Interneuronal Transfer and Distal Action of Tetanus Toxin and Botulinum Neurotoxins A and D in Central Neurons.

Abstract:

:Recent reports suggest that botulinum neurotoxin (BoNT) A, which is widely used clinically to inhibit neurotransmission, can spread within networks of neurons to have distal effects, but this remains controversial. Moreover, it is not known whether other members of this toxin family are transferred between neurons. Here, we investigate the potential distal effects of BoNT/A, BoNT/D, and tetanus toxin (TeNT), using central neurons grown in microfluidic devices. Toxins acted upon the neurons that mediated initial entry, but all three toxins were also taken up, via an alternative pathway, into non-acidified organelles that mediated retrograde transport to the somato-dendritic compartment. Toxins were then released into the media, where they entered and exerted their effects upon upstream neurons. These findings directly demonstrate that these agents undergo transcytosis and interneuronal transfer in an active form, resulting in long-distance effects.

journal_name

Cell Rep

journal_title

Cell reports

authors

Bomba-Warczak E,Vevea JD,Brittain JM,Figueroa-Bernier A,Tepp WH,Johnson EA,Yeh FL,Chapman ER

doi

10.1016/j.celrep.2016.06.104

subject

Has Abstract

pub_date

2016-08-16 00:00:00

pages

1974-87

issue

7

issn

2211-1247

pii

S2211-1247(16)30927-5

journal_volume

16

pub_type

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