Primary dysautonomias in domestic animals: A study of neuronal protein metabolism

Pollin, Marion Mathieson (1988) Primary dysautonomias in domestic animals: A study of neuronal protein metabolism. PhD thesis, University of Glasgow.

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Abstract

Primary dysautonomia has been recognised in horses for more than 70 years, a very similar condition was first observed in cats in 1981, and recently it has also been recorded in a small number of dogs. The occurrence of this condition appears to be confined almost exclusively to Britain and parts of Scandinavia, and young adult animals are the most susceptible in each population although younger and older animals are no less severely affected if they develop the disease. In all species, cessation of gastrointestinal function is the predominant clinical finding, and the only consistent lesion demonstrable in each case is "chromatolytic" change in peripheral autonomic neurones, a finding now generally accepted as diagnostic of primary dysautonomia. The aetiology of these primary dysautonomias is unknown. This thesis examines and compares the ultrastructural lesions of peripheral autonomic neurones in cats and horses, and describes the morphological damage sustained by feline XII nucleus, spinal ventral horn and dorsal root ganglion neurones. In general, the changes in each population consist of a redistribution of rough endoplasmic reticulum, followed by loss of ribosomes from individual cistemae and distension of these cisternae by an electron-dense floccular material. This is closely related to a loss of the Golgi complex. Partial nucleolar segregation and crenation of the nuclear envelope are commonly found, and ring nucleoli are occasionally seen. Proliferated smooth endoplasmic reticulum is a frequent occurrence. Mitochondria appear relatively normal, although they are frequently denser and more slender than normal, and occasionally increased in number. Neurofilaments, tubules and lysosomes all appear relatively normal. The only major difference between the feline and equine lesions is the occurrence, in several feline peripheral autonomic neurones only, of complex smooth membranous stacks. Thiamine pyrophosphatase, an enzyme specific for 'trans' Golgi cisternae cannot be demonstrated in these stacks or any other abnormal structure in affected neurones, suggesting that if any unusual membranes are derived from the trans Golgi cisternae they do not retain their normal enzymic function. Similar results are obtained for acid phosphatase, an enzyme specific for GERL (Golgi-related Endoplasmic Reticulum producing Lysosomes) and lysosomes. Activity could only be demonstrated in lysosomes in the abnormal neurones. An examination of the in vitro incorporation of tritiated glycoprotein precursors by a slice preparation of post-mortem autonomic tissue from normal and affected horses demonstrates a great decrease in the synthetic function of affected neurones. The appearance of the dysautonomic neurones is compared to lesions resulting from specific disruption of protein synthesis at various levels in rodent dorsal root ganglia; mRNA synthesis (Adriamycin), polypeptide chain synthesis (cycloheximide), core glycosylation (tunicamycin) and terminal glycosylation and packaging within the Golgi (monensin). Based on these observed changes, together with those described in the literature of similar disruptions in various cell types, it is concluded that the primary lesion of dysautonomia occurs within the cytoplasmic components of glycoprotein synthesis (rough endoplasmic reticulum and Golgi complexes), although the precise level of damage is not yet determined. With the exception of the membranous stacks, the lesions in all the neuronal populations examined are very similar, and it is therefore extremely probable that the aetiological agent(s) in each case is also very similar, if not the same.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Veterinary science
Date of Award: 1988
Depositing User: Enlighten Team
Unique ID: glathesis:1988-76697
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 13:53
Last Modified: 19 Nov 2019 13:53
URI: http://theses.gla.ac.uk/id/eprint/76697

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