NP3D Flashcards
in this condition, the cerebellum forms normally, but then we begin to see progressive signs of cerebellar dysfunction between birth and nine months of age. (shown to follow an autosomal recessive mode of inheritance)
Cerebellar abiotrophy
degeneration or loss of function or vitality in an organism or in cells or tissues not due to any apparent injury
abiotrophy
Cerebellar abiotrophy: in the dog, the genetic change disrupts function of a protein known as __________
Parkin, directs abnormal proteins in the cell to the proteasome for degradation
Cerebellar abiotrophy: The expression of this defect is surprising in that the _____________ is the primary organ affected
cerebellum
Cerebellar abiotrophy: ___________ is the basis for a definitive diagnosis, showing selective necrosis of Purkinje cells, with secondary thinning of the molecular cell layer and loss of cellularity in the internal granular cell layer
Histology
The changes do not cause a notable reduction in size of the cerebellum except in more severe forms, and then it generally requires a more quantitative analysis of MRI data
Cerebellar abiotrophy
clinical signs are progressive from birth
cerebellar abiotrophy
clinical signs do not progress
cerebellar hypoplasia
Histologically: we see necrotic Purkinje cells and no evidence of dysplasia
abiotrophy
Histologically: cells are simply missing and the tissue is disorganized (dysplastic)
hypoplasia
Lysosomal storage disorders:
A defect in the _________ will result in a more dramatic accumulation of the enzyme’s substrate and this is associated with a more rapid progression of clinical neurological disease
active site
Lysosomal storage disorders:
Defects in the _________ will have lesser effects on overall enzyme function and will be associated with a slower progression of disease.
regulatory site
Lysosomal storage disorders: Defects follow an autosomal recessive mode of inheritance. Clinical disease is expressed in _______
homozygotes
What is it about lysosomal storage that creates problems?
- Accumulated material may be directly toxic to the cell, or metabolites from alternate catabolic pathways may be toxic to the cell.
- Accumulated material may be a physical impediment to neuronal axoplasmic transport.
Diagnosing a lysosomal storage disorder:
- diagnosis can be made antemortem
- treated with gene replacement therapy, bone narrow transplant
- classified according to the material that accumulates as a consequence of the enzyme deficiency: lipidosis, glycoproteinosis, and mucopolysaccharidosis. There are multiple specific enzyme defects that can give rise to a lipidosis, glycoproteinosis or mucopolysaccharidosis.
disease in a cat, which is a sphingolipidosis
Niemann-Pick
a unique type of neuron-specific to the cerebellar cortex
Purkinje cell
Storage disorders can also be acquired:
Unfortunately, nobody agrees on the dose of chloroquine for penguins and the levels used here were excessive. Fortunately, lesions are reversible and the chloroquine dose was adjusted for the surviving penguins and they subsequently recovered
Acquired _____________ are observed in herbivores following ingestion of certain plants
glycoproteinoses
lysosomal storage diseases affecting glycoproteins, resulting from defects in lysosomal function
glycoproteinoses
There is one storage disorder that is classified as a ____________
proteinosis
the accumulation of abnormal amounts of protein in bodily tissues (in the cytoplasm)
proteinosis
This is not a lysosomal storage disease, but rather a defect in protein and lipid trafficking within the cell (in some ways similar to what we discussed in cerebellar abiotrophy). But instead of dying, the cells accumulate aggregates of protein and lipid that are highlighted with a special stains (acid-fast, in which granules attain a purplish-red), giving rise to a more protracted loss of function. Microscopic examination of tissues using a UV light source also shows the inclusions to autofluorescence yellow – the definitive diagnosis is easy to make.
ceroid lipofuscinosis
Niemann-Pick also affects Schwann cells in the ___________, resulting in a polyneuropathy. Illustrated is loss of myelin, collapse of the Schwann cell-associated endoneurium, and accumulation of lipid-laden phagocytes
periphery
