The actin binding protein α-actinin-2 expression is associated with dendritic spine plasticity and migrating granule cells in the rat dentate gyrus following pilocarpine-induced seizures

Autor: Oualid Sbai, Lotfi Ferhat, Michel Khrestchatisky, Monique Esclapez, Rabia Soussi, Angélique Bole
Přispěvatelé: Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Khrestchatisky, Michel
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Dendritic spine
actin cytoskeleton
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
spine plasticity
Convulsants
MESH: Neuropeptides
Hippocampus
MESH: Synapses
0302 clinical medicine
Cell Movement
MESH: Convulsants
MESH: Actinin
Actinin
MESH: Animals
dentate gyrus
MESH: Neuronal Plasticity
Receptor
MESH: Cell Movement
Neuronal Plasticity
biology
dendritic spine
Chemistry
α-actinin-2
Pilocarpine
Cell migration
MESH: Seizures
Cell biology
medicine.anatomical_structure
Neurology
MESH: Receptors
GABA
MESH: Rats
Dendritic Spines
Neurogenesis
MESH: Actins
MESH: Dendritic Spines
03 medical and health sciences
Developmental Neuroscience
Receptors
GABA
Seizures
medicine
Animals
Actin-binding protein
Rats
Wistar
Actin
Dentate gyrus
Neuropeptides
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
MESH: Rats
Wistar
Actin cytoskeleton
Granule cell
Actins
MESH: Male
MESH: Pilocarpine
Rats
MESH: Neurogenesis
030104 developmental biology
Synapses
biology.protein
migrating granule cells
030217 neurology & neurosurgery
MESH: Dentate Gyrus
Zdroj: Experimental Neurology
Experimental Neurology, 2021, 335, pp.113512. ⟨10.1016/j.expneurol.2020.113512⟩
ISSN: 0014-4886
1090-2430
Popis: International audience; α-actinin-2 (α-actn-2) is an F-actin-crosslinking protein, localized in dendritic spines. In vitro studies suggested that it is involved in spinogenesis, morphogenesis, actin organization, cell migration and anchoring of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptors in dendritic spines. However, little is known regarding its function in vivo. We examined the levels of α-actn-2 expression within the dentate gyrus (DG) during the development of chronic limbic seizures (epileptogenesis) induced by pilocarpine in rats. In this model, plasticity of the DG glutamatergic granule cells including spine loss, spinogenesis, morphogenesis, neo-synaptogenesis, aberrant migration, and alterations of NMDA receptors have been well characterized. We showed that α-actn-2 immunolabeling was reduced in the inner molecular layer at 1-2 weeks post-status epilepticus (SE), when granule cell spinogenesis and morphogenesis occur. This low level persisted at the chronic stage when new functional synapses are established. This decreased of α-actn-2 protein is concomitant with the recovery of drebrin A (DA), another actin-binding protein, at the chronic stage. Indeed, we demonstrated in cultured cells that in contrast to DA, α-actn-2 did not protect F-actin destabilization and DA inhibited α-actn-2 binding to F-actin. Such alteration could affect the anchoring of NR1 in dendritic spines. Furthermore, we showed that the expression of α-actn-2 and NR1 are co-down-regulated in membrane fractions of pilocarpine animals at chronic stage. Last, we showed that α-actn-2 is expressed in migrating newly born granule cells observed within the hilus of pilocarpine-treated rats. Altogether, our results suggest that α-actn-2 is not critical for the structural integrity and stabilization of granule cell dendritic spines. Instead, its expression is regulated when spinogenesis and morphogenesis occur and within migrating granule cells. Our data also suggest that the balance between α-actn-2 and DA expression levels may modulate NR1 anchoring within dendritic spines.
Databáze: OpenAIRE
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