Botulinum neurotoxin type A modulates vesicular release of glutamate from satellite glial cells

Journal of Cellular and Molecular Medicine

Larissa Bittencourt da Silva¹  Jeppe Nørgaard Poulsen¹  Lars Arendt-Nielsen¹ 

[1] Center for Sensory - Motor Interaction (SMI), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg East, Denmark

关键词: botulinum neurotoxin type A;    pain;    glutamate;    vesicular release;    trigeminal ganglion;    satellite glial cells;    ionomycin;    SNAP‐25;    SNAP‐23;   

DOI  :  10.1111/jcmm.12562

来源: Wiley

【 摘 要 】

Abstract

This study investigated the presence of cell membrane docking proteins synaptosomal-associated protein, 25 and 23 kD (SNAP-25 and SNAP-23) in satellite glial cells (SGCs) of rat trigeminal ganglion; whether cultured SGCs would release glutamate in a time- and calcium-dependent manner following calcium-ionophore ionomycin stimulation; and if botulinum neurotoxin type A (BoNTA), in a dose-dependent manner, could block or decrease vesicular release of glutamate. SGCs were isolated from the trigeminal ganglia (TG) of adult Wistar rats and cultured for 7 days. The presence of SNAPs in TG sections and isolated SGCs were investigated using immunohistochemistry and immunocytochemistry, respectively. SGCs were stimulated with ionomycin (5 μM for 4, 8, 12 and 30 min.) to release glutamate. SGCs were then pre-incubated with BoNTA (24 hrs with 0.1, 1, 10 and 100 pM) to investigate if BoNTA could potentially block ionomycin-stimulated glutamate release. Glutamate concentrations were measured by ELISA. SNAP-25 and SNAP-23 were present in SGCs in TG sections and in cultured SGCs. Ionomycin significantly increased glutamate release from cultured SGCs 30 min. following the treatment (P < 0.001). BoNTA (100 pM) significantly decreased glutamate release (P < 0.01). Results from this study demonstrated that SGCs, when stimulated with ionomycin, released glutamate that was inhibited by BoNTA, possibly through cleavage of SNAP-25 and/or SNAP-23. These novel findings demonstrate the existence of vesicular glutamate release from SGCs, which could potentially play a role in the trigeminal sensory transmission. In addition, interaction of BoNTA with non-neuronal cells at the level of TG suggests a potential analgesic mechanism of action of BoNTA.

【 授权许可】

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© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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