Metabolic impairment of the posterior cingulate cortex and reversal by methylene blue: a novel model and treatment of early stage Alzheimer's disease

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dc.contributor.advisorGonzalez-Lima, Francisco, 1955-en
dc.creatorRiha, Penny Denise, 1975-en
dc.date.accessioned2008-08-29T00:02:06Zen
dc.date.accessioned2017-05-11T22:18:56Z
dc.date.available2008-08-29T00:02:06Zen
dc.date.available2017-05-11T22:18:56Z
dc.date.issued2007-12en
dc.description.abstractAlzheimer's disease (AD) is associated with decreased brain energy metabolism. Hypometabolism in the posterior cingulate cortex (PCC) occurs before the onset of memory deficits in subjects at genetic risk for AD who are not yet cognitively impaired. There is a specific inhibition in cytochrome oxidase (C.O.) in the PCC, an area involved in spatial navigation. Creating an animal model that exhibits the early pathophysiology of AD is important for developing and testing drugs that could reverse memory problems associated with such deficits. Methylene blue (MB) is a compound that improves C.O. activity and memory retention in rats. This dissertation had three specific aims: 1) to examine if isolated PCC hypometabolism causes spatial memory deficits in rats; 2) to find a dose of MB that improves memory without nonspecific behavioral effects; and 3) to prevent memory deficits from PCC hypometabolism with low dose MB. PCC hypometabolism was produced by focal administration of sodium azide, an inhibitor of C.O. activity. PCC hypometabolism resulted in impaired spatial memory in a hole board food-search task, increased oxidative damage, and neurotoxicity in the PCC. In addition, PCC hypometabolism resulted in reduced inter-regional correlations in brain activity. Our second set of studies examined the dose-response effects of MB. Our findings demonstrated that a low dose of MB: 1) enhanced memory in open field habituation and object recognition tasks; 2) did not affect general locomotor activity, exploration, motivation, or anxiety; and 3) increased brain oxygen consumption 24 hr after in vivo administration. Finally, our last study found that low dose MB prevented the deficits caused by PCC hypometabolism. MB did not prevent PCC inhibition or cell loss caused by sodium azide. Inter-regional correlations of brain metabolic activity suggested that rats treated with MB were using a different, but equally efficient, strategy for memory retrieval. This animal model of C.O. hypometabolism in the PCC can provide information to understand the mechanisms that regulate early pathological degeneration and reveal new therapeutic strategies aimed at reducing or preventing cognitive decline. Studies of low dose MB in humans are needed to examine its effects in AD patients.en
dc.description.departmentPsychologyen
dc.format.mediumelectronicen
dc.identifier.oclc212150405en
dc.identifier.urihttp://hdl.handle.net/2152/3663en
dc.language.isoengen
dc.rightsCopyright © is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works.en
dc.subject.lcshMethylene blue--Therapeutic useen
dc.subject.lcshAlzheimer's disease--Treatmenten
dc.subject.lcshMemory--Effect of drugs onen
dc.subject.lcshBrain--Metabolismen
dc.subject.lcshMemory disordersen
dc.titleMetabolic impairment of the posterior cingulate cortex and reversal by methylene blue: a novel model and treatment of early stage Alzheimer's diseaseen
dc.title.alternativeNovel model and treatment of early stage Alzheimer's diseaseen
dc.type.genreThesisen

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