ORCID Profile
0000-0002-2299-8399
Current Organisation
University of Technology Sydney
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Publisher: Cold Spring Harbor Laboratory
Date: 25-07-2022
DOI: 10.1101/2022.07.25.501480
Abstract: Cognitive-behavioural testing in preclinical models of Alzheimer’s disease has typically been limited to visuo-spatial memory tests and has failed to capture the broad scope of deficits patients also display in goal-directed action control. The current study addresses this gap by providing the first comprehensive investigation of how goal-directed actions are affected in a transgenic mouse model of Alzheimer’s disease. Specifically, we tested outcome devaluation performance – a popular test of goal-directed action – in male and female human amyloid precursor protein (hAPP)-J20 mice. Mice were first trained to press a left and right lever for unique pellet and sucrose outcomes respectively (counterbalanced) over four days. On test, mice were fed one of the two outcomes to reduce its value via sensory specific satiety and subsequently given a choice between levers. Goal-directed action was intact for 36-week-old wildtype mice of both sexes, because they responded more on the lever associated with the still-valued outcome than that associated with the devalued outcome (i.e. Valued Devalued). Goal-directed action was impaired (Valued = Devalued) for J20 mice of both sexes, and for 52-week-old male mice regardless of genotype. Following an additional 4 days of lever press training (i.e., 8 days lever pressing in total), outcome devaluation was intact for all mice regardless of age or genotype. Immunohistochemical analysis revealed that increased microglial expression in the dorsal CA1 region of the hippoc us was associated with poorer outcome devaluation performance on initial tests, but not with tests performed after 8 days of lever pressing. Together, these data demonstrate that goal-directed action is transiently impaired in J20 mice of both sexes and in aging male mice regardless of genotype, and that this impairment is related to neuroinflammation in the dorsal CA1 region of the hippoc us.
Publisher: ClinMed International Library
Date: 31-12-2014
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.NLM.2018.08.001
Abstract: The common polymorphism rs17518584, near the cell adhesion molecule 2 gene (CADM2), was previously identified as playing a role in information processing speed in a genome-wide association study of executive functions and processing speed performed in a cohort of non-demented older adults. In this study, we investigated this polymorphism in a younger population cohort (≤30 years old, median age 19 years), with no known memory or psychiatric disorders, for which we had phenotyped all participants for memory function (n = 514), and a subset of the participants for executive functions (n = 338), using a battery of tests measuring visuo-spatial memory, working memory, verbal memory, and frontal lobe functions (visual scanning, graphomotor speed, and cognitive flexibility). The polymorphism rs17518584 was genotyped by a restriction fragment length polymorphism assay and analysis indicated that the CADM2 polymorphism showed evidence of association with information processing speed as inferred from scores from the Stroop Word, Colour, and Colour-Word Tests (p = 0.005, p = 0.04, and p = 0.028, respectively, in a dominant inheritance model), as well as Trail Making Test Part A (p = 0.005 in an additive model). Significant associations of rs17518584 with scores from other tests of memory subtypes were not detected. The findings of this study provide further support for a role of CADM2 in aspects of cognitive function, in particular reading and information processing speed, and suggest that this role extends to younger in iduals.
Publisher: Springer Science and Business Media LLC
Date: 17-07-2019
Publisher: MDPI AG
Date: 17-03-2017
DOI: 10.3390/IJMS18030655
Publisher: Springer Science and Business Media LLC
Date: 23-06-2016
Publisher: Wiley
Date: 19-06-2020
DOI: 10.1002/JNR.24666
Publisher: Frontiers Media SA
Date: 16-05-2017
Location: Australia
No related grants have been discovered for Nesli Avgan.