Thesis

FXYD6 : impact on working memory and brain activity

Creator
Awarding institution
  • University of Strathclyde
Date of award
  • 2015
Thesis identifier
  • T13957
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • There is emerging evidence that the FXYD6 gene is a risk gene for the neuropsychiatric disorder - schizophrenia. The encoded protein - phosphohippolin has been shown to be highly expressed within the prefrontal cortex and hippocampus which are brain regions that are involved in learning and memory. Lesions within these regions have been shown to impair spatial learning. Therefore an investigation of the neurobiology of this risk gene will be helpful in determining the involvement it may have on working memory. The FXYD6 transgenic mice were tested in the radial arm maze (RAM) behavioural task in the aim to examine if these knock-out (KO) animals display any working memory (WM) deficits in comparison to the wild-type (WT) counterparts. The RAM works under a computer-operated system and the number of incorrect arm entries relates to a WM impairment. Overall the KO mice show a minimal impairment in WM in the behavioural task. A genotype significance was demonstrated in the less challenging n-back levels. A second mechanism was implicated as a further challenge to the mice with the use of ketamine an N-methyl-D-aspartate receptor (NMDAR) antagonist at a subanaesthetic dose of 10, 20 and 30mg/kg intraperitoneally. The WT and KO animals show a modest effect with ketamine and a genotype significance was only demonstrated at the dose of 20mg/kg of ketamine. The effects on brain activity were analysed with the use of ¹⁴C-2-deoxyglucose (2-DG) autoradiography. The resulting data portrayed significant effects with the ketamine treatment in 50% of the region of interests (RoIs) analysed and a genotype effect was detected in the thalamic nuclei - ventral reticular thalamus. There seems to be a modest effect on WM in the RAM in both the WT and KO animals whereas resulting data from the autoradiographic brain analysis indicate that there are slight alterations in brain activity under the influence of ketamine.
Resource Type
DOI
Date Created
  • 2015
Former identifier
  • 1217352

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