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dc.contributor.advisorHughes, Stephanie
dc.contributor.authorPartridge, Madison
dc.date.available2017-10-29T20:14:59Z
dc.date.copyright2017
dc.identifier.citationPartridge, M. (2017). Voluntary oral dosing of cannabidiol for the treatment of Batten Disease (Thesis, Master of Science). University of Otago. Retrieved from http://hdl.handle.net/10523/7648en
dc.identifier.urihttp://hdl.handle.net/10523/7648
dc.description.abstractBatten disease, or NCL (neuronal ceroid lipofuscinosis), is a collection of 13 pathologically similar, genetically distinct, autosomal recessive, neurodegenerative lysosomal storage diseases. Primarily affecting children between the ages of 5 and 8, NCLs have an incidence of 1 in 12,500 live births and are all currently incurable and fatal. While each of the 13 forms of NCLs are genetically different, they all result in severe cortical atrophy and therefore display similar symptoms of visual impairment, seizures, behavioural and personality changes, regression in communication and motor skills and dementia, ultimately resulting in premature death in the patient’s teens to early 20s. Another common trait of the diseases is the accumulation of autofluorescent storage materials in cell lysosomes. The association between the accumulation of lysosomal storage materials and neurodegeneration is unknown, however several methods have been suggested including inflammation and apoptosis. Current treatments are only symptom based. Cannibidiol (CBD) is one of two main cannabinoids found in cannabis. The compound has been shown to have both antiepileptic and anti-inflammatory, neuroprotective properties. Unlike its other main counterpart, delta-9- tetrahydrocannabinol (Δ9-THC), CBD does not have psychoactive activity, which is known to interfere with neuronal development. These properties are desirable in the treatment of a childhood neurodegenerative disease. In this investigation, CBD was administered orally to Cln6nclf mice, a naturally occurring murine model of one form of the disease, CLN6 for a period of 4 weeks. Behavioural assessments and immunohistochemical analysis of the left thalamus, hippocampus and motor cortex of the animals was performed. Thirty-three male and female affected and unaffected animals were given daily doses of either 10 mg/kg CBD, 25 mg/kg CBD or vehicle only via voluntary oral dosing using raspberry jelly. On the second to last day of treatment, each animal performed a marble burying test followed by an elevated plus maze test. Following euthanasia and perfusion, the left hemispheres were collected and sectioned into 50 μm slices and stained and imaged for inflammatory markers glial fibrillary acidic protein (GFAP), cluster of differentiation 68 (CD68) and neuronal nitric oxide synthase (nNOS), as well as the angiogenesis marker doublecortin (DCX). Sections were also imaged for quantification of the autofluorescent material. The behavioural assessments yielded no meaningful difference between any of the treatment groups. Immunohistochemical staining and autofluorescent imaging quantification showed that while differences were detected between the affected and unaffected control animals, the treated animals did not show a significant difference from the affected control group. These results do however suggest that with prolonged treatment may yield more meaningful results. Furthermore, the weights of the animals stayed within a healthy range throughout the treatment period. The use of the sweet jelly did not enable the mice to gain weight while providing an easy, safe, convenient and tasty method of drug administration. This provides further evidence for the validity and effectiveness of voluntary oral dosing as a method of oral drug administration.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectneuronal ceroid lipofuscinosis
dc.subjectcannabidiol
dc.subjectcln6
dc.subjectnclf
dc.subjectcbd
dc.subjectBattens
dc.subjectneurodegenerative
dc.subjectBatten disease
dc.subjectvoluntary oral dosing
dc.subjectnNOS
dc.subjectGFAP
dc.subjectCD68
dc.subjectDCX
dc.subjectjelly
dc.subject10 mg/kg CBD
dc.subject25 mg/kg CBD
dc.subjectCBD
dc.titleVoluntary oral dosing of cannabidiol for the treatment of Batten Disease
dc.typeThesis
dc.date.updated2017-10-27T21:30:25Z
dc.language.rfc3066en
thesis.degree.disciplineBiochemistry
thesis.degree.nameMaster of Science
thesis.degree.grantorUniversity of Otago
thesis.degree.levelMasters
otago.openaccessOpen
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