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Involvement of brain pericyte damage in neuropathological changes | 48489

Journal of Neurology & Neurophysiology

ISSN - 2155-9562

Involvement of brain pericyte damage in neuropathological changes associated with lysosomal storage

4th International Conference and Exhibition on Neurology & Therapeutics

July 27-29, 2015 Rome, Italy

Zhou Wu

Posters-Accepted Abstracts: J Neurol Neurophysiol

Abstract :

Recent evidence suggests that peripheral blood mononuclear cells (PBMCs) contribute to the pathogenesis of
neuropathological changes in patients with neuronal ceroidlipofuscinosis (NCL) and lysosomal storage diseases. In order
to examine the possible increase in the permeability of the blood-brain-barrier (BBB) and resultant infiltration of PBMCs
due to cathepsin D (CatD) deficiency, a process underlying the onset of congenital NCL, we examined structural changes in
brain vessels in CatD-/- mice. Consequently, the mean diameter of the brain vessels in the cerebral cortex on postnatal day
24 (P24) was significantly larger in CatD-/- mice than in wild type mice. Furthermore, the mean number of brain pericytesin
CatD-/- mice began to decline significantly on P16 and almost disappeared by P24, and oxidative DNA damage was first
detected in brain pericytes on P12. Examinations with electron microscopy revealed that brain pericytes were laden with
dense granular bodies, cytoplasmic vacuoles and lipid droplets. Moreover, pepstatin A, a specific aspartic protease inhibitor,
induced mitochondria derived reactive oxygen species (ROS)production in the isolated brain pericytes, which decreased the
cell viability. These observations suggest that increased lysosomal storage due to CatD deficiency causes oxidative damage in
brain pericytes, subsequently resulting in an increased vessel diameter, enhanced permeability of the BBB and the infiltration
of PBMCs.
Recently, much attention has been paid topericytesas a novel therapeutic target for modifing disease progression in patients
with neurodegenerative disorders, such as Alzheimer’s disease. In cases of diabetic retinopathy, erythropoietin may alsobe
used as a novel therapeutic agent preventing the drop-out of pericytesfrom the retinal capillaries. Therefore, the use of agents
capable of protecting brain pericytes against oxidative damage may provide the basis for developing alternative therapies for
the treatment of neurodegenerative disorders, including NCL and Alzheimer’s disease.

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