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  • The Long-Term Pannexin 1 Ablation Produces Structural and Functional Modifications in Hippocampal Neurons.

The Long-Term Pannexin 1 Ablation Produces Structural and Functional Modifications in Hippocampal Neurons.

Cells (2022-11-27)
Carolina Flores-Muñoz, Francisca García-Rojas, Miguel A Pérez, Odra Santander, Elena Mery, Stefany Ordenes, Javiera Illanes-González, Daniela López-Espíndola, Arlek M González-Jamett, Marco Fuenzalida, Agustín D Martínez, Álvaro O Ardiles
ABSTRACT

Enhanced activity and overexpression of Pannexin 1 (Panx1) channels contribute to neuronal pathologies such as epilepsy and Alzheimer's disease (AD). The Panx1 channel ablation alters the hippocampus's glutamatergic neurotransmission, synaptic plasticity, and memory flexibility. Nevertheless, Panx1-knockout (Panx1-KO) mice still retain the ability to learn, suggesting that compensatory mechanisms stabilize their neuronal activity. Here, we show that the absence of Panx1 in the adult brain promotes a series of structural and functional modifications in the Panx1-KO hippocampal synapses, preserving spontaneous activity. Compared to the wild-type (WT) condition, the adult hippocampal neurons of Panx1-KO mice exhibit enhanced excitability, a more complex dendritic branching, enhanced spine maturation, and an increased proportion of multiple synaptic contacts. These modifications seem to rely on the actin-cytoskeleton dynamics as an increase in the actin polymerization and an imbalance between the Rac1 and the RhoA GTPase activities were observed in Panx1-KO brain tissues. Our findings highlight a novel interaction between Panx1 channels, actin, and Rho GTPases, which appear to be relevant for synapse stability.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Pannexin-1/PANX1 Antibody, from rabbit, purified by affinity chromatography
Sigma-Aldrich
Anti-Post Synaptic Density Protein 95 Antibody, clone 6G6-1C9, clone 6G6-1C9, Chemicon®, from mouse