期刊
EXPERIMENTAL NEUROLOGY
卷 335, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2020.113512
关键词
Hippocampus; dentate gyrus; dendritic spine; spine plasticity; migrating granule cells; actin cytoskeleton; alpha-actinin-2
资金
- Centre National de la Recherche Scientifique (CNRS) [UMR7051]
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Aix-Marseille University (AMU)
The study showed that the expression of alpha-actn-2 decreased during granule cell spinogenesis and morphogenesis in a rat model of chronic limbic seizures, persisting into the chronic stage when new synapses are formed. The balance between alpha-actn-2 and DA expression levels may modulate NR1 anchoring in dendritic spines.
alpha-actinin-2 (alpha-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 alpha-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 alpha-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 alpha-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, alpha-actn-2 did not protect F-actin destabilization and DA inhibited alpha-actn-2 binding to F-actin. Such alteration could affect the anchoring of NR1 in dendritic spines. Furthermore, we showed that the expression of alpha-actn-2 and NR1 are co-down-regulated in membrane fractions of pilocarpine animals at chronic stage. Last, we showed that alpha-actn-2 is expressed in migrating newly born granule cells observed within the hilus of pilocarpine-treated rats. Altogether, our results suggest that alpha-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 alpha-actn-2 and DA expression levels may modulate NR1 anchoring within dendritic spines.
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