The expression of manganese-dependant superoxide dismutase (MnSod) in brains of sheep with neuronal ceriod lipfuscinosis: A dissertation submitted in partial fulfillment of the requirements for the Degree of Bachelor of Science with Honours

Abstract

Neuronal ceroid lipofuscinoses (NCLs, Batten disease) are a group of genetically distinct neurodegenerative diseases of children and young adults, leading to premature death and characterised by the intracellular accumulation of fluorescent lipofuscin-like (ceroid) storage bodies within lysosomes of neurons and other cell types. NCLs are the most common neurogenetic storage disease in children world-wide. Typical clinical symptoms of the disease include retinopathy leading to blindness, sleep problems, motor abnormalities, epilepsia, dementia and eventually premature death. However, mechanisms underlying these neuropathies are not fully understood. In NCLs, glial activation precedes neurodegeneration that marked by the gross atrophy, cortical thinning and neuronal loss. The neurodegeneration observed in CLN 6 defective cells and tissues could be associated with up-regulated expression of the radical scavenger MnSOD in CLN6 defective cells and tissues. A significant increase in MnSOD activity has been detected in fibroblasts and brain extracts from CLN6 sheep. The increased MnSOD levels, elevated ROS and glial inflammation have been suggested to be associated with molecular pathways in NCL pathology. The aim of this study was to investigate the regionality and cell-type selection in the change in MnSOD expression in the CLN6 and CLNS affected sheep brains. Immunohistochemical staining was used to localize MnSOD expression and distribution in the affected sheep brains. Microscopy and computational image analysis were used to examine the MnSOD stained brain region and cell morphology. The MnSOD immunoreactivity parallels the neuronal distribution in 5&6 brains. The enhanced expression of MnSOD was confined to the layer V of OCL5 and OCL6 affected sheep cerebral cortices, including the frontal, parietal and occipital lobes. Other brain regions examined did not show any marked difference in MnSOD immunoreactivity between the affected brains and the controls.

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