Drebrin A expression is altered after pilocarpine-induced seizures: time course of changes is consistent for a role in the integrity and stability of dendritic spines of hippocampal granule cells.
We used a pathophysiological model of temporal lobe epilepsy induced by pilocarpine in adult rats in order to assess the in vivo role of drebrin A (DA), one of the major regulators of F-actin. This model displays a dynamic reorganization of the glutamatergic network including neo-spinogenesis, morphogenesis, and neo-synaptogenesis associated with an aberrant sprouting of granule cell axons in the dentate gyrus (DG). This reactive plasticity contributes in dentate granule-cell hyperexcitability that could lead to the emergence of recurrent spontaneous seizures. We investigated the hippocampal DA expression changes in pilocarpine animals using immunohistochemical, Western blot, and in situ hybridization analyses. We showed that DA immunoreactivity was decreased in the inner molecular layer (IML) and in the hilus (H) of the DG, at latent stage, when spinogenesis and morphogenesis occur. Western blot analysis confirmed these overall hippocampal decreases of DA protein expression. At chronic stage, when newly formed glutamatergic synapses are being established, the levels of immunolabeling for DA in the H and the IML were similar to control rats. This recovery is likely due to the increase of DA mRNA in perikarya of hilar and granule cells. Interestingly, our data showed that the changes pattern of labeling for Bassoon, a specific marker for presynaptic active zone, in the IML of pilocarpine-treated animals paralleled those found for DA at all time points examined. Furthermore, our double and triple immunofluorescence studies showed that the recovery in DA levels in the IML occurred within the dendritic spines involved in glutamatergic active synapses of presumed granule cells. Altogether, our results indicate that in vivo DA is not critical for spinogenesis and morphogenesis but instead is consistent with an involvement in synaptic structural integrity, stabilization, and function. Thus, DA appears as a novel modulator of reactive synaptic plasticity associated with epilepsy.
CNRS, UMR6184, Neurobiologie des Interactions Cellulaires et Neurophysiopathologie (NICN), Marseille, F-13344, France.
Oualid
O
Sbai
Michel
M
Khrestchatisky
Monique
M
Esclapez
Lotfi
L
Ferhat
D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D010862:Pilocarpine / Q000506:poisoning; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
D009479:Neuropeptides; C053386:drebrins; D010862:Pilocarpine