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

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.

Histological assessment of β‐amyloid precursor protein immunolabelled rectal biopsies aids diagnosis of equine grass sickness

“…Accumulation of b-APP in the perikarya and intraganglionic axons, but not in larger nerve fascicles, is consistent with the last of these options. Consistent with the latter two hypotheses, ultrastructural loss of a recognisable Golgi structure is a likely early event in EGS, and EGS is associated with major perturbations in the cytoskeleton of autonomic neurons that result in the accumulation of dopamineb-hydroxylase and presynaptic proteins in neuronal perikarya [19,27,28]. b-APP has been described as a marker of early axonal injury prior to apparent histological changes in routine H&E-stained sections [29].…”

Equine grass sickness: Benefits of a multifaceted research approach

“…In this issue of EVJ, the study by McGorum et al [20] confirms the absence of autonomic and enteric neurodegeneration in equine botulism, thus highlighting pathological differences between this disease and EGS. shaker foal syndrome), both of which ultimately result in profound neuroparalysis irrespective of the site of toxin liberation (feed or gastrointestinal tract).…”

“…Furthermore, the autonomic and enteric neurodegeneration that typify EGS are not recognised features of neuroparalytic botulism. In this issue of EVJ, the study by McGorum et al [20] confirms the absence of autonomic and enteric neurodegeneration in equine botulism, thus highlighting pathological differences between this disease and EGS. Additionally, molecular techniques were used to demonstrate both an increased immunoreactivity for SNARE proteins (functional targets of botulinum neurotoxins) within autonomic neuronal perikarya and a significantly greater concentration of the SNARE proteins, synaptobrevin and syntaxin, within autonomic ganglia of EGS, but not botulism cases, compared with control horses.…”

Secreted Chaperones in Neurodegeneration

“…The idea that proSAAS plays a role in neurodegenerative proteostasis is further supported by human transcriptomics studies, which indicate increased proSAAS expression during AD progression ( Mathys et al, 2019 ). Increased levels of proSAAS have also been found in brain tissues of patients with CAA ( Inoue et al, 2017 ), as well as in models of neurodegenerative diseases including horses ( McGorum et al, 2016 ) and rats ( Chatterji et al, 2014 ). Lastly, recent data from our laboratory indicate that cellular proSAAS levels are upregulated following ER and even heat stress ( Shakya et al, 2020 ); interestingly, in parallel experiments, similar upregulation was not observed for 7B2.…”