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Neuronal Ceroid Lipofuscinosis
Neuronal Ceroid Lipofuscinosis
Neuronal Ceroid Lipofuscinosis
Ceroid Lipofuscinosis (NCL). Black scale bars represent 20m, while the
white scale bar in the inset represents 250nm (Abitbol, 2010).
Of the two slides shown above, the left is non-diseased and the right is the
diseased. There is an obvious difference in the composition of the two
slides, the normal tissue showing orderly layering and segregation of cells.
From the spongy pink matter in the upper left corner to the diagonal line
of circular shaped cells of a deeper pink and lastly to the dense purple
granulate material in the bottom right hand corner. The diseased tissue
has none of this order and fewer of the circular shaped cells. This shows
that the disease seems to disrupt the organisation of these organelles.
Lipofuscin usually appears brown under the light microscope, but stains
pink with Periodic Acid-Schiff stain, since lipofuscin is composed of crosslinked protein residues (Brunk & Terman, 2002) and protein and
carbohydrate is stained pink with PAS (Pernik, 2015). The full stain for
these images is therefore PAS and hematoxylin.
Accumulation of lipofuscin within the cell is a key symptom of NCL, where
the dysfunction of sphingolipid metabolism causes accumulation of
lipofuscin (Persaud-Sawin, et al., 2007). Lipofuscin further interferes with
homeostasis of the cell and eventually causes degradation and then
apoptosis of Purkinje cells (Abitbol, 2010), indicating that the Purkinje cells
in Figure 1D are dying. While several different strains of the disease exist
across species and breeds, neither the ultrastructure of the lipofuscin nor
the histological appearance of the disease can be used to reliably identify
the particular strain (Vandevelde & Fatzer, 1980). It can therefore be
concluded that NCL in American Staffordshire Terriers is characterised by
abnormal accumulation of membranous lipofuscin within the cytoplasm of
Purkinje cells in the cerebellar cortex, which causes their degradation and
loss.
Figure 6: Electron micrograph of lipofuscin in the Purkinje cells of a 15year-old dwarf lemur. Lipid droplets are identified by the letters 'Li', while
pigment granules are identified by a white arrow. Obtained by TEM,
87,250x magnification (Gilissen & Staneva-Dobrovski, 2013).
Lysosomes:
An organelle which is closely associated with Neuronal Ceroid
Lipofuscinosis (Battens Disease) is the lysosome. The disease is caused
by an abnormal build-up of the lipopigment lipofuscin inside the organelle
(lysosome) and promotes cell senescence (Jalanko & Braulke, 2009).
Unregulated cell death within neural areas is of particular concern as it
leads to neurological impairment. Lysosomes exhibit two main forms;
primary and secondary. The primary lysosomes are the resultant of a
budding from the Golgi apparatus. The secondary lysosomes are formed
when primary lysosomes bind to a vesicle and breaks down the material
encased in the vesicle. Lysosomes are encased by a phospholipid bilayer
which assists in containing the various digestive enzymes within (Ivy Rose,
2015). Lysosomes function to enzymatically digest material both up taken
from the external of the cell and expired cellular components within the
cell (BSCB, 2016). These enzymes which speed up degradation are
predominantly acid hydrolases (i.e. lipases, phosphatases) which function
at a slightly acidic pH of approx. 5 (Tammen, 2016). Lysosomes are
responsible for the degradation and recycling of a variety of cellular
materials. These come from 3 main sources; material taken into the cell
via endocytosis, material taken in via phagocytosis and thirdly, expired
material inside the cell taken in by autophagosomes. It has been
evidenced that the lysosome is not an independent organelle and requires
collaboration with late endosomes in order to digest material (BSCB,
2016). As aforementioned, lysosomes play an integrated role with other
cellular components in order to recycle and digest cellular material.
Lysosomes, or lysosomal complexes are often the final destination in
many secretory pathways following exocytosis. Their coordination with
late endosomes is essential for normal cellular function as the acid
hydrolases contained within the lysosome break down the material
provided by the endosome (Tammen, 2016).
References
Abitbol, M., 2010. A canine Arylsulfatase G (ARSG) mutation leading to a
sulftase deficiency is associated with neuronal ceroid lipofuscinosis.
Proceedings of the National Academy of Sciences of the United States of
America (PNAS), 17 August, 107(33), pp. 14775-14780.
Brunk, U. & Terman, A., 2002. Lipofuscin: mechanisms of age-related
accumulation and influence on cell function. Free Radical Biology and
Medicine, 1 September, 33(5), pp. 611-619.
Fischer, A., Jacobson, K. & Rose, J. Z. R., 2008. Hematoxylin and eosin
staining of tissue and cell sections. Cold Spring Harbor Protocols, 1 May, p.
4986.
Gilissen, E. & Staneva-Dobrovski, L., 2013. Distinct Types of Lipofusci
PIgment in the Hippocampus and Cerebellum of aged Cheirogaleid
Primates. The Anatomical Record, Issue 296, pp. 1895-1906.
Lysosome, British Society for Cell Biology, viewed 1st April 2016
<bscb.org/learning-resource/softcell-e-learning/lysosome/>
Olsen, MOJ, 2015, Nucleolus: Structure and Function Rosalind Franklin
Univrersity of Medicine and Science, North Chicago, Illinois, USA 2015,
Online Edition
Tammen, I 2016, Cytology 2, lecture notes distributed in the Unit of
Study VETS1032 Animal Energetics & Homeostasis, University of Sydney,
Camperdown on March 3rd
Tammen, I 2016, Cytology 3, lecture notes distributed in the Unit of
Study VETS1032 Animal Energetics & Homeostasis, University of Sydney,
Camperdown on March 3rd
Tammen, I 2016, Cytology 4, lecture notes distributed in the Unit of
Study VETS1032 Animal Energetics & Homeostasis, University of Sydney,
Camperdown on March 8th
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Jalanko, A. and Braulke, T., 2009. Neuronal ceroid
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Santavuori, P., 1988. Neuronal ceroid-lipofuscinoses in childhood. Brain
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