Equine grass sickness, but not botulism, causes autonomic and enteric neurodegeneration and increases soluble N-ethylmaleimide-sensitive factor attachment receptor protein expression within neuronal perikarya

BC McGorum, S Scholes, EM Milne, SL Eaton, TM Wishart, IR Poxton, S Moss, U Wernery, T Davey, JB Harris, RS Pirie

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Reasons for performing study: Equine grass sickness (EGS) is of unknown aetiology. Despite some evidence suggesting that it represents a toxicoinfection with Clostridium botulinum types C and/or D, the effect of EGS on the functional targets of botulinum neurotoxins, namely the soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, is unknown. Further, while it is commonly stated that, unlike EGS, equine botulism is not associated with autonomic and enteric neurodegeneration, this has not been definitively assessed. Objectives: To determine: 1) whether botulism causes autonomic and enteric neurodegeneration; and 2) the effect of EGS on the expression of SNARE proteins within cranial cervical ganglion (CCG) and enteric neuronal perikarya. Study design: Descriptive study. Methods: Light microscopy was used to compare the morphology of neurons in haematoxylin-eosin stained sections of CCG and ileum from 6 EGS horses, 5 botulism horses and 6 control horses. Immunohistochemistry was used to compare the expression of synaptosomal-associated protein-25, synaptobrevin (Syb) and syntaxin within CCG neurons, and of Syb in enteric neurons, from horses with EGS, horses with botulism and control horses. The concentrations of these SNARE proteins in extracts of CCG from EGS and control horses were compared using quantitative fluorescent western blotting. Results: EGS, but not botulism, was associated with autonomic and enteric neurodegeneration and with increased immunoreactivity for SNARE proteins within neuronal perikarya. Quantitative fluorescent western blotting confirmed increased concentrations of synaptosomal-associated protein- 25, Syb and syntaxin within CCG extracts from EGS vs. control horses, with the increases in the latter 2 proteins being statistically significant. Conclusions: The occurrence of autonomic and enteric neurodegeneration, and increased expression of SNARE proteins within neuronal perikarya, in EGS but not botulism, suggests that EGS may not be caused by botulinum neurotoxins. Further investigation of the aetiology of EGS is therefore warranted.
Original languageEnglish
Pages (from-to)786 - 791
Number of pages6
JournalEquine Veterinary Journal
Volume48
Issue number6
DOIs
Publication statusFirst published - 11 Jan 2016

Fingerprint

Botulism
SNARE Proteins
Poaceae
Horses
Ganglia
R-SNARE Proteins
Synaptosomal-Associated Protein 25
Qa-SNARE Proteins
Neurotoxins
Neurons
Clostridium botulinum type D
Clostridium botulinum type C
Proteins
Western Blotting
Ethylmaleimide

Keywords

  • Botulism
  • Grass sickness
  • Horse
  • SNAP-25
  • SNARE proteins
  • Synaptobrevin
  • Syntaxin

Cite this

McGorum, BC ; Scholes, S ; Milne, EM ; Eaton, SL ; Wishart, TM ; Poxton, IR ; Moss, S ; Wernery, U ; Davey, T ; Harris, JB ; Pirie, RS. / Equine grass sickness, but not botulism, causes autonomic and enteric neurodegeneration and increases soluble N-ethylmaleimide-sensitive factor attachment receptor protein expression within neuronal perikarya. In: Equine Veterinary Journal. 2016 ; Vol. 48, No. 6. pp. 786 - 791.
@article{ab6583c2ea9749e0b35417a71dc336f5,
title = "Equine grass sickness, but not botulism, causes autonomic and enteric neurodegeneration and increases soluble N-ethylmaleimide-sensitive factor attachment receptor protein expression within neuronal perikarya",
abstract = "Reasons for performing study: Equine grass sickness (EGS) is of unknown aetiology. Despite some evidence suggesting that it represents a toxicoinfection with Clostridium botulinum types C and/or D, the effect of EGS on the functional targets of botulinum neurotoxins, namely the soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, is unknown. Further, while it is commonly stated that, unlike EGS, equine botulism is not associated with autonomic and enteric neurodegeneration, this has not been definitively assessed. Objectives: To determine: 1) whether botulism causes autonomic and enteric neurodegeneration; and 2) the effect of EGS on the expression of SNARE proteins within cranial cervical ganglion (CCG) and enteric neuronal perikarya. Study design: Descriptive study. Methods: Light microscopy was used to compare the morphology of neurons in haematoxylin-eosin stained sections of CCG and ileum from 6 EGS horses, 5 botulism horses and 6 control horses. Immunohistochemistry was used to compare the expression of synaptosomal-associated protein-25, synaptobrevin (Syb) and syntaxin within CCG neurons, and of Syb in enteric neurons, from horses with EGS, horses with botulism and control horses. The concentrations of these SNARE proteins in extracts of CCG from EGS and control horses were compared using quantitative fluorescent western blotting. Results: EGS, but not botulism, was associated with autonomic and enteric neurodegeneration and with increased immunoreactivity for SNARE proteins within neuronal perikarya. Quantitative fluorescent western blotting confirmed increased concentrations of synaptosomal-associated protein- 25, Syb and syntaxin within CCG extracts from EGS vs. control horses, with the increases in the latter 2 proteins being statistically significant. Conclusions: The occurrence of autonomic and enteric neurodegeneration, and increased expression of SNARE proteins within neuronal perikarya, in EGS but not botulism, suggests that EGS may not be caused by botulinum neurotoxins. Further investigation of the aetiology of EGS is therefore warranted.",
keywords = "Botulism, Grass sickness, Horse, SNAP-25, SNARE proteins, Synaptobrevin, Syntaxin",
author = "BC McGorum and S Scholes and EM Milne and SL Eaton and TM Wishart and IR Poxton and S Moss and U Wernery and T Davey and JB Harris and RS Pirie",
year = "2016",
month = "1",
day = "11",
doi = "10.1111/evj.12543",
language = "English",
volume = "48",
pages = "786 -- 791",
journal = "Equine Veterinary Journal",
issn = "0425-1644",
publisher = "Wiley Blackwell",
number = "6",

