

show abstract

“…Unfortunately, the detailed molecular mechanism of TLE is still unclear. Recent experimental evidence demonstrated that abnormal synaptic plasticity, including structural aberrations in dendrites of neurons, mossy fiber sprouts (MFS), and formation of anomalous excitatory loop in hippocampus are involved in pathology of TLE (Epsztein et al, 2005;Fang et al, 2011;Ferhat, 2012;Lukasiuk and Pitkanen, 2012). The unusual neural networks may cause abnormal discharge in the brain, which leads to recurrent seizures and long-time maintenance (Fernandez-Torre, 2002).…”

Section: Introductionmentioning

confidence: 99%

Decreased expression of Gab2 in patients with temporal lobe epilepsy and pilocarpine-induced rat model

Zhan

Chen

et al. 2013

Synapse

View full text Add to dashboard Cite

Growth factor receptor bound protein-2 associated binding protein-2 (Gab2) is widely expressed in the central nervous system, and participates in multiple signaling pathways. Recent studies showed that Gab2 was involved in the pathogenesis of Alzheimer's disease (AD). Gab2 reduces tau phosphorylation levels and is associated with cellular apoptosis and differentiation. However, whether Gab2 was also involved in the pathogenesis of epilepsy, remains unknown. This study aimed to investigate the expression pattern of Gab2 protein in brains with temporal lobe epilepsy (TLE) and in pilocarpine-induced rat model of TLE. Western blot, immunohistochemistry, and immunofluorescence were used to assess the location and the expression level of Gab2 in the neocortex of the temporal lobe in patients with TLE and in rat model of epilepsy. Results showed that Gab2 protein was expressed mainly in the membranes and cytoplasm of neurons in the cortex and hippocampus. Gab2 protein expression was remarkably reduced in temporal neocortex of TLE patients. In hippocampus and adjacent cortex in rat epilepsy model, Gab2 expression was decreased at different time points after kindling compared with the controls, and the lowest level of Gab2 expression occurred at 1 week. Thus, significant reductions of Gab2 protein in both TLE patients and epilepsy rats suggest that Gab2 may play an important role in the pathogenesis of TLE.

show abstract

Potential Role of Drebrin A, an F-Actin Binding Protein, in Reactive Synaptic Plasticity after Pilocarpine-Induced Seizures: Functional Implications in Epilepsy

Cited by 16 publications

References 110 publications

Differential Activation of Calpain-1 and Calpain-2 following Kainate-Induced Seizure Activity in Rats and Mice

Differential Activation of Calpain-1 and Calpain-2 following Kainate-Induced Seizure Activity in Rats and Mice

Drebrin inhibits cofilin‐induced severing of F‐actin

Decreased expression of Gab2 in patients with temporal lobe epilepsy and pilocarpine-induced rat model

Contact Info

Product

Resources

About