}

Equine grass sickness, but not botulism, causes autonomic and enteric neurodegeneration and increases soluble N-ethylmaleimide-sensitive factor attachment receptor protein expression within neuronal perikarya. / McGorum, BC; Scholes, S; Milne, EM; Eaton, SL; Wishart, TM; Poxton, IR; Moss, S; Wernery, U; Davey, T; Harris, JB; Pirie, RS.

In: Equine Veterinary Journal, Vol. 48, No. 6, 11.01.2016, p. 786 - 791.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Equine grass sickness, but not botulism, causes autonomic and enteric neurodegeneration and increases soluble N-ethylmaleimide-sensitive factor attachment receptor protein expression within neuronal perikarya

AU - McGorum, BC

AU - Scholes, S

AU - Milne, EM

AU - Eaton, SL

AU - Wishart, TM

AU - Poxton, IR

AU - Moss, S

AU - Wernery, U

AU - Davey, T

AU - Harris, JB

AU - Pirie, RS

PY - 2016/1/11

Y1 - 2016/1/11

N2 - Reasons for performing study: Equine grass sickness (EGS) is of unknown aetiology. Despite some evidence suggesting that it represents a toxicoinfection with Clostridium botulinum types C and/or D, the effect of EGS on the functional targets of botulinum neurotoxins, namely the soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, is unknown. Further, while it is commonly stated that, unlike EGS, equine botulism is not associated with autonomic and enteric neurodegeneration, this has not been definitively assessed. Objectives: To determine: 1) whether botulism causes autonomic and enteric neurodegeneration; and 2) the effect of EGS on the expression of SNARE proteins within cranial cervical ganglion (CCG) and enteric neuronal perikarya. Study design: Descriptive study. Methods: Light microscopy was used to compare the morphology of neurons in haematoxylin-eosin stained sections of CCG and ileum from 6 EGS horses, 5 botulism horses and 6 control horses. Immunohistochemistry was used to compare the expression of synaptosomal-associated protein-25, synaptobrevin (Syb) and syntaxin within CCG neurons, and of Syb in enteric neurons, from horses with EGS, horses with botulism and control horses. The concentrations of these SNARE proteins in extracts of CCG from EGS and control horses were compared using quantitative fluorescent western blotting. Results: EGS, but not botulism, was associated with autonomic and enteric neurodegeneration and with increased immunoreactivity for SNARE proteins within neuronal perikarya. Quantitative fluorescent western blotting confirmed increased concentrations of synaptosomal-associated protein- 25, Syb and syntaxin within CCG extracts from EGS vs. control horses, with the increases in the latter 2 proteins being statistically significant. Conclusions: The occurrence of autonomic and enteric neurodegeneration, and increased expression of SNARE proteins within neuronal perikarya, in EGS but not botulism, suggests that EGS may not be caused by botulinum neurotoxins. Further investigation of the aetiology of EGS is therefore warranted.

AB - Reasons for performing study: Equine grass sickness (EGS) is of unknown aetiology. Despite some evidence suggesting that it represents a toxicoinfection with Clostridium botulinum types C and/or D, the effect of EGS on the functional targets of botulinum neurotoxins, namely the soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, is unknown. Further, while it is commonly stated that, unlike EGS, equine botulism is not associated with autonomic and enteric neurodegeneration, this has not been definitively assessed. Objectives: To determine: 1) whether botulism causes autonomic and enteric neurodegeneration; and 2) the effect of EGS on the expression of SNARE proteins within cranial cervical ganglion (CCG) and enteric neuronal perikarya. Study design: Descriptive study. Methods: Light microscopy was used to compare the morphology of neurons in haematoxylin-eosin stained sections of CCG and ileum from 6 EGS horses, 5 botulism horses and 6 control horses. Immunohistochemistry was used to compare the expression of synaptosomal-associated protein-25, synaptobrevin (Syb) and syntaxin within CCG neurons, and of Syb in enteric neurons, from horses with EGS, horses with botulism and control horses. The concentrations of these SNARE proteins in extracts of CCG from EGS and control horses were compared using quantitative fluorescent western blotting. Results: EGS, but not botulism, was associated with autonomic and enteric neurodegeneration and with increased immunoreactivity for SNARE proteins within neuronal perikarya. Quantitative fluorescent western blotting confirmed increased concentrations of synaptosomal-associated protein- 25, Syb and syntaxin within CCG extracts from EGS vs. control horses, with the increases in the latter 2 proteins being statistically significant. Conclusions: The occurrence of autonomic and enteric neurodegeneration, and increased expression of SNARE proteins within neuronal perikarya, in EGS but not botulism, suggests that EGS may not be caused by botulinum neurotoxins. Further investigation of the aetiology of EGS is therefore warranted.

KW - Botulism

KW - Grass sickness

KW - Horse

KW - SNAP-25

KW - SNARE proteins

KW - Synaptobrevin

KW - Syntaxin

U2 - 10.1111/evj.12543

DO - 10.1111/evj.12543

M3 - Article

VL - 48

SP - 786

EP - 791

JO - Equine Veterinary Journal

JF - Equine Veterinary Journal

SN - 0425-1644

IS - 6

ER -